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We previously found relationships between body condition and physiological function affecting health and welfare of female tourist camp elephants in Thailand, and used that approach to conduct a similar study of bull elephants in the same camps (n = 13). A body condition score (BCS) was done every other month, and fecal glucocorticoid metabolite (FGM) concentrations were measured twice monthly for 1 year. Effects of season, camp management and tourist activity on lipid profiles [total cholesterol (TC), low density lipoproteins (LDL), high density lipoproteins (HDL), triglycerides (TG)] and metabolic factors [insulin, glucose, fructosamine, glucose to insulin ratio (G:I)] were determined and correlated to measures of body condition, testosterone and FGM. Positive correlations were found between BCS and TG, between FGM and TG, HDL and glucose, and between testosterone and HDL, whereas BCS and testosterone were negatively associated with the G:I. There was a significant positive relationship between FGM and testosterone. Elevated FGM concentrations were associated with altered lipid and metabolic profiles and were higher in winter compared to summer and rainy seasons. Insulin and glucose levels were higher, while the G:I was lowest in the winter season. Strong positive associations were found between TC and HDL, LDL and HDL and glucose, and glucose and insulin. By contrast, negative relationships were found between the G:I and HDL and glucose, and between insulin and G:I. Differences also were found between High and Low tourist season months for FGM, insulin, and G:I. Last, there was notable variation among the camps in measured parameters, which together with tourist season effects suggests camp management may affect physiological function and welfare; some negatively like feeding high calorie treats, others positively, like exercise. Last, compared to females, bull elephants appear to be in better physical health based on normal BCSs, lower insulin levels and higher G:I ratios. | [
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] |
OBJECTIVES: Undergraduate medical students experience a considerable amount of stress and anxiety due to frequent exams. The goal of the present study was to examine the development of exam related anxiety and to test for a correlation between anxiety and learning approaches.METHODS: A whole class of 212 medical students was invited to participate in the study. During their first term, trait anxiety and learning approaches were assessed by use of the state-trait-anxiety inventory (STAI-T) and the approaches-and-study-skills-inventory-for-students (ASSIST), respectively. Acute state anxiety was assessed twice in the course of the second term. To that extent, the STAI-S in combination with measuring salivary cortisol were employed immediately before two oral anatomy exams.RESULTS: Our most important results were that a surface learning approach correlated significantly with anxiety as a trait and that students with a predominantly strategic approach to learning were the least anxious yet academically most successful.CONCLUSION: As surface learners are at risk of being academically less successful and because anxiety is a prerequisite for burn-out, we suggest that medical faculties place particular emphasis on conveying strategies for both, coping with stress and successful learning. | [
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A new species, Manglietia pubipedunculata Q. W. Zeng & X. M. Hu (Magnoliaceae) is described and illustrated from Yunnan, China. In addition to macromorphological examination, we comparatively studied on micromorphology of leaf epidermis, leaf structure, and epidermal cell on the sclerotesta. This new species is similar to M. kwangtungensis in terms of having dense pubescence, however, their pubescence are quite different. Manglietia pubipedunculata has appressed, compressed, shorter and sparser pubescence consisting of single or two cells. Moreover, it differs from M. kwangtungensis by showing shorter and thicker peduncles, longer styles, basal carpels covered with sparsely brown appressed pubescence, and more ovules per carpel. Furthermore, the new species has thinner leaves, brown and rugged surfaces on sclerotesta, and the alveolate cell pattern consisting of pentagon or hexagon cells with papilla on secondary cell wall under the observation by SEM. The phylogenetic analysis from two nuclear PHYA and LEAFY and chloroplast trnH-psbA sequences of 11 taxa reveals that M. pubipedunculata is a distinct species. | [
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The threat of invasive plant species in island populations prompts the need to better understand their population genetics and dynamics. In the Galapagos islands, this is exemplified by the introduced guava (Psidium guajava), considered one of the greatest threats to the local biodiversity due to its effective spread in the archipelago and its ability to outcompete endemic species. To better understand its history and genetics, we analyzed individuals from three inhabited islands in the Galapagos archipelago with 11 SSR markers. Our results reveal similar genetic diversity between islands, and the populations appear to be distinct: the islands of San Cristobal and Isabela are genetically different while the population of Santa Cruz is a mixture from both. Additional evidence for genetic bottlenecks and the inference of introduction events suggests an original introduction of the species in San Cristobal, from where it was later introduced to Isabela, and finally into Santa Cruz. Alternatively, a second introduction in Isabela might have occurred. These results are contrasted with the historical record, providing a first overview of the history of P. guajava in the Galapagos islands and its current population dynamics. | [
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] |
We propose a new sparsification method for the singular value decomposition-called the constrained singular value decomposition (CSVD)-that can incorporate multiple constraints such as sparsification and orthogonality for the left and right singular vectors. The CSVD can combine different constraints because it implements each constraint as a projection onto a convex set, and because it integrates these constraints as projections onto the intersection of multiple convex sets. We show that, with appropriate sparsification constants, the algorithm is guaranteed to converge to a stable point. We also propose and analyze the convergence of an efficient algorithm for the specific case of the projection onto the balls defined by the norms L1 and L2. We illustrate the CSVD and compare it to the standard singular value decomposition and to a non-orthogonal related sparsification method with: 1) a simulated example, 2) a small set of face images (corresponding to a configuration with a number of variables much larger than the number of observations), and 3) a psychometric application with a large number of observations and a small number of variables. The companion R-package, csvd, that implements the algorithms described in this paper, along with reproducible examples, are available for download from https://github.com/vguillemot/csvd. | [
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BACKGROUND: Molecular typing and whole genome sequencing (WGS) information is used for (inter-) national outbreak investigations. To assist the implementation of these techniques for tuberculosis (TB) surveillance and outbreak investigations at European level there is a need for inter-country collaboration and standardization. This demands more information on molecular typing practices and capabilities of individual countries. We aimed to review the use of molecular/genomic typing for TB surveillance in European Union and European Economic Area countries in 2016; assess its public health value; and collect experiences on typing data use for cross-border cluster investigations.METHOD: A web-based questionnaire was provided to all TB National Focal Points. The questionnaire consisted of three parts: i) Use and integration of molecular and genomic typing data into TB surveillance; ii) Cross-border cluster investigation and international collaboration, and iii) Perception and evaluation of public health benefits of molecular and genomic typing for TB surveillance.RESULTS: Of 26 responding countries, 20 used molecular typing for TB surveillance, including nine applying WGS. The level of integration into the national surveillance was heterogeneous. Among six countries not using typing for TB surveillance, more than half planned its implementation soon. Overall, most countries perceived an added public health value of molecular typing for TB control. Concerning international cluster investigations, countries had little experience and did not have standard protocols to exchange typing data.CONCLUSION: Our study shows a wide use of molecular and genomic typing data for TB surveillance in EU/EEA countries and reveals that transition to WGS-based typing is ongoing or is considered in most countries. However, our results also show a high heterogeneity in the use and integration of typing data for TB surveillance. Standardization of typing data use for TB surveillance is needed and formal procedures should be developed to facilitate international collaboration. | [
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BACKGROUND: Whole body vibration exercise (WBVE) has been shown to improve muscular strength and power, and increase peripheral blood flow. The aim of this study was to evaluate the behavior of the skin temperature (Tsk) on regions of the lower limbs from an acute bout of WBVE.METHODS AND FINDINGS: Cross-sectional study approved by local ethics committee (Certificado de Apresenta??o para Aprecia??o ?tica-CAAE-19826413.8.0000.5259) and Trial registration (Registro Brasileiro de Ensaios Cl?nicos-REBEC-RBR-738wng). Using Infrared thermography (IRT), Tsk and thermal symmetry of the posterior lower extremities (thigh, knee, calf and heel) were examined in 19 healthy participants. IRT was assessed during 60-second WBVE exposures of 0, 30 and 50 Hz. From the adjusted linear mixed effects model, vibration frequency, time and regions of the lower extremity were significant (p<0.001). However, the variable laterality was not significant (p = 0.067) and was excluded from the adjusted statistical model. The adjusted model was significant (p<0.00001) and all variables in the model were significant (p<0.01) indicating that Tsk decreases with time, independently of the vibration frequency. The value of the Pseudo-R-Squared for the model was 0.8376. The presented mathematical model of the current study may be useful to justify the patterns observed for all vibration frequencies between and 0 and 50 Hz. The main limitations of the study were the reduced time of the intervention and not having evaluated other regions of the body.CONCLUSIONS: The acute exposure of 60-second mechanical vibration has effect on the behavior of Tsk of the posterior region of the lower limbs, which is likely to be associated with a decrease on the blood flow due to WBVE. It is speculated that during WBVE a greater supply of blood is required where the body responds by shunting blood flow from the skin to working muscle in the first seconds of exercise. Further investigative work is required to verify this hypothesis. | [
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In recent years, most countries around the world have faced increasing pressures in the realm of emergency management than ever before. Medical service organization selection is one of the most vital facets of emergency management. Meanwhile, during the selection process, many criteria may conflict with one another and information is uncertain, rendering decision-making processes complex. Hence, multi-objective optimization, fuzzy way and stochastic theories serve as suitable means of addressing such problems. In this paper, a fuzzy multi-objective linear model is developed to overcome medical service organization selection issues and uncertain information. Meanwhile, a fuzzy objective and weight are applied to enable the decision-maker to select suitable schemes while considering stochastic medical service demand. Moreover, real data cannot been obtained. Hence, according to actual conditions, we assume relative information. For illustrative purposes, a numerical example is presented to verify the effectiveness of the proposed model from experimental data. | [
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The approval of biosimilars requires demonstration of biosimilarity, which rests on the base of thorough analytical characterization of the biosimilar product. In addition to demonstration of biosimilarity, the product related impurities need to be thoroughly characterized and controlled at minimal levels. Pegylation of peptides and proteins creates significant challenges for detailed structural characterization, such as PEG (Poly Ethylene Glycol) heterogeneity, site of addition and number of attached pegylated moieties. A combination of several methods including circular dichroism, FTIR (Fourier-transform Infrared Spectroscopy), fluorescence spectroscopy, DSC (Differential Scanning Calorimetry), 1D and 2D NMR (Nuclear Magnetic Resonance), Edman degradation and peptide mapping by LC-MS (Liquid Chromatography Mass Spectrometry) were used for characterization of N-terminally pegylated filgrastim. Product related impurities such as oxidized, reduced, deamidated, dipegylated variants and monopegylated positional isomers have been characterized in detail using various HPLC (High Performance Liquid Chromatography) based methods and LC-MS techniques. The functional characterization in terms of receptor binding and cell proliferation assay was conducted for the similarity assessment and the potential impact of the product variants on the in vitro biological activity has also been assessed. In summary, this study presents, for the first time, a detailed structural and molecular level characterization of a biosimilar pegfilgrastim providing a strong base for the demonstration of overall biosimilarity of the product with the innovator product. | [
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] |
The clustering of data into physically meaningful subsets often requires assumptions regarding the number, size, or shape of the subgroups. Here, we present a new method, simultaneous coherent structure coloring (sCSC), which accomplishes the task of unsupervised clustering without a priori guidance regarding the underlying structure of the data. sCSC performs a sequence of binary splittings on the dataset such that the most dissimilar data points are required to be in separate clusters. To achieve this, we obtain a set of orthogonal coordinates along which dissimilarity in the dataset is maximized from a generalized eigenvalue problem based on the pairwise dissimilarity between the data points to be clustered. This sequence of bifurcations produces a binary tree representation of the system, from which the number of clusters in the data and their interrelationships naturally emerge. To illustrate the effectiveness of the method in the absence of a priori assumptions, we apply it to three exemplary problems in fluid dynamics. Then, we illustrate its capacity for interpretability using a high-dimensional protein folding simulation dataset. While we restrict our examples to dynamical physical systems in this work, we anticipate straightforward translation to other fields where existing analysis tools require ad hoc assumptions on the data structure, lack the interpretability of the present method, or in which the underlying processes are less accessible, such as genomics and neuroscience. | [
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Interpreting variable laboratory measurements of Helicoverpa zea Boddie susceptibility to toxins from Bacillus thuringiensis Berliner (Bt) has been challenging due to a lack of clear evidence to document declining field control. Research that links laboratory measurements of susceptibility to survival on Bt crops is vital for accurate characterization and any subsequent response to the occurrence of an implied H. zea resistance event. In this study, H. zea survival and the resultant damage to plant fruiting structures of non-Bt, Bollgard II, and Bollgard III cottons from two insect colonies with differing levels of laboratory susceptibility to Bt toxins were evaluated in large field cages. Laboratory bioassays revealed resistance ratios of 2.04 and 622.14 between the two H. zea colonies for Dipel DF and Cry1Ac, respectively. Differences between the two H. zea colonies measured via bioassays with Bollgard II and Bollgard III cotton leaf tissue in the laboratory were not statistically discernable. However, there was 17.6% and 5.3% lower larval mortality in Bollgard II and Bollgard III for the feral relative to the laboratory colony of H. zea, respectively. Although H. zea larval numbers in cages infested with the laboratory susceptible colony did not differ between the two Bt cottons, there were fewer larvae per 25 plants in Bollgard III than in Bollgard II cotton in cages containing tolerant insects. Cages infested with tolerant H. zea moths had higher numbers of total larvae than those containing the laboratory susceptible colony in both Bollgard II and Bollgard III cottons. Bollgard II and Bollgard III cottons received 77.4% and 82.7% more total damage to total plant fruiting structures in cages infested with tolerant insects relative to those containing the laboratory susceptible colony. The damage inflicted to fruiting structures on Bollgard III cotton by a feral H. zea colony with decreased measurements of laboratory susceptibility to Dipel DF and Cry1Ac indicate that the addition of Vip3A to third generation Bt cottons may not provide sufficient control in situations where infestations levels are high. | [
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BACKGROUND: Despite high antiretroviral (ARV) treatment coverage among pregnant women for prevention of mother-to-child transmission (PMTCT) of Human Immunodeficiency Virus (HIV) in Zimbabwe, the MTCT rate is still high. Therefore in 2016, the country adopted World Health Organization recommendations of stratifying pregnant women into "High" or"Low" MTCT risk for subsequent provision of HIV exposed infant (HEI) with appropriate follow-up care according to risk status.OBJECTIVE: The study sought to ascertain, among pregnant women who delivered in clinics of Harare in August 2017: the extent to which high risk MTCT pregnancies were identified at time of delivery; and whether their newborns were initiated on appropriate ARV prophylaxis, cotrimoxazole prophylaxis, subjected to early HIV diagnostic testing and initiated on ARV treatment.METHODS: Cross-sectional study using review of records of routinely collected program data.RESULTS: Of the 1,786 pregnant women who delivered in the selected clinics, HIV status at the time of delivery was known for 1,756 (98%) of whom 197 (11%) were HIV seropositive. Only 19 (10%) could be classified as "high risk" for MTCT and the remaining 90% lacked adequate information to classify them into high or low risk for MTCT due to missing data. Of the 197 live births, only two (1%) infants had a nucleic-acid test (NAT) at birth and 32 (16%) infants had NAT at 6 weeks. Of all 197 infants, 183 (93%) were initiated on single ARV prophylaxis (Nevirapine), 15 (7%) infants' ARV prophylaxis status was not documented and one infant got dual ARV prophylaxis (Nevirapine+Zidovudine).CONCLUSION: There was paucity of data requisite for MTCT risk stratification due to poor recording of data; "high risk" women were missed in the few circumstances where sufficient data were available. Thus "high risk" HEI are deprived of dual ARV prophylaxis and priority HIV NAT at birth and onwards which they require for PMTCT. Health workers need urgent training, mentorship and supportive supervision to master data management and perform MTCT risk stratification satisfactorily. | [
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As result of the great east Japan earthquake on March 2011 and the damages of the Fukushima Dai-ichi Nuclear Power Plant (FDNPP), huge amount of radionuclides, especially 137Cs, were released to the Japanese Pacific coast. By consequence, several marine species have been contaminated by direct uptake of radionuclides from seawater or through feeding on contaminated preys. In the present study we propose a novel radioecological modelling approach aiming to simulate the radionuclides transfer to pelagic marine species by giving to the organism body-size a key role in the model. We applied the model to estimate the 137Cs content in 14 commercially important species of the North-Western Pacific Ocean after the FDNPP accident. Firstly, we validated the model and evaluated its performance using various observed field data, and we demonstrated the importance of using such modelling approach in radioecological studies. Afterwards, we estimated some radioecological metrics, such as the maximum activity concentration, its corresponding time and the ecological half-life, which are important in assessment of the previous, current and future contamination levels of the studied species. Finally, we estimated the time duration required for each species to reach the pre-accident 137Cs activity concentrations. The results showed that the contamination levels in the planktivorous species have generally reached the pre-accident levels since about 5 years after the accident (since 2016). While in the case of the higher trophic level species, although the activity concentrations are much lower than the regulatory limit for radiocesium in seafood in Japan (100 Bq kg-1), these species still require another 6-14 years (2018-2026) to reach the pre-accident levels. | [
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While there is a burgeoning interest in the effects of nutrition on systemic inflammatory diseases, how dietary macronutrient balance impacts local chronic inflammatory diseases in the mouth has been largely overlooked. Here, we used the Geometric Framework for Nutrition to test how the amounts of dietary macronutrients and their interactions, as well as carbohydrate type (starch vs sucrose vs resistant starch) influenced periodontitis-associated alveolar bone height in mice. Increasing intake of carbohydrates reduced alveolar bone height, while dietary protein had no effect. Whether carbohydrate came from sugar or starch did not influence the extent of alveolar bone height. In summary, the amount of carbohydrate in the diet modulated periodontitis-associated alveolar bone height independent of the source of carbohydrates. | [
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River restoration projects focused on altering flow regimes through use of in-channel structures can facilitate ecosystem services, such as promoting nitrogen (N) storage to reduce eutrophication. In this study we use small flux chambers to examine ammonium (NH4+) and nitrate (NO3-) cycling across the sediment-water interface. Paired restored and unrestored study sites in 5 urban tributaries of the River Thames in Greater London were used to examine N dynamics following physical disturbances (0-3 min exposures) and subsequent biogeochemical activity (3-10 min exposures). Average ambient NH4+ concentrations were significantly different amongst all sites and ranged from 28.0 to 731.7 g L-1, with the highest concentrations measured at restored sites. Average NO3- concentrations ranged from 9.6 to 26.4 mg L-1, but did not significantly differ between restored and unrestored sites. Average NH4+ fluxes at restored sites ranged from -8.9 to 5.0 g N m-2 sec-1, however restoration did not significantly influence NH4+ uptake or regeneration (i.e., a measure of release to surface water) between 0-3 minutes and 3-10 minutes. Further, average NO3- fluxes amongst sites responded significantly between 0-3 minutes ranging from -33.6 to 97.7 g N m-2 sec-1. Neither NH4+ nor NO3- fluxes correlated to sediment chlorophyll-a, total organic matter, or grain size. We attributed variations in overall N fluxes to N-specific sediment storage capacity, biogeochemical transformations, potential legacy effects associated with urban pollution, and variations in river-specific restoration actions. | [
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Systematic monitoring of pasture quantity and quality is important to match the herd forage demand (pasture removal by grazing or harvest) to the supply of forage with adequate nutritive value. The aim of this research was to monitor, assess and manage changes in pasture growth, morphology and digestibility by integrating information from an Unmanned Aerial Vehicle (UAV) and two process-based models. The first model, Systems Approach to Land Use Sustainability (SALUS), is a process-based crop growth model used to predict pasture regrowth based on soil, climate, and management data. The second model, Morphogenetic and Digestibility of Pasture (MDP), uses paddock-scale values of herbage mass as input to predict leaf morphogenesis and forage nutritive value. Two field experiments were carried out on tall fescue- and ryegrass-based pastures under rotational grazing with lactating dairy cattle. The first experiment was conducted at plot scale and was used to calibrate the UAV and to test models. The second experiment was conducted at field scale and was used to test the UAV's ability to predict pasture biomass under grazing rotation. The Normalized Difference Vegetation Index (NDVI) calculated from the UAV's multispectral reflectance (n = 72) was strongly correlated (p < 0.001) to plot measurements of pasture biomass (R2 = 0.80) within the range of ~226 and 4208 kg DM ha-1. Moreover, there was no difference (root mean square error, RMSE < 500 kg DM ha-1) between biomass estimations by the UAV (1971350 kg ha-1) and two conventional methods used as control, the C-Dax proximal sensor (2073636 kg ha-1) and ruler (2017530 kg ha-1). The UAV approach was capable of mapping at high resolution (6 cm) the spatial variability of pasture (16 ha). The integrated UAV-modeling approach properly predicted spatial and temporal changes in pasture biomass (RMSE = 509 kg DM ha-1, CCC = 0.94), leaf length (RMSE = 6.2 cm, CCC = 0.62), leaf stage (RMSE = 0.7 leaves, CCC = 0.65), neutral detergent fiber (RMSE = 3%, CCC = 0.71), digestibility of neutral detergent fiber (RMSE = 8%, CCC = 0.92) and digestibility of dry matter (RMSE = 5%, CCC = 0.93) with reasonable precision and accuracy. These findings therefore suggest potential for the present UAV-modeling approach for use as decision support tool to allocate animals based on spatially and temporally explicit predictions of pasture biomass and nutritive value. | [
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IMPORTANCE: Higher levels of red cell distribution width (RDW) are associated with adverse outcomes, especially in selected cohorts with or at risk for chronic disease. Whether higher RDW or the related parameter standard deviation of the red blood cell distribution (SD-RBC) can predict a broader range of outcomes in the general population is unknown.OBJECTIVE: To evaluate the association of RDW and SD-RBC with the risk of adverse outcomes in people from the general population.DESIGN: Population-based retrospective cohort study.SETTING: Health care system in a Canadian province (Alberta).PARTICIPANTS: All 3,156,863 adults living in Alberta, Canada with at least one measure of RDW and SD-RBC between 2003 and 2016. Data were analyzed in September 2018.EXPOSURE: RDW and SD-RBC, classified into percentiles (<1, 1-5, 5-25, 25-75, 75-95, 95-99, >99).MAIN OUTCOMES: All-cause death, first myocardial infarction, first stroke or transient ischemic attack, placement into long-term care (LTC), progression to renal replacement therapy (initiation of chronic dialysis or pre-emptive kidney transplantation), incident solid malignancy, and first hospitalization during follow-up.RESULTS: Over median follow-up of 6.8 years, 209,991 of 3,156,863 participants (6.7%) died. The risk of death increased with increasing RDW percentile. After adjustment, and compared to RDW in the 25th to 75th percentiles, the risk of death was lower for participants in the <25th percentiles but higher for participants in the 75th-95th percentiles (HR 1.42, 95% CI 1.40,1.43), the 95th-99th percentiles (HR 1.86, 95% CI 1.83,1.89) and the >99th percentile (HR 2.18, 95% CI 2.12,2.23). Similar results were observed for MI, stroke/TIA, incident cancer, hospitalization and LTC placement, but no association was found between RDW and ESRD. Findings were generally similar for SD-RBC, except that all associations tended to be stronger than for RDW, and both lower and higher values of SD-RBC were independently associated with ESRD.CONCLUSION AND RELEVANCE: RDW and SD-RBC may be useful as prognostic markers for people in the general population, especially for outcomes related to chronic illness. SD-RBC may be superior to RDW. | [
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The fundamental test for male infertility, semen analysis, is mostly a manually performed subjective and time-consuming process and the use of automated systems has been cost prohibitive. We have previously developed an inexpensive smartphone-based system for at-home male infertility screening through automatic and rapid measurement of sperm concentration and motility. Here, we assessed the feasibility of using a similar smartphone-based system for laboratory use in measuring: a) Hyaluronan Binding Assay (HBA) score, a quantitative score describing the sperm maturity and fertilization potential in a semen sample, b) sperm viability, which assesses sperm membrane integrity, and c) sperm DNA fragmentation that assesses the degree of DNA damage. There was good correlation between the manual analysis and smartphone-based analysis for the HBA score when the device was tested with 31 fresh, unprocessed human semen samples. The smartphone-based approach performed with an accuracy of 87% in sperm classification when the HBA score was set at manufacturer's threshold of 80. Similarly, the sperm viability and DNA fragmentation tests were also shown to be compatible with the smartphone-based system when tested with 102 and 47 human semen samples, respectively. | [
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Regenerative medicine has received a lot of attention as a novel strategy for injuries and diseases that are difficult to cure using current techniques. Cell production, which is vital for regenerative medicine, has undergone remarkable progress via breakthroughs in developmental biology and tissue engineering; currently, cell production requires numerous experimental operators performing manual, small-scale cell cultures. Other major obstacles for cell production and regenerative medicine include the variable quality of products based on the experimental procedure, the skills of operators, the level of labor required for production, and costs. Technological developments are required to overcome this, including automation instead of manual culture. Age-related macular regeneration (AMD) is a refractory ocular disease that causes severe deterioration in central vision due to senescence in the retinal pigment epithelium (RPE). Recently, we performed an autologous transplantation of induced pluripotent stem (iPS) cell-derived RPE cell sheets and started clinical research on allografts from RPE cell suspensions differentiated from iPS cells. The use of regenerative therapies for AMD using iPS cell-derived RPE is expected to become more widespread. In the present study, human iPS cell-derived RPE cells were cultured to form RPE cell sheets using equipment with a closed culture module. The quality of the automated cultured RPE cell sheets was confirmed by comparing their morphological and biological properties with those of manually generated RPE cell sheets. As a result, machine-cultured RPE sheets displayed the same quality as manually cultured RPE sheets, showing that iPS cell-derived RPE cell sheets were successfully cultured by an automated process. | [
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This study examines the prevalence and correlates of stroke among older adults in Ghana. This cross-sectional study retrieved data from Wave 1 of the World Health Organization (WHO) Survey on Global Ageing and Adult Health (SAGE) conducted between 2007 and 2008. The sample, comprising 4,279 respondents aged 50 years and above, was analysed using descriptive statistics, cross tabulations and Chi-Square tests, and a multivariable binary logistic regression. Respondents ranged in age from 50 to 114 years, with a median age of 62 years. Stroke prevalence was 2.6%, with the correlates being marital status, level of education, employment status, and living with hypertension or diabetes. The results showed that being separated/divorced, having primary and secondary education, being unemployed and living with hypertension and diabetes, significantly increased the odds of stroke prevalence in this population. The results suggest that interventions to reduce stroke prevalence and impact must be developed alongside interventions for hypertension, diabetes and sociodemographic/economic factors such as marital status, level of education, and employment status. | [
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The wording negotiators use shapes the emotions of their counterparts. These emotions, in turn, influence their counterparts' economic decisions. Building on this rationale, we examined how the language used during negotiation affects discount rate and willingness to engage in future deals. In three studies, participants assumed the role of retailers. Alleged counterparts (actually a computerized program) asked for a discount under three conditions: request, want, and demand. Results show that less extreme language (request/want) resulted in better outcomes than demanding a discount. Moreover, while the language used by the customer had an effect on experienced emotions, the positive emotions (sympathy and empathy) participants felt toward the customer mediated the relationship between the linguistic cue and the negotiation outcome. Our results inform both psycholinguistic research and negotiation research by demonstrating the causal role of linguistic cues in activating concept-knowledge relevant to different emotional experiences, and point to the down-the-line impact on shaping negotiation preferences. | [
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BACKGROUND: Psychological distress including depression and anxiety are among the most serious causes of morbidity and mortality in Bangladesh. There has been no study in the rural area to report the prevalence of and risk factors for psychological distress. The aim of this study was to estimate the prevalence of and risk factors for psychological distress in a rural district in Bangladesh.METHODS: A total of 2425 adults (1249 women) aged 18-90 years were selected from the Narail upazilla using multi-level cluster random sampling for a cross-sectional study. Psychological distress was assessed using the Kessler 10 items questionnaire. Participants' socio-demographic status, life style factors and health conditions were also collected. Odds ratios and 95% confidence intervals for binary outcomes and mean changes for continuous outcomes of psychological distress score were computed. Logistic regression and generalized linear model techniques were used for analytical purpose.RESULTS: The overall prevalence of psychological distress was 52.5%. This proportion included 22.7% people rated as having mild psychological distress, 20.8% moderate and 9.0% severe. The prevalence of moderate (24.7% vs. 17.5%, p<0.001) and severe (16.2% vs. 2.5%, p<0.001) psychological distress was significantly higher in older adults of age 60-90 years than that in younger adults of age 18-59 years. The prevalence of severe psychological distress was higher in females than males and the difference increased with age (vs. (females vs males: 1.9% vs. 1.1% at age of <30 years, 12.2% vs. 10.1% at age between 60-69 years, and 45.5% vs. 25.4% at age of 80 years or older). After multivariate adjustment, compared to degree or equivalent level of education, no education (odds ratio (OR), 1.71, 95% confidence interval (CI), 1.03-2.82) was associated with higher prevalence of any psychological distress in the total sample. Compared to married, psychological distress among widowed older adults was almost five times higher prevalence (OR, 4.89, 95% CI, 2.51-9.55). Socio-economic status showed a U-shaped relationship with the prevalence of psychological distress; being very poor or wealthy was associated with higher prevalence of psychological distress compared to those of moderate socio-economic status. People living in pourashava (semi-urban areas) reported significantly higher prevalence of psychological distress compared to people living in typical rural unions.CONCLUSIONS: In this rural Bangladeshi community, the prevalence of psychological distress was high, especially among older women. Factors including lower level of education, inability to work, and living in semi-urban areas were associated with higher prevalence of psychological distress. Public health programmes should target people in high risk groups to reduce their psychological distress in Bangladesh. | [
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Human presence at intertidal areas could impact coastal biodiversity, including migratory waterbird species and the ecosystem services they provide. Assessing this impact is therefore essential to develop management measures compatible with migratory processes and associated biodiversity. Here, we assess the effects of human presence on the foraging opportunities of Hudsonian godwits (Limosa haemastica, a trans-hemispheric migratory shorebird) during their non-breeding season on Chilo? Island, southern Chile. We compared bird density and time spent foraging in two similar bays with contrasting disturbance levels: human presence (mostly seaweed harvesters accompanied by dogs) was on average 0.90.4 people per 10 ha in the disturbed bay, whereas it was negligible (95% days absent) in the non-disturbed bay. Although overall abundances were similar between bays, godwit density was higher in the non-disturbed bay throughout the low tide period. Both days after the start of the non-breeding season and tidal height significantly affected godwit density, with different effects in either bay. Time spent foraging was significantly higher in the non-disturbed bay (86.51.1%) than in the disturbed one (81.31.4%). As expected, godwit density significantly decreased with the number of people and accompanying dogs in the disturbed bay. Our results indicate that even a low density of people and dogs can significantly reduce the foraging opportunities of shorebirds. These constraints, coupled with additional flushing costs, may negatively affect godwits' pre-migratory fattening. Hence, as a first step we suggest limiting human presence within bays on Chilo? to 1 person per 10 ha and banning the presence of accompanying dogs in sensitive conservation areas. | [
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BACKGROUND: Enhancing evidence-based practice and improving locally driven research begins with fostering the research skills of undergraduate students in the medical and health sciences. Research as a core component of undergraduate curricula can be facilitated or constrained by various programmatic and institutional factors, including that of choice. Self-Determination Theory (SDT) provides a framework for understanding the influence of choice on student motivation to engage in research.AIM: This study aimed to document the enablers and constraints of undergraduate research at a South African Faculty of Medicine and Health Sciences (FMHS) and to explore how the presence or absence of choice influenced students' engagement with research in this context.METHODS: An exploratory descriptive design was adopted. Undergraduate students who had conducted research and undergraduate programme staff were recruited through purposive sampling. Semi-structured interviews were transcribed and thematically analysed. Findings were interpreted using SDT, focusing on how choice at various levels affects motivation and influences research experiences.RESULTS: Many of the programmatic and institutional enablers and constraints-such as time and supervisory availability-were consistent with those previously identified in the literature, regardless of whether research was compulsory or elective. Choice itself seemed to operate as both an enabler and a constraint, highlighting the complexity of choice as an influence on student motivation. SDT provided insight into how programmatic and institutional factors-and in particular choice-supported or suppressed students' needs for autonomy, competence, and relatedness, thereby influencing their motivation to engage in research.CONCLUSION: While programmatic and institutional factors may enable or constrain undergraduate research, individual-level factors such as the influence of choice on students' motivation play a critical role. The implication for curriculum development is that research engagement might be enhanced if levels of choice are structured into the curriculum such that students' needs for autonomy, competence, and relatedness are met. | [
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Baphicacanthus cusia (Nees) Bremek (B. cusia) is an effective herb for the treatment of acute promyelocytic leukemia and psoriasis in traditional Chinese medicine. Methyl jasmonate (MeJA) is a well-known signaling phytohormone that triggers gene expression in secondary metabolism. Currently, MeJA-mediated biosynthesis of indigo and indirubin in B. cusia is not well understood. In this study, we analyzed the content of indigo and indirubin in leaf and root tissues of B. cusia with high-performance liquid chromatography and measured photosynthetic characteristics of leaves treated by MeJA using FluorCam6 Fluorometer and chlorophyll fluorescence using the portable photosynthesis system CIRAS-2. We performed de novo RNA-seq of B. cusia leaf and root transcriptional profiles to investigate differentially expressed genes (DEGs) in response to exogenous MeJA application. The amount of indigo in MeJA-treated leaves were higher than that in controled leaves (p = 0.004), and the amounts of indigo in treated roots was higher than that in controlled roots (p = 0.048); Chlorophyll fluorescence of leaves treated with MeJA were significantly decreased. Leaves treated with MeJA showed lower photosynthetic rate compared to the control in the absence of MeJA. Functional annotation of DEGs showed the DEGs related to growth and development processes were down-regulated in the treated leaves, while most of the unigenes involved in the defense response were up-regulated in treated roots. This coincided with the effects of MeJA on photosynthetic characteristics and chlorophyll fluorescence. The qRT-PCR results showed that MeJA appears to down-regulate the gene expression of tryptophan synthase -subunits (trpA-) in leaves but increased the gene expression of anthranilate synthase (trp 3) in roots responsible for increased indigo content. The results showed that MeJA suppressed leaf photosynthesis for B. cusia and this growth-defense trade-off may contribute to the improved adaptability of B. cusia in changing environments. | [
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Mexican tropical dry forests are remarkably extensive and floristically diverse despite manifesting alarming rates of deforestation. Riparian habitats within dry forests provide critical ecological benefits that may mitigate negative impacts, but processes underlying riparian functions are still not well understood. We identified physical environmental conditions affecting the composition and abundance of standing vegetation assemblages and woody and herbaceous components in soil seedbank assemblages of riparian corridors in central Mexico using mainly NMDS ordination techniques, permuted analysis of variance (PERMANOVA), permuted analysis of multivariate dispersions and constrained ordination (CAP). We then determined representative species associated with particular environmental conditions using an indicator species analysis and assessed the effects of physical environmental variables/factors on total seed abundances by fitting a mixed-effect model. For the standing vegetation study, we assessed the effects of the type of the river condition (differing in surface flow permanence), location, and height above river level on the community composition based on three species importance criteria (abundance, coverage and DBH). For the soil seedbank study, we assessed the effects of these variables/factors plus season and land use. Spatial heterogeneity was a prevailing feature in riparian vegetation, in the standing vegetation and soil seedbank of both woody and herbaceous components. Height above river level had a significant effect on the three species importance criteria of standing vegetation and so did the interaction between surface flow permanence and height on coverage. The soil seedbank of woody and herbaceous plants showed significant differences between seasons; Taxodium mucronatum was an indicator tree species in dry seasons. Land use, height, surface flow permanence and the interaction between land use and surface flow permanence had significant effects on the soil seedbank of herbaceous plants. Total seed abundances in the soil varied between years and were higher at lower height values, during the dry seasons, and when rivers were permanent. Tree communities, commonly the most important elements in riparian ecosystems, were preserved in the soil seedbank of cultivated areas for >30 years. Seeds of herbaceous communities were predominant and ecologically relevant as indicator species because of their high sensitivity to several key environmental factors, constituting a critical component of Mexican tropical dry forests riparian corridors. | [
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After being the standard plant propagation protocol for decades, cultures of Arabidopsis thaliana sealed with Parafilm remain common today out of practicality, habit, or necessity (as in co-cultures with microorganisms). Regardless of concerns over the aeration of these cultures, no investigation has explored the CO2 transport inside these cultures and its effect on the plants. Thereby, it was impossible to assess whether Parafilm-seals used today or in thousands of older papers in the literature constitute a treatment, and whether this treatment could potentially affect the study of other treatments.For the first time we report the CO2 concentrations in Parafilm-sealed cultures of A. thaliana with a 1 minute temporal resolution, and the transcriptome comparison with aerated cultures. The data show significant CO2 deprivation to the plants, a drastic suppression of photosynthesis, respiration, starch accumulation, chlorophyll biosynthesis, and an increased accumulation of reactive oxygen species. Most importantly, CO2 deprivation occurs as soon as the cotyledons emerge. Gene expression analysis indicates a significant alteration of 35% of the pathways when compared to aerated cultures, especially in stress response and secondary metabolism processes. On the other hand, the observed increase in the production of glucosinolates and flavonoids suggests intriguing possibilities for CO2 deprivation as an organic biofortification treatment in high-value crops. | [
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BACKGROUND: Acute kidney injury (AKI) is a common complication of extracorporeal membrane oxygenation (ECMO) treatment. The aim of this study was to elucidate the long-term outcomes of adult patients with AKI who receive ECMO.MATERIALS AND METHODS: The study analyzed encrypted datasets from Taiwan's National Health Insurance Research Database. The data of 3251 patients who received first-time ECMO treatment between January 1, 2003, and December 31, 2013, were analyzed. Characteristics and outcomes were compared between patients who required dialysis for AKI (D-AKI) and those who did not in order to evaluate the impact of D-AKI on long-term mortality and major adverse kidney events.RESULTS: Of the 3251 patients, 54.1% had D-AKI. Compared with the patients without D-AKI, those with D-AKI had higher rates of all-cause mortality (52.3% vs. 33.3%; adjusted hazard ratio [aHR] 1.82, 95% confidence interval [CI] 1.53-2.17), chronic kidney disease (13.7% vs. 8.1%; adjusted subdistribution HR [aSHR] 1.66, 95% CI 1.16-2.38), and end-stage renal disease (5.2% vs. 0.5%; aSHR 14.28, 95% CI 4.67-43.62). The long-term mortality of patients who survived more than 90 days after discharge was 22.0% (153/695), 32.3% (91/282), and 50.0% (10/20) in the patients without D-AKI, with recovery D-AKI, and with nonrecovery D-AKI who required long-term dialysis, respectively, demonstrating a significant trend (Pfor trend <0.001).CONCLUSION: AKI is associated with an increased risk of long-term mortality and major adverse kidney events in adult patients who receive ECMO. | [
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How do large-mammal communities reassemble after being pushed to the brink of extinction? Few data are available to answer this question, as it is rarely possible to document both the decline and recovery of wildlife populations. Here we present the first in-depth quantitative account of war-induced collapse and postwar recovery in a diverse assemblage of large herbivores. In Mozambique's Gorongosa National Park, we assembled data from 15 aerial wildlife counts conducted before (1968-1972) and after (1994-2018) the Mozambican Civil War (1977-1992). Pre-war total biomass density exceeded 9,000 kg km-2, but populations declined by >90% during the war. Since 1994, total biomass has substantially recovered, but species composition has shifted dramatically. Formerly dominant large herbivores-including elephant (Loxodonta africana), hippo (Hippopotamus amphibius), buffalo (Syncerus caffer), zebra (Equus quagga), and wildebeest (Connochaetes taurinus)-are now outnumbered by waterbuck (Kobus ellipsiprymnus) and other small to mid-sized antelopes. Waterbuck abundance has increased by an order of magnitude, with >55,000 individuals accounting for >74% of large-herbivore biomass in 2018. By contrast, elephant, hippo, and buffalo, which totaled 89% of pre-war biomass, now comprise just 23%. These trends mostly reflect natural population growth following the resumption of protection under the Gorongosa Restoration Project; reintroductions (465 animals of 7 species) accounted for a comparatively small fraction of the total numerical increase. Waterbuck are growing logistically, apparently as-yet unchecked by interspecific competition or predation (apex-carnivore abundance has been low throughout the post-war interval), suggesting a community still in flux. Most other herbivore populations have increased post-war, albeit at differing rates. Armed conflict remains a poorly understood driver of ecological change; our results demonstrate the potential for rapid post-war recovery of large-herbivore biomass, given sound protected-area management, but also suggest that restoration of community structure takes longer and may require active intervention. | [
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BACKGROUND: The highest burden of disease from hepatitis C virus (HCV) is found in Southeast Asia, but our understanding of the epidemiology of infection in many heavily burdened countries is still limited. In particular, there is relatively little data on acute HCV infection, the outcome of which can be influenced by both viral and host genetics which differ within the region. We studied HCV genotype and IL28B gene polymorphism in a cohort of acute HCV-infected patients in Southern Vietnam alongside two other cohorts of chronic HCV-infected patients to better understand the epidemiology of HCV infection locally and inform the development of programs for therapy with the increasing availability of directly acting antiviral therapy (DAAs).METHODS: We analysed plasma samples from patients with acute and chronic HCV infection, including chronic HCV mono-infection and chronic Human Immunodeficiency Virus (HIV)-HCV coinfection, who enrolled in four epidemiological or clinical research studies. HCV infection was confirmed with RNA testing. The 5' UTR, core and NSB5 regions of HCV RNA positive samples were sequenced, and the genotype and subtype of the viral strains were determined. Host DNA from all HCV positive patients and age- and sex-matched non-HCV-infected control individuals were analysed for IL28B single nucleotide polymorphism (SNP) (rs12979860 and rs8099917). Geolocation of the patients were mapped using QGIS.RESULTS: 355 HCV antibody positive patients were analysed; 54.6% (194/355) and 46.4% (161/355) were acute and chronic infections, respectively. 50.4% (81/161) and 49.6.4% (80/161) of chronic infections had HCV mono-infection and HIV-HCV coinfection, respectively. 88.7% (315/355) and 10.1% (36/355) of the patients were from southern and central regions of Vietnam, respectively. 92.4% (328/355) of patients were HCV RNA positive, including 86.1% (167/194) acute and 100% (161/161) chronic infections. Genotype could be determined in 98.4% (322/328) patients. Genotypes 1 (56.5%; 182/322) and 6 (33.9%; 109/322) predominated. Genotype 1 including genotype 1a was significantly higher in HIV-HCV coinfected patients compared to acute HCV patients [43.8% (35/80) versus 20.5% (33/167)], (p = <0.001), while genotype 6 was significantly higher in chronic HCV mono-infected patients [(44.4% (36/81) versus 20.0% (16/80)] (p = < 0.004) compared to HIV-HCV coinfected patients. The prevalence of IL28B SNP (rs12979860) homozygous CC was 86.46% (83/96) in control individuals and was significantly higher in acutely-infected compared to chronically-infected patients [93.2 (82/88) versus 76.1% (35/46)] (p = < 0.005).CONCLUSION: HCV genotype 6 is highly prevalent in Vietnam and the high prevalence in treatment na?ve chronic HCV patients may results from poor spontaneous clearance of acute HCV infection with genotype 6. | [
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Eukaryotic DNA binding proteins must access genomic DNA that is packaged into chromatin in vivo. During a productive infection, retroviral integrases (IN) must similarly interact with chromatin to integrate the viral cDNA genome. Here we examine the role of nucleosome DNA unwrapping in the retroviral integrase search for a target site. These studies utilized PFV intasomes that are comprised of a tetramer of PFV IN with two oligomers mimicking the viral cDNA ends. Modified recombinant human histones were used to generate nucleosomes with increased unwrapping rates at different DNA regions. These modifications included the acetylmimetic H3(K56Q) and the chemically engineered H4(K77ac, K79ac). While transcription factors and DNA damage sensors may search nucleosome bound DNA during transient unwrapping, PFV intasome mediated integration appears to be unaffected by increased nucleosome unwrapping. These studies suggest PFV intasomes do not utilize nucleosome unwrapping to search nucleosome targets. | [
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] |
Due to low labeling efficiency and structural heterogeneity in fluorescence-based single-molecule localization microscopy (SMLM), image alignment and quantitative analysis is often required to make accurate conclusions on the spatial relationships between proteins. Cryo-electron microscopy (EM) image alignment procedures have been applied to average structures taken with super-resolution microscopy. However, unlike cryo-EM, the much larger cellular structures analyzed by super-resolution microscopy are often heterogeneous, resulting in misalignment. And the light-microscopy image library is much smaller, which makes classification challenging. To overcome these two challenges, we developed a method to deform semi-flexible ring-shaped structures and then align the 3D structures without classification. These algorithms can register semi-flexible structures with an accuracy of several nanometers in short computation time and with greatly reduced memory requirements. We demonstrated our methods by aligning experimental Stochastic Optical Reconstruction Microscopy (STORM) images of ciliary distal appendages and simulated structures. Symmetries, dimensions, and locations of protein complexes in 3D are revealed by the alignment and averaging for heterogeneous, tilted, and under-labeled structures. | [
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Shark meat is consumed as a food source worldwide, especially in Asian countries. However, since sharks are apex predators in the ocean food chain, they are prone to bioaccumulation of heavy metals. More than 100 million sharks are caught annually for human consumption, and the safety of shark meat cannot be overemphasized. Here, we examined heavy metal concentration in the muscle tissue of 6 shark species including 3 migratory species (Carcharhinus brachyurus, Carcharhinus obscurus, and Isurus oxyrinchus) and 3 local species (Triakis scyllium, Mustelus manazo, and Cephaloscyllium umbratile) from fish markets in Jeju Island, Republic of Korea. The concentrations of 11 heavy metals (Cr, Fe, Cu, Zn, As, Se, Cd, Sn, Sb, Pb, and Hg) and MeHg were analyzed. The result showed that the average concentrations of all metals, except for that of As, were below the regulatory maximum limits of many organizations, including the Codex standard. Hg and MeHg were significantly correlated with body length, body weight, and age, and the concentration of Hg was expected to exceed the limit in C. brachyurus with a body length or weight of over 130 cm or 25 kg, respectively. Our results indicate that shark meat can expose consumers to a high level of As and that copper sharks bigger than the predicted size should be avoided for excessive Hg. Considering these findings, a detailed guideline on consumption of meat of different shark species should be suggested based on further investigation. | [
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Research into sports team performance has shown that across many sports and league competitions, teams that change their coaches after a decline in performance do rebound, but fare no better on average than teams that have not changed their coach in a similar situation. A similar lack of succession benefits has been reported in studies of manager and CEO succession: it has not been established that changing a team's leader improves a declining team's performance. We study the effect of a change of coach on the performance of a professional soccer team. Based on rarely obtained access to a whole season (one year) of daily close observation of the team and coaching staff in practice and matches, this study uses quantitative and qualitative data to go beyond the "average" pattern reported in the literature. We document in detail how, in a single team case study over an entire season, the processes in leadership behavior changed with a change of coach, the effect this had on the state of mind of the team, how the match behaviors of the players changed, and how these changes translated into improved performance. The process effects of a leadership change on the performance of a sports team may hold insights for leader succession in management: in addition to the aggregate organizational and experience fit of the new team leader, the specific leadership processes introduced by the new leader are critical for performance effects. | [
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Financial time series forecasting is a crucial measure for improving and making more robust financial decisions throughout the world. Noisy data and non-stationarity information are the two key factors in financial time series prediction. This paper proposes twin support vector regression for financial time series prediction to deal with noisy data and nonstationary information. Various interesting financial time series datasets across a wide range of industries, such as information technology, the stock market, the banking sector, and the oil and petroleum sector, are used for numerical experiments. Further, to test the accuracy of the prediction of the time series, the root mean squared error and the standard deviation are computed, which clearly indicate the usefulness and applicability of the proposed method. The twin support vector regression is computationally faster than other standard support vector regression on the given 44 datasets. | [
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BACKGROUND: Invasive meningococcal disease (IMD) is a highly lethal disease. Diagnosis is commonly performed by culture or Realtime-PCR (qPCR).AIMS: Our aim was to evaluate, retrospectively, whether culture positivity correlates with higher bacterial load and fatal outcome. Our secondary aim was to compare culture and qPCR sensitivity.METHODS: The National Register for Molecular Surveillance was used as data source. Cycle threshold (CT), known to be inversely correlated with bacterial load, was used to compare bacterial load in different samples.RESULTS: Three-hundred-thirteen patients were found positive for Neisseria meningitidis by qPCR, or culture, or both; 41 died (case fatality rate 13.1%); 128/143 (89.5%) blood samples and 138/144 (95.8%) CSF were positive by qPCR, 37/143 (25.9%) blood samples and 45/144 (31.2%) CSF were also positive in culture. qPCR was 3.5 times (blood) or 3.1 times (CSF) more sensitive than culture in achieving a laboratory diagnosis of IMD (OR 24.4; 95% CI 12.2-49.8; p < .10-4; Cohen's 0.08 for blood and OR 49.0; 95% CI 19.1-133.4; p<10-4; Cohen's 0.02; for CSF). Positivity of culture did not correlate with higher bacterial loads in blood (mean CT 27.75.71, and CT 28.16.03, p = 0.739 respectively in culture positive or negative samples) or in CSF (mean CT 23.14.9 and 24.75.4 respectively in positive or negative CSF samples, p = 0.11).CT values in blood from patients who died were significantly lower than in patients who survived (respectively mean 18.0, range 14-23 and mean 29.6, range 16-39; p<10-17). No deaths occurred in patients with CT in blood over 23. Positive blood cultures were found in 10/25 (40%) patients who died and in 32/163 (19.6%) patients who survived, p = 0.036, OR 2.73; 95% CL 1.025-7.215), however 60% of deaths would have remained undiagnosed with the use of culture only.CONCLUSIONS: In conclusion our study demonstrated that qPCR is significantly (at least 3 times) more sensitive than culture in the laboratory confirmation of IMD. The study also demonstrated that culture negativity is not associated with lower bacterial loads and with less severe cases. On the other side, in patients with sepsis, qPCR can predict fatal outcome since higher bacterial load, evaluated by qPCR, appears strictly associated with most severe cases and fatal outcome. The study also showed that molecular techniques such as qPCR can provide a valuable addition to the proportion of diagnosed and serotyped cases of IMD. | [
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The obligate mutualism and exquisite specificity of many plant-pollinator interactions lead to the expectation that flower phenotypes (e.g., corolla tube length) and corresponding pollinator traits (e.g., hawkmoth proboscis length) are congruent as a result of coevolution by natural selection. However, the effect of variation in flower morphology on the fitness of plants and their pollinators has not been quantified systematically. In this study, we employed the theoretical morphospace paradigm using a combination of 3D printing, electronic sensing, and machine vision technologies to determine the influence of two flower morphological features (corolla curvature and nectary diameter) on the fitness of both parties: the artificial flower and its hawkmoth pollinator. Contrary to the expectation that the same flower morphology maximizes the fitness of both plant and pollinator, we found that the two parties have divergent optima for corolla curvature, with non-overlapping fitness peaks in flower morphospace. The divergent fitness optima between plants and pollinators could lead to evolutionary diversification in both groups. | [
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Barrett's esophagus (BE) is an abnormality arising from gastroesophageal reflux disease that can progressively evolve into a sequence of dysplasia and adenocarcinoma. Progression of Barrett's esophagus into dysplasia is monitored with endoscopic surveillance. The current surveillance standard requests random biopsies plus targeted biopsies of suspicious lesions under white-light endoscopy, known as the Seattle protocol. Recently, published evidence has shown that narrow-band imaging (NBI) can guide targeted biopsies to identify dysplasia and reduce the need for random biopsies. We aimed to assess the health economic implications of adopting NBI-guided targeted biopsy vs. the Seattle protocol from a National Health Service England perspective. A decision tree model was developed to undertake a cost-consequence analysis. The model estimated total costs (i.e. staff and overheads; histopathology; adverse events; capital equipment) and clinical implications of monitoring a cohort of patients with known/suspected BE, on an annual basis. In the simulation, BE patients (N = 161,657 at Year 1; estimated annual increase: +20%) entered the model every year and underwent esophageal endoscopy. After 7 years, the adoption of NBI with targeted biopsies resulted in cost reduction of 458.0 mln vs. HD-WLE with random biopsies (overall costs: 1,966.2 mln and 2,424.2 mln, respectively). The incremental investment on capital equipment to upgrade hospitals with NBI (+68.3 mln) was offset by savings due to the reduction of histological examinations (-505.2 mln). Reduction of biopsies also determined savings for avoided adverse events (-21.1 mln). In the base-case analysis, the two techniques had the same accuracy (number of correctly identified cases: 1.934 mln), but NBI was safer than HD-WLE. Budget impact analysis and cost-effectiveness analyses confirmed the findings of the cost-consequence analysis. In conclusion, NBI-guided targeted biopsies was a cost-saving strategy for NHS England, compared to current practice for detection of dysplasia in patients with BE, whilst maintaining at least comparable health outcomes for patients. | [
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BACKGROUND: Intelligent decision support systems (IDSS) have been applied to tasks of disease management. Deep neural networks (DNNs) are artificial intelligent techniques to achieve high modeling power. The application of DNNs to large-scale data for estimating stroke risk needs to be assessed and validated. This study aims to apply a DNN for deriving a stroke predictive model using a big electronic health record database.METHODS AND RESULTS: The Taiwan National Health Insurance Research Database was used to conduct a retrospective population-based study. The database was divided into one development dataset for model training (~70% of total patients for training and ~10% for parameter tuning) and two testing datasets (each ~10%). A total of 11,192,916 claim records from 840,487 patients were used. The primary outcome was defined as any ischemic stroke in inpatient records within 3 years after study enrollment. The DNN was evaluated using the area under the receiver operating characteristic curve (AUC or c-statistic). The development dataset included 672,214 patients (a total of 8,952,000 records) of whom 2,060 patients had stroke events. The mean age of the population was 35.520.2 years, with 48.5% men. The model achieved AUC values of 0.920 (95% confidence interval [CI], 0.908-0.932) in testing dataset 1 and 0.925 (95% CI, 0.914-0.937) in testing dataset 2. Under a high sensitivity operating point, the sensitivity and specificity were 92.5% and 79.8% for testing dataset 1; 91.8% and 79.9% for testing dataset 2. Under a high specificity operating point, the sensitivity and specificity were 80.3% and 87.5% for testing dataset 1; 83.7% and 87.5% for testing dataset 2. The DNN model maintained high predictability 5 years after being developed. The model achieved similar performance to other clinical risk assessment scores.CONCLUSIONS: Using a DNN algorithm on this large electronic health record database is capable of obtaining a high performing model for assessment of ischemic stroke risk. Further research is needed to determine whether such a DNN-based IDSS could lead to an improvement in clinical practice. | [
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] |
Based on the Markowitz mean variance model, this paper discusses the portfolio selection problem in an uncertain environment. To construct a more realistic and optimized model, in this paper, a new general interval quadratic programming model for portfolio selection is established by introducing the linear transaction costs and liquidity of the securities market. Regarding the estimation for the new model, we propose an effective numerical solution method based on the Lagrange theorem and duality theory, which can obtain the effective upper and lower bounds of the objective function of the model. In addition, the proposed method is illustrated with two examples, and the results show that the proposed method is better and more feasible than the commonly used portfolio selection method. | [
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] |
The health and function of tissue rely on its vasculature network to provide reliable blood perfusion. Volumetric imaging approaches, such as multiphoton microscopy, are able to generate detailed 3D images of blood vessels that could contribute to our understanding of the role of vascular structure in normal physiology and in disease mechanisms. The segmentation of vessels, a core image analysis problem, is a bottleneck that has prevented the systematic comparison of 3D vascular architecture across experimental populations. We explored the use of convolutional neural networks to segment 3D vessels within volumetric in vivo images acquired by multiphoton microscopy. We evaluated different network architectures and machine learning techniques in the context of this segmentation problem. We show that our optimized convolutional neural network architecture with a customized loss function, which we call DeepVess, yielded a segmentation accuracy that was better than state-of-the-art methods, while also being orders of magnitude faster than the manual annotation. To explore the effects of aging and Alzheimer's disease on capillaries, we applied DeepVess to 3D images of cortical blood vessels in young and old mouse models of Alzheimer's disease and wild type littermates. We found little difference in the distribution of capillary diameter or tortuosity between these groups, but did note a decrease in the number of longer capillary segments (>75m) in aged animals as compared to young, in both wild type and Alzheimer's disease mouse models. | [
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] |
AIMS: Numerous healthcare decisions are faced by persons with advanced cancer from diagnosis to end-of-life. The family caregiver role in these decisions has focused on being a surrogate decision-maker, however, little is known about the caregiver's role in supporting upstream patient decision-making. We aimed to describe the roles of family caregivers in assisting community-dwelling advanced cancer patients with healthcare decision-making across settings and contexts.METHODS: Qualitative study using one-on-one, semi-structured interviews with community-dwelling persons with metastatic cancer (n = 18) and their family caregivers (n = 20) recruited from outpatient oncology clinics of a large tertiary care academic medical center, between October 2016 and October 2017. Transcribed interviews were analyzed using a thematic analysis approach.FINDINGS: Caregivers averaged 56 years and were mostly female (95%), white (85%), and the patient's partner/spouse (70%). Patients averaged 58 years and were mostly male (67%) in self-reported "fair" or "poor" health (50%) with genitourinary (33%), lung (17%), and hematologic (17%) cancers. Themes describing family member roles in supporting patients' upstream healthcare decision-making were: 1) seeking information about the cancer, its trajectory, and treatments options; 2) ensuring family and healthcare clinicians have a common understanding of the patient's treatment plan and condition; 3) facilitating discussions with patients about their values and the framing of their illness; 5) posing "what if" scenarios about current and potential future health states and treatments; 6) addressing collateral decisions (e.g., work arrangements) resulting from medical treatment choices; 6) originating healthcare-related decision points, including decisions about seeking emergency care; and 7) making healthcare decisions for patients who preferred to delegate healthcare decisions to their family caregivers.CONCLUSIONS: These findings highlight a previously unreported and understudied set of critical decision partnering roles that cancer family caregivers play in patient healthcare decision-making. Optimizing these roles may represent novel targets for early decision support interventions for family caregivers. | [
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Diagnostic and Statistical Manual of mental disorder-IV (DSM-IV) TR based INCLEN Diagnostic Tool for Autism Spectrum Disorder (INDT-ASD) is an established instrument for the diagnosis of ASD in Indian subcontinent and low-middle income countries (LMIC). The introduction of DSM-5 necessitated revision of existing INDT-ASD tool to incorporate the DSM-5 related changes. This study was undertaken to develop and validate the DSM-5 based All India Institute of Medical Sciences (AIIMS)-Modified-INDT-ASD Tool. The modifications were done using Delphi method and included: (a) rearrangement of questions from the previous tool; and (b) addition of new questions on sensory symptoms. The modified tool was validated against DSM-5 diagnostic criteria. In addition, receiver operating characteristic (ROC) curves were used to determine the cut-off for total score as compared to Childhood Autism Rating Scale (CARS) score to grade the severity of ASD. Two-hundred-twenty-five children (159 boys, median age = 47months) were enrolled. The modified tool demonstrated sensitivity of 98.4% and specificity of 91.7% to diagnose ASD. A score ?14 on the tool was suggestive of severe ASD (CARS>36.5) with a sensitivity and specificity of 80% and 80.7% respectively [Area under the curve = 0.89]. AIIMS-Modified-INDT-ASD Tool is a simple and structured instrument based on DSM-5 criteria which can facilitate diagnosis of ASD with acceptable diagnostic accuracy. | [
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The objective of the study was to evaluate role of zeolite and Enterobacter sp. MN17 on Cd uptake, growth, physiological and biochemical responses of Brassica napus on Cd-contaminated soil. A sandy clay loam soil in plastic pots was spiked with Cd (0 and 80 mg kg-1) and amended with zeolite (0 and 10 g kg-1). Seeds of B. napus were inoculated with Enterobacter sp. MN17. Both inoculated and non-inoculated seeds of B. napus were sown and plants were harvested after 60 days of growth and data were collected. Although sole application of zeolite and seed inoculation reverted adverse effects of Cd in B. napus plants, the combined use resulted in even higher growth and physiological responses compared to control plants. The combined use under Cd stress increased plant height, root length, dry biomass of shoot and root up to 32%, 57%, 42% and 64%, respectively compared to control. The different physiological attributes (photosynthetic rate, chlorophyll content, transpiration rate, stomatal conductance) of B. napus were improved from 6% to 137%. Moreover, combined use of zeolite and seed inoculation on Cd-contaminated soil reduced the stress to plants as antioxidant activities decreased up to 25-64%, however enzyme activities were still higher than plants grown on normal soil. Root and shoot analysis of B. napus for Cd content depicted that zeolite and bacterium decreased Cd uptake from soil. It is concluded that combined use of zeolite and strain MN17 reduces Cd uptake from soil and improves physiological and biochemical responses of B. napus which is helpful to alleviate Cd toxicity to plants. | [
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BACKGROUND: It is imperative to address the health problems faced by immigrants in their destination countries in light of the current magnitude of migration processes worldwide. We aimed to evaluate the socioeconomic determinants of healthcare utilization in immigrants with depression.METHOD: A population-based cohort comprising all immigrants who were eligible for National Health Insurance coverage (permanent residents, marriage immigrants, and naturalized citizens) using the National Health Insurance Claims Database in 2011-2013 was established. Cases were defined as immigrants with new-onset depression. Controls were new-onset Korean patients with depression matched by age, sex, and Charlson comorbidity index in a 1:2 ratio. Appropriateness of care (AOC) was defined as visiting a clinic for depression management at least 3 times in the first 12 weeks and 4 times thereafter until 12 months post-cohort entry.RESULTS: A total of 2,378 immigrants and 4,756 matched Korean patients were identified. Of the immigrants, 30.0% achieved AOC, in contrast to 38.7% of Koreans (p < .0001). Adjusting for possible covariates, AOC was less likely for immigrants (adjusted OR (aOR), 0.760; 95% CI: 0.670-0.863). Medical Aid (aOR, 2.309; 95% CI, 1.479-3.610), rural residence (aOR, 1.536; 95% CI, 1.054-2.237), the presence of a psychiatric comorbidity (aOR, 1.912; 95% CI, 1.484-2.463), and visiting a psychiatrist (aOR, 2.387; 95% CI, 1.821-3.125) were associated with an increased likelihood of AOC in immigrants.CONCLUSION: Socioeconomic determinants included insurance type (Medical Aid and National Health Insurance), place of residence, psychiatric comorbid status, doctor specialty, easy access to medical services (clinic-based), and a SSRI-based treatment regimen. Those predictors should be taken into account when developing healthcare strategies for immigrants. | [
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OBJECTIVE: This study evaluated whether frequent (fortnightly) audit and feedback cycles over a sustained period of time (>12 months) increased clinician adherence to recommended guidelines in acquired brain injury rehabilitation.DESIGN: A before and after study design.SETTING: A metropolitan inpatient brain injury rehabilitation unit.PARTICIPANTS: Clinicians; medical, nursing and allied health staff.INTERVENTIONS: Fortnightly cycles of audit and feedback for 14 months. Each fortnight, medical file and observational audits were completed against 114 clinical indicators.MAIN OUTCOME MEASURE: Adherence to guideline indicators before and after intervention, calculated by proportions, Mann-Whitney U and Chi square analysis.RESULTS: Clinical and statistical significant improvements in median clinical indicator adherence were found immediately following the audit and feedback program from 38.8% (95% CI 34.3 to 44.4) to 83.6% (95% CI 81.8 to 88.5). Three months after cessation of the intervention, median adherence had decreased from 82.3% to 76.6% (95% CI 72.7 to 83.3, p<0.01). Findings suggest that there are individual indicators which are more amenable to change using an audit and feedback program.CONCLUSION: A fortnightly audit and feedback program increased clinicians' adherence to guideline recommendations in an inpatient acquired brain injury rehabilitation setting. We propose future studies build on the evidence-based method used in the present study to determine effectiveness and develop an implementation toolkit for scale-up. | [
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] |
Soil is the medium that balances the soil and water pressure on the excavation surface of an earth pressure balance (EPB) shield machine, and the soil flow plasticity directly affects the working performance of the shield machine. The spiral shear stress is the main determinant of the soil flow plasticity. During the progress of the EPB shield screw conveyor normal operation, the shear effects between the muck in the spiral tube and the screw shaft, as well as the flight, are different from the shear action, such as the direct shear or the vane shear. The direct or vane shear test is now widely used to evaluate soil flow plasticity. To better investigate the shear properties between the soil and the shield conveyor casing, a model screw conveyor was developed. Based on the analysis of the stress conditions and the movement of the conditioned soil plug, the theoretical calculation model of the equivalent helical shear stress of the EPB shield screw conveyor was deduced based on the steady-state equilibrium conditions of moment of momentum. The conditioned standard sand was used in the indoor tests. The results of the indoor test of the model machine verified the rationality and effectiveness of the theoretical model. The model provides an important theoretical basis and references for the design and optimization of soil conditioning during shield tunneling. | [
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BACKGROUND: Amputation for longstanding therapy resistant complex regional pain syndrome type-I (CRPS-I) is controversial. Reported results are inconsistent. It is assumed that psychological factors play a role in CRPS-I.OBJECTIVE: To explore which psychological factors prior to amputation are associated with poor outcomes after amputation in the case of longstanding therapy resistant CRPS-I.METHODS: Between May 2008 and August 2015, 31 patients with longstanding therapy resistant CRPS-I were amputated. Before the amputation 11 psychological factors were assessed. In 2016, participants had a structured interview by telephone and filled out questionnaires to assess their outcome. In case of a perceived recurrence of CRPS-I a physician visited the patient to examine the symptoms. Associations between psychological factors and poor outcomes were analysed.RESULTS: Four of the 11 psychological factors were associated with poor outcomes. Regression analyses showed that change in the worst pain in the past week was associated with poor social support (B = 0.3, 95% confidence interval: 0.1;0.6) and intensity of pain before amputation (B = 2.0, 95% confidence interval 0.9;3.0). Patients who reported important improvements in mobility (n = 23) had significantly higher baseline resilience (median 79) compared to those (n = 8) who did not report it (median 69)(Mann-Whitney U, Z = -2.398, p = 0.015). Being involved in a lawsuit prior to amputation was associated with a recurrence in the residual limb (Bruehl criteria). A psychiatric history was associated with recurrence somewhere else (Bruehl criteria).CONCLUSION: Poor outcomes of amputation in longstanding therapy resistant CPRS-1 are associated with psychological factors. Outstanding life events are not associated with poor outcome although half of the participants had experienced outstanding life events. | [
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] |
Cutaneous squamous cell carcinomas are a common form of highly mutated keratinocyte skin cancers that are of particular concern in immunocompromised patients. Here we report on the efficacy of topically applied MS-275, a clinically used histone deacetylase inhibitor, for the treatment and management of this disease. At 2 mg/kg, MS-275 significantly decreased tumor burden in an SKH-1 hairless mouse model of UVB radiation-induced skin carcinogenesis. MS-275 was cell permeable as a topical formulation and induced histone acetylation changes in mouse tumor tissue. MS-275 was also effective at inhibiting the proliferation of patient derived cutaneous squamous cell carcinoma lines and was particularly potent toward cells isolated from a regional metastasis on an immunocompromised individual. Our findings support the use of alternative routes of administration for histone deacetylase inhibitors in the treatment of high-risk squamous cell carcinoma which may ultimately lead to more precise delivery and reduced systemic toxicity. | [
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] |
There is evidence to suggest that abnormal angiogenesis, inflammation, and fibrosis drive diabetic nephropathy (DN). However, there is no specific treatment to counteract these processes. We aimed to determine whether DIAVIT, a natural Vaccinium myrtillus (blueberry) and Hippophae Rhamnoides (sea buckthorn) extract, is protective in a model of type II DN. Diabetic db/db mice were administered DIAVIT in their drinking water for 14 weeks. We assessed the functional, structural, and ultra-structural phenotype of three experimental groups (lean+vehicle, db/db+vehicle, db/db+DIAVIT). We also investigated the angiogenic and fibrotic pathways involved in the mechanism of action of DIAVIT. Diabetic db/db mice developed hyperglycaemia, albuminuria, and an increased glomerular water permeability; the latter two were prevented by DIAVIT. db/db mice developed fibrotic glomeruli, endothelial insult, and glomerular ultra-structural changes, which were not present in DIAVIT-treated mice. Vascular endothelial growth factor A (VEGF-A) splicing was altered in the db/db kidney cortex, increasing the pro-angiogenic VEGF-A165 relative to the anti-angiogenic VEGF-A165b. This was partially prevented with DIAVIT treatment. Delphinidin, an anthocyanin abundant in DIAVIT, increased the VEGF-A165b expression relative to total VEGF-A165 in cultured podocytes through phosphorylation of the splice factor SRSF6. DIAVIT, in particular delphinidin, alters VEGF-A splicing in type II DN, rescuing the DN phenotype. This study highlights the therapeutic potential of natural drugs in DN through the manipulation of gene splicing and expression. | [
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In response to the Fukushima Daiichi nuclear power plant disaster, the Nuclear Regulation Authority of Japan issued the new "Nuclear Emergency Response Guideline." However, there is a perception that scientific information about the health impact of radiation exposure has not been adequately shared among the local government staffs, including schoolteachers. We contacted schoolteachers at all 120 schools within the Urgent Protective Action Planning Zone of the Sendai Nuclear Power Plant, Kagoshima prefecture, in 2017. We invited them to take part in a written survey to clarify their concerns and risk perceptions regarding the effects of radiation exposure on health. Five hundred and fifty schoolteachers' replies were included in the analysis. The results revealed that 355 schoolteachers had concerns about the health effects of radiation exposure due to working within the Urgent Protective Action Planning Zone. A logistic regression analysis revealed that sex (OR = 2.26, 95% CI: 1.49-3.45, p < 0.001), age (OR = 3.39, 95% CI: 2.10-5.47, p < 0.001), reluctance to undergo a radiological examination at a hospital (OR = 1.91, 95% CI: 1.23-2.88, p = 0.004), place of work (OR = 2.18, 95% CI: 1.46-3.27, p < 0.001), and anxiety about having to address questions about radiation from students (OR = 4.66, 95% CI: 2.83-7.67, p < 0.001) were independently associated with schoolteachers' concerns about the health effects of radiation exposure due to working in the area around the nuclear power plant. Therefore, it is important to respond to these concerns in order to establish a meaningful education program for school children on radiation and its health effects. | [
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] |
Canine CD4+CD8+ double-positive (dp) T cells of peripheral blood are a unique effector memory T cell subpopulation characterized by an increased expression of activation markers in comparison with conventional CD4+ or CD8+ single-positive (sp) T cells. In this study, we investigated CD4+CD8+ dp T cells in secondary lymphatic organs (i.e. mesenteric and tracheobronchial lymph nodes, spleen, Peyer's patches) and non-lymphatic tissues (i.e. lung and epithelium of the small intestine) within a homogeneous group of healthy Beagle dogs by multi-color flow cytometry. The aim of this systematic analysis was to identify the tissue-specific localization and characteristics of this distinct T cell subpopulation. Our results revealed a mature extrathymic CD1a-CD4+CD8+ dp T cell population in all analyzed organs, with highest frequencies within Peyer's patches. Constitutive expression of the activation marker CD25 is a feature of many CD4+CD8+ dp T cells independent of their localization and points to an effector phenotype. A proportion of lymph node CD4+CD8+ dp T cells is FoxP3+ indicating regulatory potential. Within the intestinal environment, the cytotoxic marker granzyme B is expressed by CD4+CD8+ dp intraepithelial lymphocytes. In addition, a fraction of CD4+CD8+ dp intraepithelial lymphocytes and of mesenteric lymph node CD4+CD8+ dp T cells is TCR+. However, the main T cell receptor of all tissue-associated CD4+CD8+ dp T cells could be identified as TCR. Interestingly, the majority of the CD4+CD8+ dp T cell subpopulation expresses the unconventional CD8 homodimer, in contrast to CD8+ sp T cells, and CD4+CD8+ dp thymocytes which are mainly CD8+. The presented data provide the basis for a functional analysis of tissue-specific CD4+CD8+ dp T cells to elucidate their role in health and disease of dogs. | [
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Light driven primary production by plants is the main source of biomass in terrestrial ecosystems. But also in subsurface habitats like aquifers, life is fueled largely by this plant-derived biomass. Here, we investigate the degradation of plant-derived polysaccharides in a groundwater microbiome to identify the microbial key players involved, and compare them to those from soil of the groundwater recharge area. We quantified the activities of enzymes degrading the abundant plant polymers starch, cellulose and hemicellulose in oligotrophic groundwater samples, despite the low cell numbers present. Normalized to 16S rRNA gene copy numbers, these activities were only one order of magnitude lower than in soil. Stimulation of the groundwater microbiome with either starch or cellulose and hemicellulose led to changes of the enzymatic activity ratios, indicating autochthonous production of enzymes in response to the plant polymers. Furthermore, DNA stable isotope probing with 13C labelled plant polymers allowed us to identify microbes involved in the degradation of these compounds. In (hemi)cellulose microcosms, Bacteroidia and Candidatus Parcubacteria were active, while the active community in starch microcosms mostly comprised Candidatus Saccharibacteria, Cytophagia, and Actinobacteria. Not a single one of the active OTUs was also found to be labelled in soil microcosms. This indicates that the degradation of plant-derived polysaccharides in groundwater is driven by organisms completely distinct from those active in soil. The involvement of members of the candidate phyla Cand. Parcubacteria and Cand. Saccharibacteria, organisms known to be abundant in groundwater, in plant-derived organic matter degradation might strongly impact subsurface carbon cycling. | [
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] |
Gentrification is multidimensional and complex, but there is general agreement that visible changes to neighbourhoods are a clear manifestation of the process. Recent advances in computer vision and deep learning provide a unique opportunity to support automated mapping or 'deep mapping' of perceptual environmental attributes. We present a Siamese convolutional neural network (SCNN) that automatically detects gentrification-like visual changes in temporal sequences of Google Street View (GSV) images. Our SCNN achieves 95.6% test accuracy and is subsequently applied to GSV sequences at 86110 individual properties over a 9-year period in Ottawa, Canada. We use Kernel Density Estimation (KDE) to produce maps that illustrate where the spatial concentration of visual property improvements was highest within the study area at different times from 2007-2016. We find strong concordance between the mapped SCNN results and the spatial distribution of building permits in the City of Ottawa from 2011 to 2016. Our mapped results confirm those urban areas that are known to be undergoing gentrification as well as revealing areas undergoing gentrification that were previously unknown. Our approach differs from previous works because we examine the atomic unit of gentrification, namely, the individual property, for visual property improvements over time and we rely on KDE to describe regions of high spatial intensity that are indicative of gentrification processes. | [
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OBJECTIVE: Very preterm (<32 weeks gestation; VP) and/or very low birth weight (<1500g; VLBW) children often have cognitive and mathematic difficulties. It is unknown whether VP/VLBW children's frequent mathematic problems significantly add to the burden of negative life-course consequences over and above effects of more general cognitive deficits. Our aim was to determine whether negative consequences of VP/VLBW versus healthy term birth on adult wealth are mediated by mathematic abilities in childhood, or rather explained by more general cognitive abilities.METHODS: 193 VP/VLBW and 217 healthy term comparison participants were studied prospectively from birth to adulthood as part of a geographically defined study in Bavaria (South Germany). Mathematic and general cognitive abilities were assessed at 8 years with standardized tests; wealth information was assessed at 26 years with a structured interview and summarized into a comprehensive index score. All scores were z-standardized.RESULTS: At 8 years, VP/VLBW (n = 193, 52.3% male) had lower mathematic and general cognitive abilities than healthy term comparison children (n = 217, 47.0% male). At 26 years, VP/VLBW had accumulated significantly lower overall wealth than term born comparison adults (-0.57 (1.08) versus -0.01 (1.00), mean difference 0.56 [0.36-0.77], p < .001). Structural equation modeling confirmed that VP/VLBW birth ( = -.13, p = .022) and childhood IQ ( = .24, p < .001) both directly predicted adult wealth, but math did not ( = .05, p = .413). Analyses were controlled for small-for-gestational-age (SGA) birth, child sex, and family socioeconomic status.CONCLUSION: This longitudinal study from birth to adulthood shows that VP/VLBW survivors' general cognitive rather than specific mathematic problems explain their diminished life-course success. These findings are important in order to design effective interventions at school age that reduce the burden of prematurity for those individuals who were born at highest neonatal risk. | [
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Acianthera section Pleurobotryae is one of ten sections of the genus Acianthera and include four species endemic to the Atlantic Forest. The objective of this study was to describe comparatively the anatomy of vegetative organs and floral micromorphology of all species of Acianthera section Pleurobotryae in order to identify diagnostic characters between them and synapomorphies for the section in relation of other sections of the genus. We analyzed roots, ramicauls, leaves and flowers of 15 species, covering eight of the nine sections of Acianthera, using light microscopy and scanning electron microscopy. Acianthera section Pleurobotryae is a monophyletic group and the cladistic analyses of anatomical and flower micromorphology data, combined with molecular data, support internal relationship hypotheses among the representatives of this section. The synapomorphies identified for A. sect. Pleurobotryae are based on leaf anatomy: unifacial leaves, round or elliptical in cross-section, round leaves with vascular bundles organized in concentric circles, and mesophyll with 28 to 30 cell layers. Within the section, the clade (A. crepiniana + A. mantiquyrana) presented more differences in vegetative organ morphology and higher support values in combined analyses when compared to the second clade, (A. atropurpurea + A. hatschbachii). For each of these clades an exclusive set of homoplasies of vegetative and floral organs were also identified. The results support the argument that vegetative organs are more evolutionarily stable in comparison to reproductive organs and thus helpful for inference of internal phylogenetic relationships in Acianthera, while flowers are highly variable, perhaps due to the diversity of pollinator attraction mechanisms. The analyses indicate that the elliptical leaves observed in A. crepiniana have originated from round leaves observed in the other species of this section, suggesting an adaptation to increase the area of exposure of the leaf and better the efficiency of capture of sunlight in shaded environments such as the Atlantic Forest. The presence of papillose regions in both vegetative and floral organs indicated that micromorphological characters are also useful for the delimitation of species and sections within the genus. | [
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] |
OBJECTIVES: With HIV treatment as a prevention strategy, retention in care remains a key for sustained viral suppression. We sought to identify HIV-infected patients at risk for medical care interruption (MCI) in a high-income country.METHODS: The HIV-infected patients enrolled had to attend the clinic at least twice between January 2010 and October 2014 and were followed up until May 2016. MCI was defined as patients not seeking care in or outside the clinic for at least 18 months, regardless of whether they returned to care after the interruption. The association between MCI and sociodemographic, clinical, and immuno-virological characteristics at HIV diagnosis and during follow-up was assessed using Cox models.RESULTS: The incidence rate of MCI was 2.5 per 100 persons-years (95% confidence interval [CI] = 2.3-2.7). MCI was more likely in patients who accessed care >6 months after diagnosis (hazard ratio [HR] = 1.30, 95% CI = 1.10-1.54 vs. ?6 months) or did not report a primary care physician (HR = 2.40; 95% CI = 2.03-2.84). MCI was less likely in patients born in sub-Saharan Africa (HR = 0.75, 95% CI = 0.62-0.91 vs. born in France). During follow-up, the risk of MCI increased when the last CD4 count was ?350 (HR = 2.85, 95% CI = 2.02-4.04 vs. >500 cells/mm3) and when the patient was not on antiretroviral therapy (HR = 3.67, 95% CI = 2.90-4.66).CONCLUSIONS: The incidence of MCI is low in this hospital that serves a large proportion of migrants. Low or no recorded CD4 counts for a medical visit could alert of a higher risk of MCI, even more in patients who accessed HIV care late or did not report a primary care physician. | [
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The general decline of seabird populations worldwide raises large concerns. Although multiple factors are interacting to cause the observed trends, increased mortality from incidental bycatch in fisheries has proven to be important for many species. However, the bulk of published knowledge is derived from longline fisheries, whereas bycatch in gillnet fisheries is less studied and even overlooked in some areas. We present seabird bycatch data from a 10-year time-series of fishery data from the large fleet of small-vessels fishing with gillnets along the Norwegian coast-a large area and fishery with no prior estimates of seabird bycatch. In general, we document high rates of incidental bycatch (averaging 0.0023 seabirds/net, or approximately 0.08 seabirds/fishing trip). This results in an estimated annual bycatch between 1580 and 11500 (95% CI) birds in this fishery. There was a surprisingly high percentage (43%) of surface-feeding seabirds in the bycatch, with northern fulmar being the most common species. Among the diving seabirds caught, common guillemot was most numerous. Our findings suggest that coastal gillnet fisheries represent a more general threat to a wider range of seabird populations, as opposed to longline fisheries where surface-feeding seabird species seem to dominate the bycatch. The bycatch estimates for the Norwegian gillnet-fishery varied in time, between areas, and with fishing depth and distance from the coast, but we found no clear trends in relation to the type of gillnets used. The results enabled us to identify important spatio-temporal trends in the seabird bycatch, which can allow for the development and implementation of more specific mitigation measures. While specific time closures might be an efficient option to reduce bycatch for diving seabirds, measures such as gear modification and reduction in release of wastewater during fishing operation are probably a more effective mitigation approach for reducing bycatch of surface-feeding seabirds. | [
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] |
OBJECTIVES: To investigate treatment outcomes and associated characteristics of persons experiencing homelessness who received 12-weekly doses of directly observed isoniazid and rifapentine (3HP/DOT) treatment for latent TB infection (LTBI).METHODS: Among homeless persons treated with 3HP/DOT during July 2011 -June 2015 in 11 U.S. TB programs, we conducted descriptive analyses of observational data, and identified associations between sociodemographic factors and treatment outcomes. Qualitative interviews were conducted to understand programmatic experiences.RESULTS: Of 393 persons experiencing homelessness (median age: 50 years; range: 13-74 years), 301 (76.6%) completed treatment, 55 (14.0%) were lost to follow-up, 18 (4.6%) stopped because of an adverse event (AE), and 19 (4.8%) stopped after relocations or refusing treatment. Eighty-one (20.6%) had at least one AE. Persons aged ?65 were more likely to discontinue treatment than persons aged 31-44 years. Programs reported difficulty in following up with persons experiencing homelessness because of relocations, mistrust, and alcohol or drug use.CONCLUSIONS: This study demonstrates the feasibility of administering the 3HP/DOT LTBI regimen to persons experiencing homelessness, a high-risk population. | [
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With warmer springs, herbivores migrating to Arctic breeding grounds may experience phenological mismatches between their energy demands and the availability of high quality forage. Yet, how the timing of the start of the season and herbivore arrival influences forage quality is often unknown. In coastal western Alaska, approximately one million migratory geese arrive each spring to breed, where foliar %N and C:N ratios are linked to gosling survival and population growth. We conducted a three-year experiment where we manipulated the start of the growing season using warming chambers and grazing times using captive Pacific black brant (Branta bernicla nigricans) to examine how the timing of these events influences the quality of an important forage species. Our results suggest that grazing timing plays a much greater role than an advanced growing season in determining forage quality. All top models included grazing timing, and suggested that compared to typical grazing timing, early grazing significantly reduced foliar %C by 6% and C:N ratios by 16%, while late goose grazing significantly reduced foliar %N by 15% and increased foliar C:N ratios by 21%. While second-ranking top models included the effect of season, the advanced growing season effect was not significant and only reduced %N by 4%, increased %C by <1%, and increased C:N ratios by 5% compared to an ambient growing season. In summary, in years where geese arrive early, they will consume higher quality forage when they arrive and throughout the season, while in years that geese arrive late they will consume lower quality forage when they arrive and for the remainder of the season. When the growing season starts has only a minor influence on this pattern. Our findings suggest that cues determining migration and arrival times to breeding areas are important factors influencing forage quality for geese in western Alaska. | [
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INTRODUCTION: Antimicrobial resistance (AMR) is a major global health challenge. Pharmacists play a key role in the health care setting to support the quality use of medicines. The education and training of pharmacy students have the potential to impact on patterns of antibiotic use in community and hospital settings. The aim of this study was to investigate and compare antibiotic use and knowledge of antibiotics and AMR among undergraduate pharmacy students in Australian and Sri Lankan universities.METHODS: A cross-sectional survey was conducted in Australian and Sri Lankan universities that offer a pharmacy degree. A paper-based survey was utilised in Sri Lanka and an identical survey distributed online among pharmacy students in Australia. Descriptive and comparative data analyses were performed.RESULTS: 476 pharmacy students from 14 universities in Australia and 466 students from 6 universities in SL completed the survey. Participants commonly reported previous antibiotic use [Australia (88%) and Sri Lanka (86%)]. The majority of students [Australia (89%) and Sri Lanka (77%)] reported they obtained antibiotics with a prescription. Australian pharmacy students correctly reported regarding optimal antibiotic use for certain disease conditions when compared to Sri Lankan students (P<0.05). A greater antibiotic knowledge level regarding AMR was found among Australian students compared to Sri Lankan students (p<0.05).CONCLUSION: This study provides an understanding about antibiotic consumption and knowledge on AMR among pharmacy students in a developed country, Australia and a developing country, Sri Lanka. These findings identify possible misconceptions about antibiotics and a lower level of knowledge of AMR amongst Sri Lankan undergraduate pharmacy students. Future research should focus on implementation of a strategic education plan for undergraduate pharmacy students in Sri Lankan universities. The curricula of pharmacy courses in Australian universities may inform such a plan. | [
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A novel method by hyphenating chip-based array ion-imprinted monolithic microextraction with inductively coupled plasma mass spectrometry (ICP-MS) was proposed for the online analysis of trace Gd in biological samples in this work. The poly(-methacryloxypropyltrimethoxysilane@Gd3+-surface ion-imprinted polymer) [poly(-MAPS@Gd3+-SIIP)] monolithic capillary was prepared via in situ polymerization on the vinyl-modified surface of poly(-MAPS) using Eu3+ as the mimic template. The prepared ion-imprinted monolithic capillary possessed higher selectivity and adsorption capacity to Gd3+ than the non-imprinted monolithic capillary. Eight poly(-MAPS@Gd3+-SIIP) monolithic capillaries were embedded in the channels of a microfluidic chip to fabricate a chip-based array microextraction device. Factors affecting the selectivity of the prepared ion-imprinted monolithic capillary including imprinted time and the composition of the prepolymerization solution, and extraction conditions for the fabricated chip-based array ion-imprinted monolithic capillary microextraction platform were optimized. A sample throughput of 18 h-1 was achieved along with a low detection limit of 1.27 ng L-1 for Gd3+. The proposed chip-based array poly(-MAPS@Gd3+-SIIP) monolithic microextraction-ICP-MS method was used for the analysis of trace Gd in human urine and serum, and the recovery for spiking experiments was in the range of 88.1-96.7%. The developed integrated analysis platform possesses good interference resistance, high automation, high sensitivity and low consumption of the sample/agent, which makes it very suitable for the analysis of trace elements in complicated biological samples. | [
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Fourier transform infrared spectroscopy (FTIR) has been shown to be a promising tool for identifying the mode of action of drugs. However, most previous studies have focused on the analysis of fixed or dried cells. The measurement of living cells has the advantage of obtaining time series data, and the in situ approach eliminates the need for fixing or drying the cells. In this study, the potential of live-cell FTIR method for the identification of the mode of action of drugs was demonstrated. Four different drugs were tested, with two of the drugs having the same mode of action (tamoxifen and toremifene) and the other two having different modes of action (imatinib and doxorubicin). Live cells were treated in the four drugs at and below the IC50 level (i.e. the concentration of drug required to inhibit the growth of cells by 50%), and the changes to their spectra after the addition of drugs were monitored over a 24-hour period. Principal component analysis (PCA) of the spectral data shows that drugs with different modes of action are well-separated, while the drugs with the same mode of action are grouped together. The results also show that at IC50, the separation appears to be the clearest at 2 hours for imatinib and tamoxifen/toremifene and 6 hours for doxorubicin. However, at 50% of the IC50 drug concentration, the separation appears to be the best at longer incubation time, i.e. 24 hours, for all four drugs. In conclusion, live-cell FTIR has shown to be able to distinguish and group spectral signatures of cells treated with drugs of known modes of action after a relatively short time of exposure. Further collection of live-cell data would enable an algorithm to be developed for the prediction of the modes of action of novel drugs, which can help in the preclinical drug screening process. | [
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Leaves of Cyclocarya paliurus (CP) have a potential antihyperglycemic effect, but its active compositions responsible for the beneficial properties remain unclear. The CP extract exhibited remarkable -glucosidase inhibitory activity with an IC50 value of 31.5 1.05 g mL-1, much lower than that of the positive control acarbose (IC50 = 296.6 1.06 g mL-1). To identify the specific -glucosidase inhibitors from the CP extract, affinity ultrafiltration coupled with ultra-performance liquid chromatography and quadrupole-time-of-flight mass spectrometry (UF-UPLC-Q/TOF-MS/MS) was developed and 11 potential -glucosidase inhibitors from CP extract were identified. In vitro -glucosidase inhibitory assay verified that quercetin-3-O-glucuronide, kaempferol-3-O-rhamnoside, quercetin, kaempferol, asiatic acid and genistein were primarily responsible for the -glucosidase inhibitory activity of the CP extract. Further, a hypoglycemia test also verified that these -glucosidase inhibitors had the potential to reduce post-prandial hyperglycaemia in C57BL/6 mice. Moreover, the molecular docking study revealed that these identified -glucosidase inhibitors more easily occupy the active sites of -glucosidase than does the positive control acarbose. These findings suggest the CP tea leaves are the potential source of a hypoglycaemic agent. | [
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] |
Measurements of neutrophil activities such as cell migration and phagocytosis are generally performed using low-content bulk assays, which provide little detail activity at the single cell level, or flow cytometry methods, which have the single cell resolution but lack perspective on the kinetics of the process. Here, we present a microfluidic assay for measuring the essential functions that contribute to the antimicrobial activity of neutrophils: migration towards the target, and killing of microbes. The assay interrogates the interactions between isolated human neutrophils and populations of live, proliferating microbes. The outcome is measured in a binary mode that is reflective of in vivo infections, which are either cleared or endure the host response. The outcome of the interactions is also characterized at single cell resolution for both the neutrophils and the microbes. We applied the assay to test the response of neutrophils from intensive care patients to live Staphylococcus aureus, and observed alterations of antimicrobial neutrophil activity in patients, including those with sepsis. By directly measuring neutrophil activity against live targets at high spatial and temporal resolution, this assay provides unique insights into the life-or-death contest shaping the outcome of interactions between populations of neutrophils and microbes. | [
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Separately, Fenton and starvation cancer therapies have been recently reported as impressive methods for tumor destruction. Here, we introduce natural hemoglobin and glucose oxidase (GOx) for efficient cancer treatment following combined Fenton and starvation therapies. GOx and hemoglobin were encapsulated in zeolitic imidazolate frameworks 8 (ZIF-8) to fabricate a pH-sensitive MOF activated by tumor acidity. In the slightly acidic environment of cancer cells, GOx is released and it consumes d-glucose and molecular oxygen, nutrients essential for the survival of cancer cells, and produces gluconic acid and hydrogen peroxide, respectively. The produced gluconic acid increases the acidity of the tumor microenvironment leading to complete MOF destruction and enhances hemoglobin and GOx release. The Fe ions from the heme groups of hemoglobin also release in the presence of both endogenous and produced H2O2 and generate hydroxyl radicals. The produced OH? radical can rapidly oxidize the surrounding biomacromolecules in the biological system and treat the cancer cells. In vitro experiments demonstrate that this novel nanoparticle is cytotoxic to cancer cells HeLa and MCF-7, at very low concentrations (<2 g mL-1). In addition, the selectivity index values are 5.52 and 11.04 for HeLa and MCF-7 cells, respectively, which are much higher than those of commercial drugs and those of similar studies reported by other research groups. This work thus demonstrates a novel pH-sensitive system containing hemoglobin and GOx for effective and selective cancer treatment using both radical generation and nutrient starvation. | [
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] |
The objective of this article is to present 3 various types of gummy smile treated with botulinum toxin-A injection per site at Yonsei points. The patients, who visited the department to demand a more aesthetic smile, were classified according to gummy smile type: asymmetric, anterior, and mixed. Botulinum toxin-A injection at Yonsei point was considered. Preinjection and postinjection pictures were taken, and the severity of excessive gingival display was measured for each tooth between second premolars. Two weeks after botulinum toxin injections, no complication was noted. The amount of excessive gingival display for each tooth between second premolars was measured less than 3 mm, and the percentage of improvement for each case was calculated 100%. The botulinum toxin injection at Yonsei point may be a predictable and noninvasive treatment option for various types of gummy smile. | [
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The aim of this report was to describe an approach for a child with phakomatosis pigmentovascularis Type IIb associated with bilateral Sturge-Weber syndrome and autistic spectrum disorder. A 6-year-old boy was referred to the Special Care Dental Clinic with the main complaints of "damaged teeth and pain." The physical examination revealed bilateral port-wine staining on the face, neck, and upper and lower limbs, congenital dermal melanocytosis on the back, and dilated blood vessels in the sclera. Intraoral examination revealed hypertrophy of the maxillary bone, diffuse and intense redness of the oral mucosa, crowding, anterior open bite, and carious lesions in the left and right upper second primary molars. The medical team was consulted prior to dental treatment to assess the risk of bleeding, and anesthesia was contraindicated. Instruction about brushing technique and procedures for a suitable oral environment were then carried out using a minimally invasive restorative treatment. The patient did not exhibit collaborative behavior, and follow up continues with the patient receiving preventive treatments. Therefore, a multidisciplinary approach to these patients is fundamental to avoid complications during dental intervention. Moreover, regular visits to the dentist reduce the need for invasive treatments and improve the well-being of these individuals. | [
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AIM: To describe operating theatre nurses' experience of preconditions for safe intraoperative nursing care and teamwork.BACKGROUND: Surgical interventions are often needed for patients' well-being and survival from health problems. Adequate information to professionals responsible within the surgical organisation is of importance for patient safety in connection to the surgery. The members in the surgical team need correct information about the patients' health and planned care. The information is mainly transferred by computerised systems that do not necessarily provide all information needed.METHOD: A qualitative descriptive design was chosen. Narrative interviews were carried out with 16 experienced operating theatre nurses in four different hospitals in rural and urban areas in Sweden. The data were analysed using qualitative content analysis. The study complied with criteria to Consolidated Criteria for Reporting Qualitative Research (COREQ).RESULT: Operating theatre nurses strived to get adequate information about the patients' care, the surgical intervention and the equipment to be well prepared for intraoperative nursing care. The information from the computerised systems was described as fragmented and obliged the operating theatre nurses to demand a preoperative dialogue between the members of the surgical team. Professional collegial teamwork and committed leadership were considered to enhance patient safety.CONCLUSION: From the operating theatre nurses' perspective, prerequisites for intraoperative safe nursing care and teamwork depend upon a preoperative dialogue between the members in the surgical team for collegial teamwork, obtaining a reliable preoperative overall picture based on adequate information transfer, and the support of a committed first-line manager.RELEVANCE TO CLINICAL PRACTICE: The operating theatre nurses need a reliable preoperative overall picture in advance, to be able to be well prepared for the patients' surgery. The overall picture should be based on adequate data about the patients' health status and needs, details about the surgical intervention and prescriptions. | [
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] |
OBJECTIVES: Surgical site infections (SSIs) result in significant negative clinical and economic outcomes. The objective of this study is to estimate annual health expenditures associated with spinal cord stimulation (SCS)-related infections.MATERIALS AND METHODS: Data from the Truven MarketScan databases were used to identify patients with an SCS implant (2009-2014) and a continuous health plan enrollment for at least 12-months before and after implant (index date). Annual expenditures were estimated for patients with a device-related infection vs. those without infection since index date. A generalized linear model estimated annual expenditures attributable to device-related infection. Multivariable expenditure models were conducted separately for patients in initial and replacement groups, controlling for demographics, comorbidities, and clinical characteristics.RESULTS: The study included 6615 patients. Multivariable expenditure models revealed that patients with infection have higher annual expenditures than patients without infection. Estimated incremental annual healthcare expenditures for patients with an infection were $59,716 (95% CI: $48,965-$69,480) for initial implanted patients and $64,833 (95% CI: $37,377-$86,519) for replacement patients. Only 26% of patients who were explanted for infection underwent a reimplant.CONCLUSIONS: These results show the substantial expenditure burden associated with an SCS-related infection. Management of SCS-related infection is important from both clinical and economic standpoints. The economic and clinical data presented here reinforce the need for additional research and strategies for healthcare providers to minimize SCS infections. Future economic research is needed to further define the specific economic cost drivers associated with the extensive expenditure burden. | [
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This article explores how globalization reshapes moral development in northern Thailand. Employing a cultural-developmental approach to examine interview data gathered over the course of one year, the article discusses variations in Divinity-based moral reasoning among adolescents residing in variously globalized Thai communities. Quantitative analysis shows that moral reasoning diverges across contexts of globalization, with rural adolescents reasoning more in terms of the Ethic of Divinity than urban adolescents. Qualitative analysis shows how the meaning of Divinity diverges, with the Ethic of Divinity co-occurring alongside the Ethic of Community among rural adolescents, and the Ethic of Divinity co-occurring alongside the Ethic of Autonomy among urban adolescents. Analyses further indicate that rural and urban adolescents invoke distinct Divinity principles altogether. Findings suggest that in urban settings, Divinity is decontextualized from traditional community-driven Thai Buddhism and recontextualized to align with values that are adaptive in a globalized society. This article contributes to, and offers suggestions for, the empirical study of the moral psychology of globalization. | [
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] |
This study examines how two Korean adolescents, born in transnational marriage families, construct their identities in the context of globalization. The data used comes from a yearlong ethnographic research project that includes fieldnotes, interview transcripts, and additional artifacts. The findings reveal that Tayo and Sungho navigate through linguistically, culturally, and discursively hybridized social spaces. Encountering the ideology of a monoethnic, monolingual, and monocultural Korea, they suffer from pervasive social stigmatization of their heterogeneity. Yet over time, the two focal adolescents become critical social agents who understand intersubjective dynamics and use linguistic and cultural resources to re-imagine themselves in more symbolically powerful ways. The findings of this study capture the dialectic interaction between the global and the local. They urge researchers to focus further on the complexity, multiplicity, and fluidity of one's identity and to dig deeper into the lives of minority children. | [
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AIMS AND OBJECTIVES: To describe and understand strategies that oncological nurses use to support self-management of radiation-induced bowel and bladder issues in pelvic-cancer rehabilitation patients.BACKGROUND: Nurse-led self-management of radiation-induced bowel and bladder issues holds the potential to support cancer survivors.DESIGN: An ethnographic approach was applied in this study, which adhered to Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines.METHODS: Data collection was conducted in Sweden between October 2015-April 2018, involving observations of nurses' daily work, formal and informal interviews, individual and group interviews, and reviews of relevant documents used in the studied practice. Furthermore, 15 supportive nurse-patient talks were observed, and an ethnographic analysis was performed.RESULTS: The analysis identified the following three categories of nursing strategies that support self-management of radiation-induced bowel and bladder issues in pelvic-cancer rehabilitation patients: encouraging self-reflection, tailoring solutions together and keeping patients motivated. Nurses and patients jointly make sense of patients' symptoms using data that patients collect about themselves. Based on their shared understanding, they can co-create solutions to meet each individual patient's needs and develop routines to keep the patient motivated in performing the devised solutions.CONCLUSIONS: The results indicate that the strategies nurses use to support patients in self-management of radiation-induced bowel and bladder issues entail intertwining patients' experiences with their nurses' medical knowledge and specific clinical practice. Nurses' strategies build on their ability to connect patients' experiences and the elements of their own work practice.RELEVANCE TO CLINICAL PRACTICE: A deeper understanding of nurses' strategies to support self-management of radiation-induced bowel and bladder issues in pelvic-cancer rehabilitation patients can improve other self-management programmes, inform nurses' education and aid in the design of tools for pelvic-cancer rehabilitation support. | [
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AIMS: This study aimed to monitor development of spoilage-associated microbiota on high-oxygen modified atmosphere packaged (MAP) minced beef, assess diversity of Pseudomonas sp. therein employing a polyphasic approach and probe their ability to grow anaerobically in the presence of carbon dioxide.METHODS AND RESULTS: Headspace atmosphere and total viable count of MAP minced beef were monitored, and spoilage-associated microbiota was identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). Pseudomonas spp. represented a major part of the spoilage-associated microbiota throughout the spoilage process and were characterized with a polyphasic approach including MALDI-TOF, randomly amplified polymorphic DNA biotyping, 16S rDNA and rpoD sequence analysis, and carA multiplex polymerase chain reaction. Pseudomonas isolates displayed high diversity and varying assertiveness under conditions employed in MAP minced beef with P. fragi, P. lundensis and P. weihenstephanensis as dominant species.CONCLUSIONS: The polyphasic approach enabled high-throughput characterization of Pseudomonas sp. Their adapted capability to grow anaerobically and resistance to high levels of CO2 is suggested to be a general feature within the genus, which is hitherto underexplored.SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows that diverse Pseudomonas generally regarded as strict aerobes and CO2 -sensitive appear well adapted to grow under MAP conditions, leading to high cell counts in minced beef and ultimately contribute to spoilage of the product. | [
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The present article examines continuity and change in views on gender in a Maya community before and after a communication tower was installed in 2010. Interview data were collected in 2009 when participants were adolescents (n= 80) and then again in 2015 when they were young adults (n= 68). Values and beliefs for gender were measured using vignettes that were created through previous fieldwork (Manago, 2014). Young adults were also asked about their use of mobile phones and social media, and completed a social network mapping activity (Antonucci, 1986). Results showed continuities across time in self-expression values for gender roles and relations, which was predicted by high school attendance during adolescence. Young adult men and those who had been to high school were more likely to use the internet and Facebook. Internet use did not predict values beyond the effects of schooling; however, it predicted greater proportions of nonkin in participants' social network maps, which predicted greater self-expression values for gender relations. Qualitative analyses of participants' emic perspectives of the affordances of communication technologies illustrate how education and cultural values shape perceptions of the opportunities and risks of media use. | [
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] |
OBJECTIVES: To compare real-world characteristics and management of individuals aged 80 and older with heart failure (HF) and mid-range ejection fraction (HFmrEF) and heart failure with preserved ejection fraction (HFpEF) derived from a large cohort of survey and to compare them with those younger than 80 from the same survey.METHODS: This is an observational, multicentre and cross-sectional study conducted in Turkey (NCT03026114). Consecutive 1065 (mean age of 67.110.6years) patients admitted to the cardiology outpatient units with HFmrEF and HFpEF were included.RESULTS: Participants aged 80 and older (n=123, 11.5%) were more likely to be female (66.7% vs 52.5%, P=0.003), had a higher prevalence of atrial fibrillation (49.6% vs 34%, P=0.001), and anaemia (46.3% vs 33.4%, P=0.005) than those who were younger than 80. N-terminal pro B-type natriuretic peptide levels were higher in those aged 80 and older than in those younger than 80 (1037 vs 550pg/ml, P<0.001). The prescription rates of HF medications (including in ACE-Is/ARBs, -blockers, MRAs, digoxin, ivabradine and diuretics) were similar (P>0.05) in both groups. Octogenarians did not significantly differ from younger patients in the prevalence of HFmrEF (24.4% vs 22.9%) and HFpEF (75.6% vs 77.1%). Coronary artery disease was associated with HFmrEF (P<0.05), whereas atrial fibrillation was associated with HFpEF (P<0.05) in octogenarians.CONCLUSIONS: This study revealed that nearly 12% of the individuals with HFmrEF and HFpEF in this real-world sample were aged 80 and older. Participants aged 80 and older are more likely to be female and have more comorbidities than those who were younger than 80. However, HF medication profiles were similar in both groups. This study also showed that associated factors with HFmrEF and HFpEF were differ in octogenarians. | [
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] |
The term cybersex refers to the use of the Internet for sexual purposes (pornography, webcams, dating). While moderate use of cybersex could have a positive effect on sexual life, a small fraction of these cyber-users could have difficulties to control their consumption with negative consequences. This phenomenon, whose understanding of the mechanisms still raises debates, seems to be influenced by various psychological factors, including avoidant attachment (avoidance of close emotional relationship) and depressed mood. Sexual desire, different types of motivations for using cybersex, and impulsivity could contribute, to some extent, to this phenomenon. Despite of their preliminary character, current available data lead us to recommend an integrated approach of the treatment of the persons facing these difficulties. | [
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In recent years, the number of smartphone users has exploded worldwide and downloads of applications for these phones have increased significantly. The purpose of this article is to present a review of the literature on the use of smartphone applications to improve sexual health, suggesting how they can be used in sex education, counselling and therapy ; the use of smartphone applications to provide sexual health information, particularly to younger populations, could increase awareness of risky sexual behaviours before first sexual intercourse. This article could help sexologists use smartphone applications to facilitate their work. It is very important that clinicians have specific knowledge of online sexual issues, otherwise they may be vulnerable to stereotypes and judgments. | [
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] |
In this paper, we are presenting a synthetic version of the third updated version of Guidelines for the first-line management by the non-sexologist practitioner of a man with erectile dysfunction (ED). This work applied the methodology recommended by the French High Authority of Health (in-depth documentary search of medical and scientific bibliographic data and review by a group of experts). Among the points to be highlighted since 2010, an important part has been devoted to updating epidemiological data that focus on the strong correlation between ED and vulnerable populations, on the question of the role of the partner's role in triggering or maintaining erectile dysfunction, previously poorly documented, and on the evolution of ED treatments and management algorithms. | [
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Vasculogenic Erectile dysfunction (ED) is one of the main causes of male sexual dysfunction. Several treatments exist to improve the quality of the erection, but the management of the cardiovascular factors is essential to hope a recovery of the erectile function. Recently, several studies have examined the use of low-intensity extracorporeal shock wave therapy (Li-ESWT) to improve vascular and endothelial factors involved in the mechanisms of erection. This article aims to take stock of this potential new therapeutic option. | [
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Relations between sex and genes are well understood in regards to the pathways that control sex differentiation and leading to phenotypic sex. However, the question of the role of genes in gender identity, sexual and affective orientation, or sexual function remains elusive. If the role of steroid hormones on brain development is established, their role on gender identity or sexual orientation is still hypothetical. Concerning sexual function, the attempts to define which genes are potentially involved, have only pointed to genes associated to neurotransmission, but no breakthrough discovery has been made. | [
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Merkel cell carcinoma (MCC) usually arises in sun-exposed areas of older patients and might be more aggressive in the immunocompromised. We performed a retrospective chart review of 40 consecutive MCC patients treated at our institution between the years 2006-2017. Clinical and epidemiologic data were utilized and therapy and survival were analyzed. Compared to Surveillance, Epidemiology, and End Results (SEER) data, our population was entirely Caucasian (100% versus 95%; P=0.11) and male predominant (75% versus 63%; P=0.11). The median age was 76. The patients more often had Tumor-Node-Metastasis (TNM) stage I disease (50% versus 39%; P=0.00003) and a primary tumor size <2cm (57.5% versus 34%; P<0.01). They received more frequently lymph node dissection (70% versus 63%, P=0.002) compared with the SEER findings. We identified a subset of immunocompromised patients (n=10) who presented with more stage III disease (40% versus 33%; P=0.021). Time to death averaged 290.1 days in this subset versus 618.2 days (P<0.001) in immunocompetent patients and their likelihood of death was 5 times higher. As clinical outcomes in MCC patients vary by immunological status, a multidisciplinary tumor-board approach may better optimize individual patient management. | [
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Platelet-rich plasma, which contains numerous growth factors that promote hair growth, is a nonsurgical treatment available for patients with androgenetic alopecia. However, neither the quantity nor the location and depth of platelet-rich plasma placement in the scalp is uniform; in addition, multiple painful injections are required. Vertical uniform channels from the skin surface into the dermis, created by ablative laser fractional photothermolysis, can be used to enhance the cutaneous delivery of medications. This technique - referred to as laser assisted drug delivery - may provide an efficacious means for the administration of platelet-rich plasma to the scalp. It would not only enable the uniform placement of platelet-rich plasma in the dermis (instead of inadvertently in the subcutaneous fat) of androgenetic alopecia patients' scalps, but also eliminate the injection-associated pain. In addition, the topical application of either bimatoprost or minoxidil or both could also be enhanced with laser assisted drug delivery. In conclusion, to potentially maximize the stimulation of hair growth, laser assisted drug delivery of platelet-rich plasma - with or without bimatoprost and/or minoxidil - should be considered in patients with androgenetic alopecia in order to effectively deliver the agents to the dermis where the bulge area of the hair follicles is located. | [
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] |
BACKGROUND: Phototherapy is effective in treating psoriasis and other skin conditions. However, clinic-based phototherapy can be time-consuming, expensive, and inconvenient. Conventional home phototherapy addresses many hurdles, but has other limitations.OBJECTIVE: Assess the treatment efficacy, adherence, and satisfaction of a novel ultraviolet B home phototherapy system.METHODS: Eight patients with stable plaque psoriasis completed a multicenter, prospective, open label, interventional study using a home phototherapy device designed to improve treatment control and adherence. Matched control and study lesions were assessed on each subject. A dosing protocol based on American Academy of Dermatology guidelines for narrowband UVB phototherapy was managed by the phototherapy system. Responsiveness to the treatment was measured using the Psoriasis Severity Index (PSI) at 10 weeks versus control. Patient satisfaction was graded on a five-star Likert scale.RESULTS: At 10 weeks, all patients experienced improvement in the treated lesions, with a mean improvement of 57% in PSI (P<0.0001 compared to baseline and P<0.0002 compared to the control lesions). Patient treatment adherence was 96% and treatment satisfaction was 100% five-star rated. Control lesions did not significantly change in PSI over the 10-week period (P=0.1411).CONCLUSIONS: The home phototherapy system provided a safe and effective means to manage plaque psoriasis. | [
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] |
Non-uremic calciphylaxis is a rare, life-threatening condition characterized clinically by cutaneous necrosis and histologically by calcium deposition in small vessel walls. The etiology of non-uremic calciphylaxis remains the subject of ongoing speculation and debate. Herein we present a patient with calciphylaxis who had normal kidney function and numerous rheumatologic diseases, namely systemic lupus erythematosus (SLE), Sjogren syndrome (SS), and myasthenia gravis (MG). We review the pathophysiology, possible mechanisms, and management for non-uremic calciphylaxis. | [
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] |
Enfortumab vedotin is an antibody-drug conjugate targeting nectin-4 and is being studied in the treatment of various epithelial carcinomas including urothelial carcinoma; early data suggests efficacy and tolerability. Rash has been described as an adverse event associated with treatment with enfortumab vedotin, but has not been characterized to date. We report a patient with metastatic urothelial carcinoma treated with enfortumab vedotin who developed erythematous, scaly papules and plaques on his torso and extremities with corresponding histologic features of vacuolar interface dermatitis and maturation disarray of keratinocytes. He was successfully treated with topical corticosteroids. Cutaneous toxicity appears to be a common adverse reaction in this growing class of antibody-drug conjugates. | [
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Calcific uremic arteriolopathy (CUA) or calciphylaxis is a syndrome characterized by calcification of vessels located in the dermis and adipose tissue. It commonly occurs in patients with diabetes mellitus, hypertension, and end-stage renal disease. Clinical presentation generally begins with severe pain, followed by the presence of liveloid or purpuric plaques. Later the formation necrotic ulcers occur. This condition is associated with a poor prognosis, with a high rate of mortality within months of the diagnosis. Penile involvement is an uncommon but severe manifestation. We present an 81-year-old man with a history of diabetes mellitus, hypertension, and end-stage renal disease with a one-month evolution of painful necrotic ulcers on his glans penis. He was diagnosed with CUA. Owing to infection complicated by sepsis; penectomy was performed. Unfortunately, the patient died of myocardial infarction during his hospitalization. | [
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] |
Angiolipoma, a subtype of lipoma, is a benign adypocytic soft tissue tumor composed of mature adipose tissue and small vascular proliferations. This entity makes up 5-17% of all lipomas. The diagnosis is made by clinical and pathological examination, ultrasonography, and/or magnetic resonance imaging (MRI). It is generally an encapsulated tumor (noninfiltrative), but rarely has an infiltrative form. Angiolipoma mostly occurs on the trunk and extremities with male predominance. The forearm is the most frequent location for angiolipomas. It is very rarely seen on the fingers. Herein, we report a patient with solitary noninfiltrating angiolipoma on a finger. The patient was treated with surgical excision and no recurrence has been noted over one year of observation. | [
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A blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a cutaneous lymphoma derived from a plasmacytoid dendritic precursor cell that exhibits aggressive clinical behavior. Herein, we report a 46-year-old woman with a complaint of a painless nodule on the back, associated with pruritus. The nodule grew and new growths appeared over six months of evolution. The histopathological examination of one of the left upper limb lesions showed a dense lymphoid cell infiltrate with atypia in the superficial and deep dermis. Immunohistochemistry showed positivity for CD45, S-100 protein, CD123, and TCL 1. About two months after the initial evaluation, the patient was admitted to the Emergency Hospital of Marituba-PA with dyspnea. She progressed to cardiorespiratory arrest and death within 12 hours of admission. There is still no consensus for the treatment of BPDCN. Intensive therapy for acute leukemia can be useful, but allogeneic bone marrow transplantation has a greater chance of long-term survival. | [
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Mycobacterium marinum is a nontuberculous mycobacteria with worldwide distribution that lives in fresh or salt water and is responsible for infections in fish, and sometimes in humans. Human disease consists mainly of cutaneous nodules, but deep structure involvement may also occur. Diagnosis of M. marinum infection remains a challenge, with a considerable time delay between onset of symptoms and diagnosis. We present a 33-year-old man with no immunosuppressive history who was seen in our department with skin nodules over his hand and forearm, distributed in a sporotrichoid pattern. His hobbies included maintaining an aquarium of tropical fish. Histological examination of the patient's skin biopsy was compatible with the diagnosis of mycobacterial infection, and the Ziehl-Neelsen staining revealed acid-fast bacilli. Molecular techniques confirmed the suspicion of M. marinum infection. A necropsy was performed on one of the patient's fish, more specifically, a Poecilia reticulata, and resulted in identification of M. marinum from its gut. The patient was treated with clarithromycin, ethambutol, and rifampicin for 9 months, with clearance of infection. | [
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] |
Clinicians have a tendency to dismiss patients with psychiatric illness like skin picking disorder without assessing completely for organic disease. Patients with psychocutaneous disease have the potential to develop true dermatopathology and should always be examined thoroughly. We describe a case of skin picking disorder with underlying pilomatricoma. The patient met criteria for skin picking disorder and had been prescribed numerous topical treatments without efficacy by countless physicians over 18 years. In addition, a pilomatricoma was discovered within a self-inflicted ulcer. Pilomatricomas can rarely result from trauma and develop ossification, both of which were true of this lesion. The prevalence of skin picking disorder proves more pervasive than previously realized and it has only recently been recognized by the DSM-5 as an independent diagnosis. Therefore, it is necessary to clarify the diagnosis as well as remind clinicians not to discount underlying dermatologic disease. In addition to the risk of bleeding and infection, these patients are at risk for masking neoplasms, which should be removed. Our case emphasizes the need for thorough examination of patients with psychocutaneous disease and further work-up when necessary to prevent permanent disfigurement. | [
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Condyloma lata, a cutaneous manifestation of secondary syphilis, usually appear as verrucous papules and plaques in the anogenital area. Involvement of the umbilicus is very uncommon. Thus, awareness of this presentation, along with appropriate history, physical exam, and laboratory testing may aid clinicians in prompt and accurate diagnosis. We describe a patient with an unusual presentation of condyloma lata on the umbilicus. | [
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] |
Seborrheic keratosis is a benign condition that can mimic many different non-melanoma and melanoma neoplasms. There have been several case reports of underlying squamous cell carcinomas or intraepidermal carcinomas appearing within lesions that look analogous to seborrheic keratoses. We present a patient with a verrucous melanoma that could be mistaken for a benign skin tumor like an inflamed seborrheic keratosis. In our patient's case, her verrucous plaque was initially clinically suggestive of a benign seborrheic keratosis. However, given the patient's complaint of pain associated with the lesion, a biopsy was performed and revealed a verrucous-keratotic malignant melanoma, which was subsequently removed through surgical excision. It is important to remain vigilant of this diagnosis, as treatment for inflamed seborrheic keratosis often includes a trial of cryotherapy, which potentially could lead to a delayed diagnosis of an underlying malignant lesion. | [
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Eccrine hidrocystoma is a benign cystic tumor. Such benign cystic lesions may be a cosmetic concern, or when large, can cause eyelid malpositions. We report a patient with a peri-punctal hidrocystoma of the eyelid. | [
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] |
Pretibial myxedema or thyroid dermopathy constitutes dermal deposition of mucin, primarily hyaluronic acid and chondroitin sulfate. It is a manifestation of autoimmune thyroiditis, seen more in Graves disease than in Hashimoto thyroiditis. The time delay from treatment of hyperthyroidism to appearance of localized myxedema varies from one month to 16 years (mean 5.13 years). Despite a variety of therapeutic options, failure and relapse rates are high. Therapeutic options reported in the literature include compression, topical and intralesional corticosteroids, oral pentoxifylline, octreotide, rituximab, plasmapheresis, and high-dose intravenous immunoglobulin. We share our experience in two patients who were treated with electrosurgical debulking of selected longstanding myxedematous lesions, with one positive result and one negative result. | [
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Acrodermatitis continua of Hallopeau, first described in 1890, is an uncommon variant of pustular psoriasis. It presents as a sterile pustular eruption of the tips of fingers and toes. The condition has a chronic, relapsing course and is often resistant to many anti-psoriatic therapies. In the following case, we present our experience of etanercept use in a 61-year-old man. Although initial therapy with high-dose etanercept achieved a rapid, sustained response and remission, the lesions relapsed a few months into a lower, maintenance dosage. This result prompted the use a second biotherapeutic agent ustekinumab, which resulted in complete remission, but required a higher dosage than recommended with reduced dosing intervals. | [
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] |
Tuning ice recrystallization (IR) has attracted tremendous interest in fundamental research and a variety of practical applications, including food and pharmaceutical engineering, fabrication of anti-icing coating and porous materials, and cryopreservation of biological cells and tissues. Although great efforts have been devoted to modulation of IR for better microstructure control of various materials, it still remains a challenge, especially in cryopreservation, where insufficient suppression of IR during warming is fatal to the cells. Herein, we report an all-in-one platform, combining the external physical fields and the functional materials for both active and passive suppression of IR, where the photo- and magnetothermal dual-modal heating of GO-Fe3O4 nanocomposites (NCs) can be used to suppress IR with both enhanced global warming and microscale thermal disturbance. Moreover, the materials alginate hydrogels and GO-Fe3O4 NCs can act as IR inhibitors for further suppression of the IR effect. As a typical application, we show that this GO-Fe3O4 nanocomposite-alginate hydrogel platform can successfully enable low-cryoprotectant, high-quality vitrification of stem cell-laden hydrogels. We believe that the versatile ice recrystallization inhibition platform will have a profound influence on cryopreservation and tremendously facilitate stem cell-based medicine to meet its ever-increasing demand in clinical settings. | [
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Molecular gels formed by the self-assembly of low-molecular-weight gelators have received increasing interest because of their potential applications in drug delivery. In particular, the ability of peptides and amino acids to spontaneously self-assemble into three-dimensional fibrous network has been exploited in the development of hydrogels. In this context, we have investigated the capacity of binary mixtures of aromatic amino acid derivatives to form hydrogels. Carbon nanomaterials, namely oxidized carbon nanotubes or graphene oxide, were incorporated in the two most stable hydrogels, formed by Fmoc-Tyr-OH/Fmoc-Tyr(Bzl)-OH and Fmoc-Phe-OH/Fmoc-Tyr(Bzl)-OH, respectively. The structural and physical properties of these gels were assessed using microscopic techniques and rheology. Circular dichroism and molecular dynamics simulations demonstrated that the hydrogel formation was mainly driven by aromatic interactions. Finally, a model hydrophilic drug (l-ascorbic acid) was loaded into the hybrid hydrogels at a high concentration. Under near-infrared light irradiation, a high amount of drug was released triggered by the heat generated by the carbon nanomaterials, thus offering interesting perspectives for controlled drug delivery. | [
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As novel alternatives to perfluorooctanoic acid (PFOA), perfluoropolyether carboxylic acids (multiether PFECAs, CF3(OCF2) nCOO-, n = 2-4) have been detected in various environmental matrices; however, public information regarding their toxicities remains unavailable. To compare the hepatotoxicity of multiether PFECAs (e.g., PFO2HxA, PFO3OA, and PFO4DA) with PFOA, male mice were exposed to 0.4, 2, or 10 mg/kg/d of each chemical for 28 d, respectively. Results demonstrated that PFO2HxA and PFO3OA exposure did not induce marked increases in relative liver weight; whereas 2 and 10 mg/kg/d of PFO4DA significantly increased relative liver weight. Furthermore, PFO2HxA and PFO3OA demonstrated almost no accumulation in the liver or serum; whereas PFO4DA was accumulated but with weaker potential than PFOA. Exposure to 10 mg/kg/d of PFO4DA led to 198 differentially expressed liver genes (56 down-regulated, 142 up-regulated), with bioinformatics analysis highlighting the urea cycle disorder. Like PFOA, 10 mg/kg/d of PFO4DA decreased the urea cycle-related enzyme protein levels (e.g., carbamoyl phosphate synthetase 1) and serum ammonia content in a dose-dependent manner. Both PFOA and PFO4DA treatment (highest concentration) caused a decrease in glutamate content and increase in both glutamine synthetase activity and aquaporin protein levels in the brain. Thus, we concluded that PFO4DA caused hepatotoxicity, as indicated by hepatomegaly and karyolysis, though to a lesser degree than PFOA, and induced urea cycle disorder, which may contribute to the observed toxic effects. | [
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] |
This study investigated the methodology and utility of dendrochemistry in the assessment of spatial and temporal concentrations of gaseous elemental mercury. Tree cores from the Pinus species in California and Nevada, U.S.A. were collected from previously sampled areas to test the stability of tree ring concentrations over time. Cores were collected from 2 new locations to assess spatial variability among trees within and between stands located at two elevations in the same watershed. Results indicated that using 2 to 3 cores from ?10 or more trees provided the best framework for understanding tree ring concentrations within a population of trees located in uncontaminated areas. At the least 2 sides of a tree should be cored to account for radially asymmetric variations associated with growing conditions or injury. An agreement of concentrations and trends measured in trees cored with previous research indicated that tree rings are suitable proxies for historical air mercury concentrations and that mercury concentrations have increased since the Industrial Revolution. Data collected demonstrate that tree rings record regional gradients in GEM concentrations. In addition, temporal consistency may vary within a geographic location due to differing biotic and abiotic factors influencing ring growth since trees are active samplers of atmospheric Hg. | [
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Subsets and Splits