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Background: Medical education, residency training, and the structure of child neurology residency training programs are evolving. We sought to evaluate how training program selection priorities of child neurology residency applicants have changed over time.Methods: An electronic survey was sent to child neurology residents and practicing child neurologists via the Professors of Child Neurology distribution list in the summer of 2018. It was requested that the survey be disseminated to current trainees and alumni of the programs. The survey consisted of seven questions assessing basic demographics and a list of factors applicants consider when choosing a residency.Results: There were 284 responses with a higher representation of individuals matriculating into residency in the last decade. More recent medical school graduates had a lower probability of considering curriculum as an important factor for residency selection (odds ratio [OR], 0.746; 95% confidence interval [95% CI], 0.568 to 0.98; P = 0.035) and higher priority placed on interaction with current residents over the course of the interview day (OR, 2.207; 95% CI, 1.486 to 3.278; P < 0.0001), sense of resident happiness and well-being (OR, 2.176; 95% CI, 1.494 to 3.169; P < 0.0001), and perception of city or geography of the residency program (OR, 1.710; 95% CI, 1.272 to 2.298; P < 0.001).Conclusions: Over time, child neurology residency applicants are putting more emphasis on quality of life factors over curriculum. To accommodate these changes, child neurology residency programs should prioritize interactions with residents during the interview process and resident wellness initiatives throughout residency training. [ABSTRACT FROM AUTHOR]

Here, we demonstrate that the upregulation of catalase is required to compensate for the loss of nicotinamide nucleotide transhydrogenase (NNT) to maintain hydrogen peroxide (H 2 O 2) steady-state levels in C57BL/6J liver mitochondria. Our investigations using the closely related mouse strains C57BL/6NJ (6NJ; +NNT) and C57BL/6J (6J; -NNT) revealed that NNT is required for the provision of NADPH and that the upregulation of isocitrate dehydrogenase-2 (IDH2) activity is not enough to compensate for the absence of NNT, which is consistent with previous observations. Intriguingly, despite the absence of NNT, 6J mitochondria had rates of H 2 O 2 production (58.56 ± 3.79 pmol mg−1 min−1) that were similar to samples collected from 6NJ mice (72.75 ± 14.26 pmol mg−1 min−1) when pyruvate served as the substrate. However, 6NJ mitochondria energized with succinate produced significantly less H 2 O 2 (59.95 ± 2.13 pmol mg−1 min−1) when compared to samples from 6J mice (116.39 ± 20.74 pmol mg−1 min−1), an effect that was attributed to the presence of NNT. Further investigations into the H 2 O 2 eliminating capacities of these mitochondria led to the novel observation that 6J mitochondria compensate for the loss of NNT by upregulating catalase. Indeed, 6NJ and 6J mitochondria energized with pyruvate or succinate displayed similar rates for H 2 O 2 elimination, quenching ~84% and ~86% of the H 2 O 2 , respectively, in the surrounding medium within 30 s. However, inclusion of palmitoyl-CoA, an NNT inhibitor, significantly limited H 2 O 2 degradation by 6NJ mitochondria only (~55% of H 2 O 2 eliminated in 30 s). Liver mitochondria from 6J mice treated with palmitoyl-CoA still cleared ~80% of the H 2 O 2 from the surrounding environment. Inhibition of catalase with triazole compromised the capacity of 6J mitochondria to maintain H 2 O 2 steady-state levels. By contrast, disabling NADPH-dependent antioxidant systems had a limited effect on the H 2 O 2 clearing capacity of 6J mitochondria. Liver mitochondria collected from 6NJ mice, on the other hand, were more reliant on the GSH and TRX systems to clear exogenously added H 2 O 2. However, catalase still played an integral in eliminating H 2 O 2 in 6NJ liver mitochondria. Immunoblot analyses demonstrated that catalase protein levels were ~7.7-fold higher in 6J mitochondria. Collectively, our findings demonstrate for the first time that 6J liver mitochondria compensate for the loss of NNT by increasing catalase levels for the maintenance of H 2 O 2 steady-state levels. In general, our observations reveal that catalase is an integral arm of the antioxidant response in liver mitochondria. Image 1 • NNT is integral for maintaining H 2 O 2 steady-state levels. • Loss of NNT increases mitochondrial catalase levels. • Compensatory increase in catalase preserves H 2 O 2 homeostasis. • Loss of NNT also increases IDH2 and proton leaks. [ABSTRACT FROM AUTHOR]

Climate change is recognised as a significant public health issue that will impact on food security. One of the major contributors to global warming is the livestock industry, and, relative to plant-based agriculture, meat production has a much higher environmental impact in relation to freshwater use, amount of land required, and waste products generated. Promoting increased consumption of plant-based foods is a recommended strategy to reduce human impact on the environment and is also now recognised as a potential strategy to reduce the high rates of some chronic diseases such as cardiovascular disease and certain cancers. Currently there is a scant evidence base for policies and programs aiming to increase consumption of plant-based diets and little research on the necessary conditions for that change to occur and the processes involved in such a change. This paper reviews some of the environmental and health consequences of current dietary practices, reviews literature on the determinants of consuming a plant-based diet, and provides recommendations for further research in this area. [ABSTRACT FROM AUTHOR]

Abstract: Four common classification methods are described, Euclidean Distance to Centroids (EDC), Linear Discriminant Analysis (LDA), Quadratic Discriminant Analysis (QDA) and Support Vector Machines (SVM). In many applications of chemometrics e.g. in medicine and biology it is common for there to be unequal sample sizes in different groups. When class sizes are unequal the performance of some of these methods may be biased according to class size. This paper describes approaches for incorporating prior probabilities of class membership using Bayesian approaches to three of the methods LDA, QDA and SVM, either assuming equal probability or assuming that the relative sample sizes relate to the relative probabilities. EDC is used as a benchmark to determine model stabilities. The methods are illustrated by four simulated datasets of different structures and one real dataset consisting of the gas chromatographic profile of mouse urine comparing controls to those on a diet. [Copyright &y& Elsevier]

Abstract: Five methods for discrimination are described, namely Euclidean Distance to centroids (EDC), Linear Discriminant Analysis (LDA) (based on the Mahalanobis distance and pooled variance covariance matrix), Quadratic Discriminant Analysis (QDA) (based on the Mahalanobis distance and individual class variance covariance matrix — non-Bayesian form), Learning Vector Quantization (LVQ) and Support Vector Machines (SVMs) (using soft boundaries and Radial Basis Functions), and illustrated graphically as boundary methods. The performance of each method was determined using four synthetic datasets each consisting of 200 samples half belonging to one of two classes, and a further two synthetic datasets containing 400 samples, again equally split between the two classes. In datasets 1 to 3, five variables were distributed multinormally, in dataset 1 the classes are distributed roughly circularly but with a significant degree of overlap, in dataset 2, the distribution is in elongated hyperellipsoids with small overlap, and in dataset 3 there is a region of complete overlap between classes. In dataset 4 two variables are distributed in a crescent shape. In datasets 5 and 6, 100 variables were generated from multinormal populations, some of which were potential discriminators, however a large proportion of the variables were designed to be uninformative. The methods were optimised using a training set and their performance evaluated using a test set: this was repeated 100 times for different test and training set splits. The average % correctly classified was computed for each class and model, as well as the model stability for each sample (the proportion of times the sample is classified into the same group over all 100 iterations). The conclusions are that the performance of the classifiers depends very much on the distribution of data. Approaches such as LVQ and SVMs that try to determine complex boundaries perform best when the data is not normally distributed such as in dataset 4, but can be prone to overfitting otherwise. QDA tends to perform best on multinormal data although it can be influenced by non-discriminative variables which show a difference in variance. It is recommended to look at the data structure prior to model building to determine the optimal type of model. [Copyright &y& Elsevier]

Abstract: Pattern recognition studies are performed on the gas chromatography mass spectrometry of extracts of human sweat of 182 subjects sampled 5 times (over 5 fortnights), in an attempt to determine whether it is possible to classify samples into those arising from males and females. All methods were applied to peak tables of square root normalised GC-MS peak areas. Potential markers were identified using both a univariate (t-statistic) and multivariate (Partial Least Squares Discriminant Analysis: PLS-DA) method, on each fortnight separately, selecting those peaks that have high ranks each fortnight. Classification was performed using PLS-DA, selecting the model using 100 repetitions for each fortnight dividing the data into test and training sets randomly, and using the bootstrap to find the number of significant components for each of the 100 models. Contingency tables can be drawn up for the number of misclassified samples, using three error criteria, namely autoprediction, bootstrap and test set. The decision threshold for which sample is assigned to a group can be adjusted and Receiver Operator Characteristic curves were used to visualise the influence on changing this threshold. It is shown that by using the entire set of 910 measurements there is a closer correspondence between autoprediction and test set error rates than for 182 measurements where there is less agreement, suggesting that sample size has a key role. A general strategy for studying large metabolomics datasets is proposed. [Copyright &y& Elsevier]

Abstract: Tandem mass spectrometry is used to monitor the contamination of banknotes by cocaine. By introducing a series of banknotes into an instrument a distribution of contamination can be obtained. The distribution of samples arising from defendants where the banknotes have been in close proximity to cocaine should differ from the distribution from the general background population. Peak picking and integration is used to produce a series of intensity readings for a batch of banknotes. By visually inspecting these distribution, and applying a variety of chemometric methods (principal components analysis, cluster analysis and class modelling via Mahalanobis distance) it is possible to discriminate effectively between the two classes of distribution (7157 background notes and 4826 case notes alleged to be from drug dealers). By calculating the Mahalonobis distance over 100 bootstrap iterations, background samples were correctly classified 96.48% of the time, while case samples were correctly classified 89.37% of the time. [Copyright &y& Elsevier]

Cohesin's association with and translocation along chromosomal DNAs depend on an ATP hydrolysis cycle driving the association and subsequent release of DNA. This involves DNA being 'clamped' by Scc2 and ATP-dependent engagement of cohesin's Smc1 and Smc3 head domains. Scc2's replacement by Pds5 abrogates cohesin's ATPase and has an important role in halting DNA loop extrusion. The ATPase domains of all SMC proteins are separated from their hinge dimerisation domains by 50-nm-long coiled coils, which have been observed to zip up along their entire length and fold around an elbow, thereby greatly shortening the distance between hinges and ATPase heads. Whether folding exists in vivo or has any physiological importance is not known. We present here a cryo-EM structure of the apo form of cohesin that reveals the structure of folded and zipped-up coils in unprecedented detail and shows that Scc2 can associate with Smc1's ATPase head even when it is fully disengaged from that of Smc3. Using cysteine-specific crosslinking, we show that cohesin's coiled coils are frequently folded in vivo, including when cohesin holds sister chromatids together. Moreover, we describe a mutation (SMC1D588Y) within Smc1's hinge that alters how Scc2 and Pds5 interact with Smc1's hinge and that enables Scc2 to support loading in the absence of its normal partner Scc4. The mutant phenotype of loading without Scc4 is only explicable if loading depends on an association between Scc2/4 and cohesin's hinge, which in turn requires coiled coil folding. [ABSTRACT FROM AUTHOR]

Climate change is recognised as a significant public health issue that will impact on food security. One of the major contributors to global warming is the livestock industry, and, relative to plant-based agriculture, meat production has a much higher environmental impact in relation to freshwater use, amount of land required, and waste products generated. Promoting increased consumption of plant-based foods is a recommended strategy to reduce human impact on the environment and is also now recognised as a potential strategy to reduce the high rates of some chronic diseases such as cardiovascular disease and certain cancers. Currently there is a scant evidence base for policies and programs aiming to increase consumption of plant-based diets and little research on the necessary conditions for that change to occur and the processes involved in such a change. This paper reviews some of the environmental and health consequences of current dietary practices, reviews literature on the determinants of consuming a plant-based diet, and provides recommendations for further research in this area. [ABSTRACT FROM AUTHOR]

The article reports that according to scientists in Italy amino acids that initiated life on earth could have traveled on interstellar silica dust particles from deep space to the Earth.

The article presents information on the mapping of drugs by magnetic resonance imaging for the testing of pharmaceuticals that are used for the treatment of brain diseases.

The article offers information on separation of complex chemical mixtures to recover high value products and catalytic nanoparticles using light as the oil and water phases carrying a light-sensitive surfactants get separated from the emulsions, when an ultraviolet (UV) light is passed through it.

The presence of multiple bleeding symptoms and/or severe bleeding symptom(s) contribute to a higher score and therefore a greater chance of a bleeding disorder diagnosis. There is bleeding at a critical site (e.g., ICH, retinal haemorrhage, gastrointestinal haemorrhage, intraspinal haemorrhage, haemarthrosis) with no correlating history of trauma or other explanation that adequately accounts for the bleeding. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. A standardised bleeding assessment tool, e.g., the International Society for Haemostasis and Thrombosis Bleeding Assessment Tool (ISTH-BAT), can be used to quantitate bleeding symptoms in order to generate a bleeding score. [Extracted from the article]

Environmental legislation such as the American Innovation and Manufacturing Act will phase out today's generation of high-global warming hydrofluorocarbon refrigerants over the next two decades. Energy-efficient technologies are needed to separate these often azeotropic and complex mixtures. Membrane technology and extractive distillation with ionic liquids as entrainers have been individually developed for the separation of azeotropic refrigerant mixtures. This study provides details for the separation of R-410A through combining the benefits of glassy, amorphous polymers with ionic liquids to form ionic liquid polymer membranes. Two different classes of ionic liquid polymer membranes are considered: polyvinyl acetate composite membranes with 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, 1-hexyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate, and 1-hexyl-3-methylimidazolium chloride, and Hyflon AD 60 with 1-ethyl-3-methylimidazolium bis(pentafluoroethylsulfonyl)imide. The membranes are characterized with FTIR, helium pycnometry, differential scanning calorimetry, and a high-pressure view-cell to characterize the effect of ionic liquid on polymer properties. The Hyflon AD 60 composite membranes were evaluated for the separation of R-410A through pure-gas permeability, selectivity, solubility, and diffusivity measurements, which show exceptional selectivity for separation of R-410A. Results provide insights on the effect of ionic liquid on the separation of R-410A and indicate that improved separation performance of glassy polymers can be achieved with the addition of ionic liquid. [Display omitted] • Created stable fluorinated ionic liquid polymer membranes for the separation of R-410A • Fluorinated ionic liquid polymer membranes have a selectivity >150 for R-410A separation. • Solubility switches to less condensable HFC-32 with introduction of ionic liquid. [ABSTRACT FROM AUTHOR]

Cohesin's structural maintenance of chromosome 1 (Smc1) and Smc3 are rod-shaped proteins with 50-nm long intra-molecular coiled-coil arms with a heterodimerization domain at one end and an ABC-like nucleotide-binding domain (NBD) at the other. Heterodimerization creates V-shaped molecules with a hinge at their centre. Inter-connection of NBDs by Scc1 creates a tripartite ring within which, it is proposed, sister DNAs are entrapped. To investigate whether cohesin's hinge functions as a possible DNA entry gate, we solved the crystal structure of the hinge from Mus musculus, which like its bacterial counterpart is characterized by a pseudo symmetric heterodimeric torus containing a small channel that is positively charged. Mutations in yeast Smc1 and Smc3 that together neutralize the channel's charge have little effect on dimerization or association with chromosomes, but are nevertheless lethal. Our finding that neutralization reduces acetylation of Smc3, which normally occurs during replication and is essential for cohesion, suggests that the positively charged channel is involved in a major conformational change during S phase. [ABSTRACT FROM AUTHOR]

Omega (n)-3 polyunsaturated fatty acids (PUFA) are known to regulate lipid metabolism and inflammation; however, the regulation of maternal lipid metabolism and cytokines profile by n-3 PUFA during different gestation stages, and its impact on fetal sustainability is not known. We investigated the effects of maternal diet varying in n-3 PUFA prior to, and during gestation, on maternal metabolic profile, placental inflammatory cytokines, and fetal outcomes. Female C57BL/6 mice were fed either a high, low or very low (9, 3 or 1% w/w n-3 PUFA) diet, containing n-6:n-3 PUFA of 5:1, 20:1 and 40:1, respectively for two weeks before mating, and throughout pregnancy. Animals were sacrificed prior to mating (NP), and during pregnancy at gestation days 6.5, 12.5 and 18.5. Maternal metabolic profile, placental cytokines and fetal outcomes were determined. Our results show for the first time that a maternal diet high in n-3 PUFA prevented dyslipidemia in NP mice, and maintained the expected lipid profile during pregnancy. However, females fed the very low n-3 PUFA diet became hyperlipidemic prior to pregnancy, and carried this profile into pregnancy. Maternal diet high in n-3 PUFA maintained maternal plasma progesterone and placental pro-inflammatory cytokines profile, and sustained fetal numbers throughout pregnancy, while females fed the low and very-low n-3 PUFA diet had fewer fetuses. Our findings demonstrate the importance of maternal diet before, and during pregnancy, to maintain maternal metabolic profile and fetus sustainability. These findings are important when designing dietary strategies to optimize maternal metabolism during pregnancy for successful pregnancy outcome. [ABSTRACT FROM AUTHOR]

The majority of works in metabolomics employ approaches based on principal components analysis (PCA) and partial least-squares, primarily to determine whether samples fall within large groups. However, analytical chemists rarely tackle the problem of individual finger-printing, and in order to do this effectively, it is necessary to study a large number of small groups rather than a small number of large groups and different approaches are required, as described in this paper. Furthermore, many metabolomic studies on mammals and humans involve analyzing compounds (or peaks) that are present in only a certain portion of samples, and conventional approaches of PCA do not cope well with sparse matrices where there may be many Os. There is, however, a large number of qualitative similarity measures available for this purpose that can be exploited via principal coordinates analysis (PCO). It can be shown that PCA scores are a specific case of PCO scores, using a quantitative similarity measure. A large-scale study of human sweat consisting of nearly 1000 gas chromatography/mass spectrometry analyses from the sweat of an isolated population of 200 individuals in Carinthia (Southern Austria) sampled once per fortnight over 10 weeks was employed in this study and grouped into families. The first step was to produce a peak table requiring peak detection, alignment, and integration. Peaks were reduced from 5080 to 373 that occurred in at least 1 individual over 4 out of 5 fortnights. Both qualitative (presence/absence) and quantitative (equivalent to PCA) similarity measures can be computed. PCO and the Kolomorogov-Smirnoff (KS) rank test are applied to these similarity matrices. It is shown that for this data set there is a reproducible individual fingerprint, which is best represented using the qualitative similarity measure as assessed both by the Hotelling t2 statistic as applied to PCO scores and the probabilities associated with the KS rank test. [ABSTRACT FROM AUTHOR]

Understanding athletes’ attitudes to doping continues to be of interest for its potential to contribute to an international anti-doping system. However, little is known about the relationship between elite athletes’ attitudes to drug use and potential explanatory factors, including achievement goals and the motivational climate. In addition, despite specific World Anti-Doping Agency Code relating to team sport athletes, little is known about whether sport type (team or individual) is a risk or protective factor in relation to doping. Elite athletes from Scotland (N = 177) completed a survey examining attitudes to performance-enhancing drug (PED) use, achievement goal orientations and perceived motivational climate. Athletes were generally against doping for performance enhancement. Hierarchical regression analysis revealed that task and ego goals and mastery motivational climate were predictors of attitudes to PED use (F(4, 171) = 15.81,P < .01). Compared with individual athletes, team athletes were significantly lower in attitude to PED use and ego orientation scores and significantly higher in perceptions of a mastery motivational climate (Wilks’ lambda = .76,F = 10.89 (5, 170),P < .01). The study provides insight into how individual and situational factors may act as protective and risk factors in doping in sport. [ABSTRACT FROM AUTHOR]

Understanding athletes’ attitudes to doping continues to be of interest for its potential to contribute to an international anti-doping system. However, little is known about the relationship between elite athletes’ attitudes to drug use and potential explanatory factors, including achievement goals and the motivational climate. In addition, despite specific World Anti-Doping Agency Code relating to team sport athletes, little is known about whether sport type (team or individual) is a risk or protective factor in relation to doping. Elite athletes from Scotland (N = 177) completed a survey examining attitudes to performance-enhancing drug (PED) use, achievement goal orientations and perceived motivational climate. Athletes were generally against doping for performance enhancement. Hierarchical regression analysis revealed that task and ego goals and mastery motivational climate were predictors of attitudes to PED use (F(4, 171) = 15.81,P < .01). Compared with individual athletes, team athletes were significantly lower in attitude to PED use and ego orientation scores and significantly higher in perceptions of a mastery motivational climate (Wilks’ lambda = .76,F = 10.89 (5, 170),P < .01). The study provides insight into how individual and situational factors may act as protective and risk factors in doping in sport. [ABSTRACT FROM AUTHOR]

Human saliva not only helps control oral health (with anti-microbial proteins), but it may also play a role in chemical communication. As is the case with other mammalian species, human saliva contains peptides, proteins, and numerous volatile organic compounds (VOCs). A high-throughput analytical method is described for profiling a large number of saliva samples to screen the profiles of VOCs. Saliva samples were collected in a non-stimulated fashion. The method utilized static stir bar extraction followed by gas chromatography-mass spectrometry (GC-MS). The method provided excellent reproducibility for a wide range of salivary compounds, including alcohols, aldehydes, ketones, carboxylic acids, esters, amines, amides, lactones, and hydrocarbons. Furthermore, substantial overlap of salivary VOCs and the previously reported skin VOCs in the same subject group was found in this study by using pattern recognition analyses. Sensitivity, precision, and reproducibility of the method suggest that this technique has potential in physiological, metabolomic, pharmacokinetic, forensic, and toxicological studies of small organic compounds where a large number of human saliva samples are involved. [ABSTRACT FROM AUTHOR]

Summary: Background: The cohesin complex that mediates sister chromatid cohesion contains three core subunits: Smc1, Smc3, and Scc1. Heterotypic interactions between Smc1 and Smc3 dimerization domains create stable V-shaped Smc1/Smc3 heterodimers with a hinge at the center and nucleotide-binding domains (NBDs) at the ends of each arm. Interconnection of each NBD through their association with the N- and C-terminal domains of Scc1 creates a tripartite ring, within which sister DNAs are thought to be entrapped (the ring model). Crystal structures show that the Smc1/Smc3 hinge has a toroidal shape, with independent “north” and “south” interaction surfaces on an axis of pseudosymmetry. The ring model predicts that sister chromatid cohesion would be lost by transient hinge opening. Results: We find that mutations within either interface weaken heterodimerization of isolated half hinges in vitro but do not greatly compromise formation of cohesin rings in vivo. They do, however, reduce the residence time of cohesin on chromosomes and cause lethal defects in sister chromatid cohesion. This demonstrates that mere formation of rings is insufficient for cohesin function. Stable cohesion requires cohesin rings that cannot easily open. Conclusions: Either the north or south hinge interaction surface is sufficient for the assembly of V-shaped Smc1/Smc3 heterodimers in vivo. Any tendency of Smc proteins with weakened hinges to dissociate will be suppressed by interconnection of their NBDs by Scc1. We suggest that transient hinge dissociation caused by the mutations described here is incompatible with stable sister chromatid cohesion because it permits chromatin fibers to escape from cohesin rings. [Copyright &y& Elsevier]