Evaluation of the effect of reactive sulfide on the acute toxicity of silver (I) to Daphnia magna. Part 1: description of the chemical system.
Experiments were designed to assess the potential protective effect of the presence of sulfide against the acute (48-h) toxicity of silver(I) to Daphnia magna. Tests were conducted in borosilicate glass beakers (250 ml) in moderately hard synthetic water. Toxicity solutions were replaced after 24 h by static renewal method. This paper describes the chemical system, and the acute toxicity results are presented in a companion paper. Sulfide was below detection limit (<5 nM) in controls with no sulfide added. Sulfide, added as zinc sulfide clusters at approximately 35- or approximately 350-nM concentration, dropped in concentration to approximately 25 and 250 nM, respectively, over the 24-h period of measurements. Silver also decreased in concentration during the experiment (up to 59%), and the rate of loss was greater in the absence of sulfide compared with the presence of sulfide. A filtration experiment indicated a 1:1 binding ratio of silver to sulfide and a conditional stability constant for the Ag(I)-zinc sulfide complex of log K' = 8.9. The losses of sulfide and silver during the experiments highlighted the need for regular monitoring of the important chemical components of the system, even during short (48-h) toxicity tests.


Effective critical electric field for runaway-electron generation.
In this Letter we investigate factors that influence the effective critical electric field for runaway-electron generation in plasmas. We present numerical solutions of the kinetic equation and discuss the implications for the threshold electric field. We show that the effective electric field necessary for significant runaway-electron formation often is higher than previously calculated due to both (1) extremely strong dependence of primary generation on temperature and (2) synchrotron radiation losses. We also address the effective critical field in the context of a transition from runaway growth to decay. We find agreement with recent experiments, but show that the observation of an elevated effective critical field can mainly be attributed to changes in the momentum-space distribution of runaways, and only to a lesser extent to a de facto change in the critical field.


First experience with single-source, dual-energy CCTA for monochromatic stent imaging.
Single-source, dual-energy coronary computed tomography angiography (CCTA) with monochromatic image reconstruction allows significant noise reduction. The aim of the study was to evaluate the impact of monochromatic CCTA image reconstruction on coronary stent imaging, as the latter is known to be affected by artefacts from highly attenuating strut material resulting in artificial luminal narrowing. Twenty-one patients with 62 stents underwent invasive coronary angiography and single-source, dual-energy CCTA after stent implantation. Standard polychromatic images as well as eight monochromatic series (50, 60, 70, 80, 90, 100, 120, and 140 keV) were reconstructed for each CCTA. Signal and noise were measured within the stent lumen and in the aortic root. Mean in-stent luminal diameter was assessed in all CCTA reconstructions and compared with quantitative invasive coronary angiography (QCA). Luminal attenuation was higher in the stent than in the aortic root throughout all monochromatic reconstructions (P < 0.001). An increase in monochromatic energy was associated with a decrease in luminal attenuation values (P < 0.001). The mean in-stent luminal diameter underestimation by monochromatic CCTA compared with QCA was 90% at low monochromatic energy (50 keV) and improved to 37% at high monochromatic (140 keV) reconstruction while stent diameter was underestimated by 39% with standard CCTA. Monochromatic CCTA can be used reliably in patients with coronary stents. However, reconstructions with energies below 80 keV are not recommended as the blooming artefacts are most pronounced at such low energies, resulting in up to 90% stent diameter underestimation.


Economic effects of subclinical infectious bursal disease on broiler production.
A survey of the infectious bursal disease (IBD) status of 85 clinically normal broiler flocks was carried out. Flocks were grouped into three categories: flocks without IBD lesions (category A), flocks with typical acute IBD lesions (B) and flocks with typical chronic IBD lesions (C). Category A flocks achieved a net income per 1,000 birds which was 11% better (P<0.05) than category B flocks and 14% better (P<0.01) than category C flocks. The 85 broiler houses used by the surveyed flocks during production were similarly grouped into the three categories. Analysis of production data from 991 flocks comprising 14 million birds demonstrated that flocks reared in category A houses achieved a similar superiority in net income per 1,000 birds over those flocks reared in both category B and category C houses. Food conversion ratio and average weight per bird were also superior in flocks reared in category A houses. These findings suggest that IBD virus persisted from flock to flock in category B and category C houses. The differences in performance were greatly accentuated during the winter months. The results indicate that the presence of IBD virus infection accounts for about two-thirds of the reduced profitability achieved by broiler flocks in Northern Ireland during the winter.


Early diagnosis and monitoring of superficial transitional cell carcinoma by microsatellite analysis on urine sediment.
It has recently been shown that allelic abnormalities, detected by microsatellite analysis of the DNA extracted from urine sediment, can be successfully used for the detection of transitional cell carcinoma (TCC) of the bladder. The diagnostic accuracy of urinary cytology, urinary bladder cancer (UBC) marker, bladder tumor antigen (BTA) and microsatellite sequence alterations was compared in 42 patients who were recruited for the study. Of them, 30 had been diagnosed with TCC at cystoscopy plus biopsy (group A). Seven patients without any apparent lesions after trans-urethral resection (TUR) and 6 subsequent weeks of endovesical administration of bacillus Calmette-Guerin (BCG), had irritative symptoms. None of them had positive cytology or TCC bladder mucosa biopsies (group B). In the control group were 5 other subjects who were affected by benign prostatic hypertrophy and candidates for prostatectomy (group C). Urine and blood samples were obtained from all of the patients before surgery. Tumor tissue and normal mucosa samples were taken from groups A and C during surgery. Different urinary sediment analyses were performed by using both nuclear medicine and molecular tests. UBC and BTA-t analyses were carried out using monoclonal antibody tests while microsatellite analyses were performed using extracted DNA and electrophoresis of polymerase chain reaction (PCR) products on 13 different primers. Urinary cytological examinations were carried out using the Autocyte Preparation System(R). Urinary cytology confirmed the presence of TCC in 13.3% of patients. The BTA-t marker allowed the identification of 73.3% of cancers with 50% specificity; the UBC marker identified 63.3% of the cases with 41.6% specificity. Microsatellite analysis permitted the identification of 83.3% of the tumors with 100% specificity. DNA analysis demonstrated high sensitivity in patients affected by superficial (81.4%) or G1 (80%) tumors, even when cytological studies demonstrated little or no sensitivity. Microsatellite analysis is a highly-sensitive and specific marker for TCC diagnosis and its monitoring, especially in patients with low-stage and low-grade tumors. Other testing procedures failed to increase urinary cytological diagnostic significance.


Twenty-Five Year Secular Trends in Lipids and Modifiable Risk Factors in a Population-Based Biracial Cohort: The Coronary Artery Risk Development in Young Adults (CARDIA) Study, 1985-2011.
Cross-sectional analyses suggest that total and low-density lipoprotein cholesterol (LDL-c) trends that had been declining are now reversing. We examined longitudinal data from the Coronary Artery Risk Development in Young Adults (CARDIA) study to examine secular trends in total cholesterol, LDL-c, high-density lipoprotein cholesterol (HDL-c), and triglycerides over 25 years. We also assessed whether modifiable lifestyle factors (body mass index, physical activity, alcohol consumption, smoking, and lipid-lowering medications) are associated with these trends. CARDIA recruited 5115 black and white men and women ages 18 to 30 years from 4 US communities in 1985-1986, and re-examined them 5, 10, 15, 20, and 25 years later. Secular trends, modeled as age-matched time trends, were estimated using repeated-measures regression stratified on race and sex. Total cholesterol and LDL-c initially decreased ≈5 to 8 mg/dL between visits before plateauing and moving toward adverse trends in all groups, except black women, by year 25. HDL-c showed an upward secular trend of 1 to 3 mg/dL between visits starting at year 15 in all groups; triglyceride trends were largely flat. Obesity and use of lipid-lowering medications, which both increased over follow-up, had strong independent, but opposite, associations with lipid trends over time. In aggregate, associations of modifiable lifestyle factors counterbalanced one another, minimally influencing secular trends. Over 25 years, initially favorable trends in total cholesterol and LDL-c have leveled off and may be reversing, persisting after control for modifiable risk factors. Factors such as dietary changes over 25 years and poor adherence to medications are candidates for additional investigation.


The mediating role of eating psychopathology in the relationship between unhealthy core beliefs and feeding difficulties in a nonclinical group.
To determine whether maternal eating psychopathology mediates the relationship between unhealthy core beliefs and reports of child feeding difficulties. A community sample of 114 mothers of 65 male children and 49 female children between 4 months and 5 years completed the Eating Disorders Inventory-II, (Garner, Eating Disorder Inventory-2 Professional Manual, Odessa, 1991) the Child Feeding Assessment Questionnaire, (Harris and Booth, Monographs in Clinical Pediatrics, Vol 5, 1992) and the Young Schema Questionnaire (Short Form) (Young, Young's Schema Questionnaire: Short Form, Available in electronic form at, http://www.schematherapy.com, 1998). Drive for thinness significantly mediated the relationship between maternal defectiveness/shame beliefs and food refusal in mothers of daughters, but no mediational relationships were found for mothers of sons in this nonclinical group. Maternal drive for thinness mediates the effect of unhealthy beliefs on mothers' tendencies to report feeding difficulties in their daughters.


Pathology of the heart in Kawasaki disease.
Pathologic studies were done on 20 hearts of patients who had typical clinical signs and symptoms of Kawasaki disease. The cardiac lesions were classified according to the duration of illness at the time of death. Stage I (zero to nine days) was characterized by acute perivasculitis and vasculitis of the microvessels (arterioles, capillaries, and venules) and small arteries, and acute perivasculitis and endarteritis of the three major coronary arteries (MCAs). Pericarditis, myocarditis, inflammation of the atrioventricular conduction system, and endocarditis with valvulitis were also present. Stage II (12 to 25 days) was characterized by panvasculitis of the MCAs and aneurysm with thrombus in the stems. Myocarditis, coagulation necrosis, lesion of the conduction system, pericarditis, and endocarditis with valvulitis were also present. In stage III (28 to 31 days), granulation of the MCAs and disappearance of inflammation in the microvessels were noted. Patients in stage IV (40 days to 4 years) had scarring with severe stenosis in the MCAs. Fibrosis of the myocardium, coagulation necrosis, lesions of the conduction system, and endocardial fibroelastosis were also present. The features observed revealed Kawasaki disease to be acute and inflammatory. The angiitis begins in the microvessels and fibrinoid necrosis of the media is rare. The disease is one with a pathologic pattern previously unknown.


SIGN Guidelines for Scotland: BMD Versus FRAX Versus QFracture.
Scottish Intercollegiate Guidelines Network (SIGN) recently issued guidance on the management of osteoporosis and the prevention of fragility fractures. The aim of this paper was to critically review the guidance. The SIGN guidance utilises risk factors for fracture as an initial step for assessment, but recommends treatment only in individuals with a T-score of -2.5. There are many problems with the sole use of BMD as the sole gateway to treatment. Moreover, the assessment tools to determine risk (FRAX or QFracture) are not designed to detect osteoporosis but rather fracture risk. Whereas SIGN assumes that FRAX overestimates fracture probability, there are compelling reasons to believe that the disparity is related to the inadequate calibration of QFracture. The disparities make the use of a single threshold for BMD testing problematic. The SIGN guidance for men at high risk of fracture provides a set of confused and inconsistent recommendations that are in direct conflict with regulatory authorizations and is likely to increase further the large treatment gap in men. For women, the number of women eligible for treatment (i.e. with osteoporosis) is 81,700 with the use of FRAX but only 12,300 with QFracture representing 8.2 and 1.2 % of the total population at risk, respectively. We conclude that serious problems with the SIGN guidance preclude its implementation.


Integration of an [FeFe]-hydrogenase into the anaerobic metabolism of Escherichia coli.
Biohydrogen is a potentially useful product of microbial energy metabolism. One approach to engineering biohydrogen production in bacteria is the production of non-native hydrogenase activity in a host cell, for example Escherichia coli. In some microbes, hydrogenase enzymes are linked directly to central metabolism via diaphorase enzymes that utilise NAD+/NADH cofactors. In this work, it was hypothesised that heterologous production of an NAD+/NADH-linked hydrogenase could connect hydrogen production in an E. coli host directly to its central metabolism. To test this, a synthetic operon was designed and characterised encoding an apparently NADH-dependent, hydrogen-evolving [FeFe]-hydrogenase from Caldanaerobacter subterranus. The synthetic operon was stably integrated into the E. coli chromosome and shown to produce an active hydrogenase, however no H2 production was observed. Subsequently, it was found that heterologous co-production of a pyruvate::ferredoxin oxidoreductase and ferredoxin from Thermotoga maritima was found to be essential to drive H2 production by this system. This work provides genetic evidence that the Ca.subterranus [FeFe]-hydrogenase could be operating in vivo as an electron-confurcating enzyme.


An update on lipotoxic endoplasmic reticulum stress in pancreatic beta-cells.
The UPR (unfolded protein response) or ER (endoplasmic reticulum) stress response was first described 20 years ago. The field of ER stress has expanded tremendously since, moving from basic biology in yeast to human neurodegenerative, inflammatory, cardiovascular and neoplastic diseases. The ER stress response has also been implicated in diabetes development, affecting both insulin production by pancreatic beta-cells and insulin sensitivity in peripheral tissues. In the present mini-review, we focus on recent progress in the field of ER stress in pancreatic beta-cells. Recent advances in the understanding of lipotoxic ER stress and beta-cell recovery from ER stress are discussed.


The Relationship of Caregiving to Work Conflict and Supervisor Disclosure With Emotional, Physical, and Financial Strain in Employed Family Caregivers.
Objective: To determine whether employed family caregiver reports of caregiving to work conflict (CWC) are associated with emotional, physical, and financial strain, and whether organizational factors, including supervisor disclosure and caregiver-friendly workplace policies, attenuate these effects. Method: We examined 369 full-time employed caregivers of adults aged 50 years and above from the 2015 AARP and National Alliance for Caregiving population-based study, Caregiving in the United States, using ordinary least squares hierarchical regression and moderation analyses. Results: Regression analyses showed that caregiver reports of more CWC, in addition to disclosure of caregiving, were associated with greater emotional, physical, and financial strain after controlling for demographics and caregiving stressors, and workplace policies did not attenuate strain. Neither disclosure nor policies moderated the impact of CWC on caregiver strain. Discussion: Results suggest the importance of workplace strain in the caregiving stress process and suggest that disclosing caregiving responsibilities to supervisors should be closely examined.


Control of hepatic gluconeogenesis by Argonaute2.
The liver performs a central role in regulating energy homeostasis by increasing glucose output during fasting. Recent studies on Argonaute2 (Ago2), a key RNA-binding protein mediating the microRNA pathway, have illustrated its role in adaptive mechanisms according to changes in metabolic demand. Here we sought to characterize the functional role of Ago2 in the liver in the maintenance of systemic glucose homeostasis. We first analyzed Ago2 expression in mouse primary hepatocyte cultures after modulating extracellular glucose concentrations and in the presence of activators or inhibitors of glucokinase activity. We then characterized a conditional loss-of-function mouse model of Ago2 in liver for alterations in systemic energy metabolism. Here we show that Ago2 expression in liver is directly correlated to extracellular glucose concentrations and that modulating glucokinase activity is adequate to affect hepatic Ago2 levels. Conditional deletion of Ago2 in liver resulted in decreased fasting glucose levels in addition to reducing hepatic glucose production. Moreover, loss of Ago2 promoted hepatic expression of AMP-activated protein kinase α1 (AMPKα1) by de-repressing its targeting by miR-148a, an abundant microRNA in the liver. Deletion of Ago2 from hyperglycemic, obese, and insulin-resistant Lepob/ob mice reduced both random and fasted blood glucose levels and body weight and improved insulin sensitivity. These data illustrate a central role for Ago2 in the adaptive response of the liver to fasting. Ago2 mediates the suppression of AMPKα1 by miR-148a, thereby identifying a regulatory link between non-coding RNAs and a key stress regulator in the hepatocyte.


Intrahepatic transplanted islets in humans secrete insulin in a coordinate pulsatile manner directly into the liver.
Intrahepatic islet transplantation is an experimental therapy for type 1 diabetes. In the present studies, we sought to address the following questions: 1) In humans, do intrahepatic transplanted islets reestablish coordinated puslatile insulin secretion? and 2) To what extent is insulin secreted by intrahepatic transplanted islets delivered to the hepatic sinusoids (therefore effectively restoring a portal mode of insulin delivery) versus delivered to the hepatic central vein (therefore effectively providing a systemic form of insulin delivery)? To address the first question, we examined insulin concentration profiles in the overnight fasting state and during a hyperglycemic clamp ( approximately 150 mg/dl) in 10 recipients of islet transplants and 10 control subjects. To address the second question, we measured first-pass hepatic insulin clearance in two recipients of islet autografts after pancreatectomy for pancreatitis versus five control subjects by direct catheterization of the hepatic vein. We report that coordinate pulsatile insulin secretion is reestablished in islet transplant recipients and that glucose-mediated stimulation of insulin secretion is accomplished by amplification of insulin pulse mass. Direct hepatic catheterization studies revealed that intrahepatic islets in humans do deliver insulin directly to the hepatic sinusoid because approximately 80% of the insulin is extracted during first pass. In conclusion, intrahepatic islet transplantation effectively restores the liver to pulsatile insulin delivery.


Photo-induced sequence defined macromolecules via hetero bifunctional synthons.
We report the first photochemical protocol for the generation of sequence defined macromolecules employing two hetero bifunctional photoreactive synthons, exploiting the orthogonal nature of photochemical - via the use of caged dienes - and thermally driven ligation protocols. We demonstrate that the iterative alternating synthon addition to an initial bifunctional core under irradiation at ambient temperature enables the generation of a macromolecule with up to 10 units (M = 3231.58 g mol(-1), Đ = 1.00). The resulting macromolecules are monodisperse and feature absolute chain end fidelity. The unit-by-unit construction of the macromolecule is evidenced by Nuclear Magnetic Resonance Spectroscopy, Electrospray Ionization Mass Spectrometry and Size Exclusion Chromatography. The fundamental principle demonstrated herein paves the way for employing photochemical strategies for the design of sequence defined polymers.


Lifetime cost-effectiveness of calcineurin inhibitor withdrawal after de novo renal transplantation.
After renal transplantation, immunosuppressive regimens associated with high short-term survival rates are not necessarily associated with high long-term survival rates, suggesting that regimens may need to be optimized over time. Calcineurin inhibitor (CNI) withdrawal from a sirolimus-based immunosuppressive regimen may maximize the likelihood of long-term graft and patient survival by minimizing CNI-associated nephrotoxicity. In this study, a lifetime Markov model was created to compare the cost-effectiveness of a sirolimus-based CNI withdrawal regimen (sirolimus plus steroids) with other common CNI-containing regimens in adult de novo renal transplantation patients. Long-term graft survival was estimated by renal function and data from published studies and the US transplant registry, including short- and long-term outcomes, utility weights, and health-state costs were incorporated. Drug costs were based on average daily consumption and wholesale acquisition costs. The model suggests that treatment with sirolimus plus steroids is more efficacious and less costly than regimens consisting of a CNI, mycophenolate mofetil, and steroids; therefore, CNI withdrawal not only shows potential for long-term clinical benefits but also is expected to be cost-saving over a patient's life compared with the most commonly prescribed CNI-containing regimens.


Gene methylation parallelisms between peripheral blood cells and oral mucosa samples in relation to overweight.
Epigenetics has an important role in the regulation of metabolic adaptation to environmental modifications. In this sense, the determination of epigenetic changes in non-invasive samples during the development of metabolic diseases could play an important role in the procedures in primary healthcare practice. To help translate the knowledge of epigenetics to public health practice, the present study aims to explore the parallelism of methylation levels between white blood cells and buccal samples in relation to obesity and associated disorders. Blood and buccal swap samples were collected from a subsample of the Spanish cohort of the Food4Me study. Infinium HumanMethylation450 DNA Analysis was carried out for the determination of methylation levels. Standard deviation for β values method and concordance correlation analysis were used to select those CpG which showed best parallelism between samples. A total of 277 CpGs met the criteria and were selected for an enrichment analysis and a correlation analysis with anthropometrical and clinical parameters. From those selected CpGs, four presented high associations with BMI (cg01055691 in GAP43; r = -0.92 and rho = -0.84 for blood; r = -0.89 and rho = -0.83 for buccal sample), HOMA-IR (cg00095677 in ATP2A3; r = 0.82 and rho = -0.84 for blood; r = -0.8 and rho = -0.83 for buccal sample) and leptin (cg14464133 in ADARB2; r = -0.9182 and rho = -0.94 for blood; r = -0.893 and rho = -0.79 for buccal sample). These findings demonstrate the potential application of non-invasive buccal samples in the identification of surrogate epigenetic biomarkers and identify methylation sites in GAP43, ATP2A3 and ADARB2 genes as potential targets in relation to overweight management and insulin sensibility.


The wandering mind of men: ERP evidence for gender differences in attention bias towards attractive opposite sex faces.
To examine the time course and automaticity of our attention bias towards attractive opposite sex faces, event-related potentials (ERPs) were recorded from 20 males and 20 females while they carried out a covert orienting task. Faces that were high, low or average in attractiveness, were presented in focus of attention, but were unrelated to task goals. Across the entire sample larger P2 amplitudes were found in response to both attractive and unattractive opposite sex faces, presumably reflecting early implicit selective attention to distinctive faces. In male but not female participants this was followed by an increased late slow wave for the attractive faces, signifying heightened processing linked to motivated attention. This latter finding is consistent with sexual strategy theory, which suggests that men and women have evolved to pursue different mating strategies with men being more attentive to cues such as facial beauty. In general, our ERP results suggest that, in addition to threat-related stimuli, other evolutionary-relevant information is also prioritized by our attention systems.


Comment on "Exact solution of resonant modes in a rectangular resonator".
We comment on the recent Letter by J. Wu and A. Liu [Opt. Lett. 31, 1720 (2006)] in which an exact scalar solution to the resonant modes and the resonant frequencies in a two-dimensional rectangular microcavity were presented. The analysis is incorrect because (a) the field solutions were imposed to satisfy simultaneously both Dirichlet and Neumann boundary conditions at the four sides of the rectangle, leading to an overdetermined problem, and (b) the modes in the cavity were expanded using an incorrect series ansatz, leading to an expression for the mode fields that does not satisfy the Helmholtz equation.


Long-term trajectory of kidney function in autosomal-dominant polycystic kidney disease.
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by cyst and kidney growth, which is hypothesized to cause loss of functioning renal mass and eventually end-stage kidney disease. However, the time course of decline in glomerular filtration rate (GFR) is poorly defined. The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease study is a 14-year observational cohort study of 241 adults with ADPKD. As an estimate of the rate of kidney growth, participants were stratified into 5 subclasses based on baseline age and magnetic resonance imaging measurements of total kidney volume (TKV) according to the method of Irazabal. GFR trajectories spanning over four decades of life were reconstructed and fitted using mixed polynomial models, which were validated using data from the HALT-PKD study. GFR trajectories were nonlinear, with a period of relative stability in most participants, followed by accelerating decline. The shape and slope of these trajectories were strongly associated with baseline Irazabal class. Patients with PKD1 mutations had a steeper GFR decline than patients with PKD2 mutations or with no detected mutation, largely mediated by the effect of genotype on Irazabal class. Thus, GFR decline in ADPKD is nonlinear, and its trajectory throughout adulthood can be predicted from a single measurement of kidney volume. These models can be used for clinical prognostication, clinical trial design, and patient selection for clinical interventions. Our findings support a causal link between growth in kidney volume and GFR decline, adding support for the use of TKV as a surrogate endpoint in clinical trials.


Red squirrel middens influence abundance but not diversity of other vertebrates.
Some animals modify the environment in ways that can influence the resources available to other species. Because red squirrels (Tamiasciurus hudsonicus) create large piles of conifer-cone debris (middens) in which they store cones, squirrels concentrate resources that might affect biodiversity locally. To determine whether other animals are attracted to midden sites beyond their affinity for the same resources that attract red squirrels, we assessed associations between middens, mammals, and birds at population and community levels. We surveyed 75 middens where residency rates of red squirrels varied during the previous five years; sampling along this residency gradient permitted us to evaluate the influence of resources at middens beyond the influence of a resident squirrel. At each location, we quantified vegetation, landscape structure, abundance of conifer cones, and midden structure, and used capture-recapture, distance sampling, and remote cameras to quantify presence, abundance, and species richness of mammals and birds. Red squirrels and the resources they concentrated at middens influenced mammals and birds at the population scale and to a lesser extent at the community scale. At middens with higher residency rates of red squirrels, richness of medium and large mammals increased markedly and species richness of birds increased slightly. After accounting for local forest characteristics, however, only species richness of medium-to-large mammals was associated with a red squirrel being resident during surveys. In areas where red squirrels were resident during surveys or in areas with greater amounts of resources concentrated by red squirrels, abundances of two of four small mammal species and two of four bird species increased. We conclude that the presence of this ecosystem modifier and the resources it concentrates influence abundance of some mammals and birds, which may have implications for maintaining biodiversity across the wide geographic range inhabited by red squirrels and other larderhoarding animals.


Gut microbiota, dysbiosis and atrial fibrillation. Arrhythmogenic mechanisms and potential clinical implications.
Recent preclinical and observational cohort studies have implicated imbalances in gut microbiota composition as a contributor to atrial fibrillation (AF). The gut microbiota is a complex and dynamic ecosystem containing trillions of microorganisms, which produces bioactive metabolites influencing host health and disease development. In addition to host-specific determinants, lifestyle-related factors such as diet and drugs are important determinants of the gut microbiota composition. In this review, we discuss the evidence suggesting a potential bidirectional association between AF and gut microbiota, identifying gut microbiota-derived metabolites as possible regulators of the AF substrate. We summarize the effect of gut microbiota on the development and progression of AF risk factors, including heart failure, hypertension, obesity, and coronary artery disease. We also discuss the potential anti-arrhythmic effects of pharmacological and diet-induced modifications of gut microbiota composition, which may modulate and prevent the progression to AF. Finally, we highlight important gaps in knowledge and areas requiring future investigation. Although data supporting a direct relationship between gut microbiota and AF are very limited at the present time, emerging preclinical and clinical research dealing with mechanistic interactions between gut microbiota and AF is important as it may lead to new insights into AF pathophysiology and the discovery of novel therapeutic targets for AF.


The Perceptions of Physicians and Nurses Regarding the Establishment of Patient Safety in a Regional Teaching Hospital in Taiwan.
Physicians and nurses are core staff who are the first points of contact in care provision to patients. We aimed to examine physicians' and nurses' perceptions of patient safety in a case hospital by administering the Chinese Safety Attitude Questionnaire (CSAQ), developed from the Taiwan Joint Commission on Hospital Accreditation, in order to provide the patients with a safe environment and excellent medical service. An intra-organizational online survey was conducted. Confirmatory factor analysis (CFA) was first performed on the assessment of the measures for patient safety culture and seven dimensions with 33 items were identified. Pearson correlation analysis was subsequently used to examine the strength and direction of the relationships between seven dimensions of patient safety culture. A total of 800 questionnaires were issued and 405 valid questionnaires were collected, the effective response rate being 50.6%. The findings highlighted that safety climate (SC) was positively and significantly related to teamwork climate (TC) and perception of management (PM), whereas stress recognition (SR) was negatively related to burnout (BUR). Patient safety culture in healthcare organizations has been considered a critical issue for improving the quality of healthcare. This study further focused on the contribution of a better patient safety culture for healthcare organizations in Taiwan.


Examining the effects of urban agglomeration polders on flood events in Qinhuai River basin, China with HEC-HMS model.
The urban agglomeration polders type of flood control pattern is a general flood control pattern in the eastern plain area and some of the secondary river basins in China. A HEC-HMS model of Qinhuai River basin based on the flood control pattern was established for simulating basin runoff, examining the impact of urban agglomeration polders on flood events, and estimating the effects of urbanization on hydrological processes of the urban agglomeration polders in Qinhuai River basin. The results indicate that the urban agglomeration polders could increase the peak flow and flood volume. The smaller the scale of the flood, the more significant the influence of the polder was to the flood volume. The distribution of the city circle polder has no obvious impact on the flood volume, but has effect on the peak flow. The closer the polder is to basin output, the smaller the influence it has on peak flows. As the level of urbanization gradually improving of city circle polder, flood volumes and peak flows gradually increase compared to those with the current level of urbanization (the impervious rate was 20%). The potential change in flood volume and peak flow with increasing impervious rate shows a linear relationship.


[Antiphospholipid syndrome in neurology].
Antiphospholipid syndrome (APS) is an autoimmune disease with recurrent thromboses and pregnancy complications (90% are female patients) that can be primary and secondary (with concomitant autoimmune disease). Antiphospholipid antibodies are prothrombotic but also act directly with brain tissue. One clinical and one laboratory criterion is necessary for the diagnosis of APS. Positive serological tests have to be confirmed after at least 12 weeks. Clinical picture consists of thromboses in many organs and spontaneous miscarriages, sometimes thrombocytopaenia and haemolytic anaemia, but neurological cases are the most frequent: headaches, stroke, encephalopathy, seizures, visual disturbances, Sneddon syndrome, dementia, vertigo, chorea, balism, transitory global amnesia, psychosis, transversal myelopathy and Guillain-Barre syndrome. About 50% of strokes below 50 years of age are caused by APS. The first line of therapy in stroke is anticoagulation: intravenous heparin or low-weight heparins. In chronic treatment, oral anticoagulation and antiplatelet therapy are used, warfarin and aspirin, mostly for life. In resistant cases, corticosteroids, intravenous immunoglobulins and plasmapheresis are necessary. Prognosis is good in most patients but some are treatment-resistant with recurrent thrombotic events and eventually death.


Tandem high-dose chemotherapy and autologous stem cell transplantation in young children with atypical teratoid/rhabdoid tumor of the central nervous system.
The feasibility and effectiveness of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) were evaluated in children younger than 3 yr of age with atypical teratoid/rhabdoid tumors (ATRT). Tandem HDCT/autoSCT was administered following six cycles of induction chemotherapy. Radiotherapy (RT) was administered if the tumor relapsed or progressed, otherwise, it was administered after 3 yr of age. Tumors relapsed or progressed during induction chemotherapy in 5 of 9 patients enrolled; 3 of these 5 received tandem HDCT/autoSCT as a salvage treatment. One patient died from sepsis during induction chemotherapy. The remaining 3 patients proceeded to tandem HDCT/autoSCT; however, 2 of these patients showed tumor relapse/progression after tandem HDCT/autoSCT. All 7 relapses/progressions occurred at primary sites even in patients with leptomeningeal seeding. Toxicities during tandem HDCT/autoSCT were manageable. A total of 5 patients were alive with a median follow-up of 20 (range 16-70) months from diagnosis. Four of 5 patients who received RT after relapse/progression are alive. The probability of overall survival at 3 yr from diagnosis was 53.3% ± 17.3%. Our tandem HDCT/autoSCT is feasible; however, early administration of RT prior to tandem HDCT/autoSCT should be considered to improve the outcome after tandem HDCT/autoSCT.


Influence of Rotational Nucleosome Positioning on Transcription Start Site Selection in Animal Promoters.
The recruitment of RNA-Pol-II to the transcription start site (TSS) is an important step in gene regulation in all organisms. Core promoter elements (CPE) are conserved sequence motifs that guide Pol-II to the TSS by interacting with specific transcription factors (TFs). However, only a minority of animal promoters contains CPEs. It is still unknown how Pol-II selects the TSS in their absence. Here we present a comparative analysis of promoters' sequence composition and chromatin architecture in five eukaryotic model organisms, which shows the presence of common and unique DNA-encoded features used to organize chromatin. Analysis of Pol-II initiation patterns uncovers that, in the absence of certain CPEs, there is a strong correlation between the spread of initiation and the intensity of the 10 bp periodic signal in the nearest downstream nucleosome. Moreover, promoters' primary and secondary initiation sites show a characteristic 10 bp periodicity in the absence of CPEs. We also show that DNA natural variants in the region immediately downstream the TSS are able to affect both the nucleosome-DNA affinity and Pol-II initiation pattern. These findings support the notion that, in addition to CPEs mediated selection, sequence-induced nucleosome positioning could be a common and conserved mechanism of TSS selection in animals.


Therapeutic potentials of mesenchymal stem cells derived from human umbilical cord.
Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs), isolated from discarded extra-embryonic tissue after birth, are promising candidate source of mesenchymal stem cells (MSCs). Apart from their prominent advantages in abundant supply, painless collection, and faster self-renewal, hUC-MSCs have shown the potencies to differentiate into a variety of cells of three germ layers (such as bone, cartilage, adipose, skeletal muscle, cardiomyocyte, endothelium, hepatocyte-like cluster, islet-like cluster, neuron, astrocyte and oligodendrocyte), to synthesize and secret a set of trophic factors and cytokines, to support the expansion and function of other cells (like hematopoietic stem cells, embryonic stem cells, natural killer cells, islet-like cell clusters, neurons and glial cells), to migrate toward and home to pathological areas, and to be readily transfected with conventional methods. Two excellent previous reviews documenting the characteristics of this cell population with special emphasis on its niche, isolation, surface markers and primitive properties have been published recently. In this review, we will firstly give a brief introduction of this cell population, and subsequently dwell on the findings of differential capacities with emphasis on its therapeutic potentials.


How general practitioners perceive and assess self-care in patients with multiple chronic conditions: a qualitative study.
It is not known how general practitioners (GPs) perceive the concept of self-care and how they assess self-care ability in patients with multiple chronic conditions. As a part of the strategy to improve the care of people living with chronic conditions, disease management programs in Denmark require GPs and other health care workers to assess and support patients' self-care ability. The aim of the present study was to explore GPs' perceptions and assessment of self-care ability in patients with multiple chronic conditions who have difficulty following a given treatment. A qualitative study conducted through in-depth, semi-structured interviews with a purposive sample of 12 GPs in rural areas of Denmark with economically disadvantaged populations. The interviews involved 36 complex patient cases selected by the GPs themselves. Our analysis followed the principles of systematic text condensation. Most GPs in our study had a health-related perception of self-care, but some had a broader perception encompassing the situational context of the patient's life. The GPs' assessments of patients' self-care ability were based on information from the ongoing and often long-term relationships with the patients. GPs identified four major factors that influenced patients' self-care ability, which accumulated and fluctuated over time: multimorbidity, cognitive resources, material resources, and the patients' social contexts. The GPs in this study had dual perceptions of self-care, related to both the chronic health conditions and to the broader situational contexts of their patients' lives. GPs' assessments of self-care ability depended largely on their experiences from the doctor-patient relationship, and they emphasized that the factors affecting self-care ability were highly dynamic over the patient's lifetime. However, these findings might be resisted by the Danish disease management programs, which tend to have a static and more narrow, health-related view of patient self-care. The Danish programs require GPs to assess self-care ability upfront at the beginning of treatment and do not consider whether a relationship with the patient is established. If GPs' perceptions and assessments of self-care ability are not included in chronic disease management models, there is a risk that they vill be insufficiently implemented in general practice.


Age-dependent transition from cell-level to population-level control in murine intestinal homeostasis revealed by coalescence analysis.
In multi-cellular organisms, tissue homeostasis is maintained by an exquisite balance between stem cell proliferation and differentiation. This equilibrium can be achieved either at the single cell level (a.k.a. cell asymmetry), where stem cells follow strict asymmetric divisions, or the population level (a.k.a. population asymmetry), where gains and losses in individual stem cell lineages are randomly distributed, but the net effect is homeostasis. In the mature mouse intestinal crypt, previous evidence has revealed a pattern of population asymmetry through predominantly symmetric divisions of stem cells. In this work, using population genetic theory together with previously published crypt single-cell data obtained at different mouse life stages, we reveal a strikingly dynamic pattern of stem cell homeostatic control. We find that single-cell asymmetric divisions are gradually replaced by stochastic population-level asymmetry as the mouse matures to adulthood. This lifelong process has important developmental and evolutionary implications in understanding how adult tissues maintain their homeostasis integrating the trade-off between intrinsic and extrinsic regulations.


Genetic profiling and tailored therapy in asthma: are we there yet?
Asthma is characterized by reversible bronchial hyper-responsiveness and airway inflammation, and encompasses a wide variety of patients with different clinical phenotypes that display variable responses to therapy. The definition of genomic variation presented in the Human Genome Project has facilitated the development of genetic-guided therapy in various diseases, including asthma. Tailored therapy is a reality in many types of malignancies where specific gene mutations or molecular profiles are identified and used to make critical therapeutic decisions. Despite the identification of beta-adrenergic receptor polymorphisms by Liggett and colleagues during the 1990s, the pharmacogenetics of asthma is still in its infancy. There have been great advances in asthma pharmacogenetics and pharmacotherapy with the completion of several large trials highlighting the effects of genotype on response to asthma therapy. This review focuses on research articles that serve to emphasize the potential role of using genotyping as a tool to develop individualized patient treatment regimens for asthma, thus improving outcomes and limiting adverse effects of certain therapies.


Perception of conversations: the importance of semantics and intonation in children's development.
In conversations, adults readily detect and anticipate the end of a speaker's turn. However, little is known about the development of this ability. We addressed two important aspects involved in the perception of conversational turn taking: semantic content and intonational form. The influence of semantics was investigated by testing prelinguistic and linguistic children. The influence of intonation was tested by presenting participants with videos of two dyadic conversations: one with normal intonation and one with flattened (removed) intonation. Children of four different age groups--two prelinguistic groups (6- and 12-month-olds) and two linguistic groups (24- and 36-month-olds)--and an adult group participated. Their eye movements were recorded, and the frequency of anticipated turns was analyzed. Our results show that (a) the anticipation of turns was reliable only in 3-year-olds and adults, with younger children shifting their gaze between speakers regardless of the turn taking, and (b) only 3-year-olds anticipated turns better if intonation was normal. These results indicate that children anticipate turns in conversations in a manner comparable (but not identical) to adults only after they have developed a sophisticated understanding of language. In contrast to adults, 3-year-olds rely more strongly on prosodic information during the perception of conversational turn taking.


Condom use with steady partners among heterosexual people living with HIV in Europe: testing the information-motivation-behavioral skills model.
Guided by a modified information-motivation-behavioral skills model, this study identified predictors of condom use among heterosexual people living with HIV with their steady partners. Consecutive patients at 14 European HIV outpatient clinics received an anonymous, standardized, self-administered questionnaire between March and December 2007. Data were analyzed using descriptive statistics and two-step backward elimination regression analyses stratified by gender. The survey included 651 participants (n = 364, 56% women; n = 287, 44%). Mean age was 39 years for women and 43 years for men. Most had acquired HIV sexually and more than half were in a serodiscordant relationship. Sixty-three percent (n = 229) of women and 59% of men (n = 169) reported at least one sexual encounter with a steady partner 6 months prior to the survey. Fifty-one percent (n = 116) of women and 59% of men (n = 99) used condoms consistently with that partner. In both genders, condom use was positively associated with subjective norm conducive to condom use, and self-efficacy to use condoms. Having a partner whose HIV status was positive or unknown reduced condom use. In men, higher education and knowledge about condom use additionally increased condom use, while the use of erectile-enhancing medication decreased it. For women, HIV disclosure to partners additionally reduced the likelihood of condom use. Positive attitudes to condom use and subjective norm increased self-efficacy in both genders, however, a number of gender-related differences appeared to influence self-efficacy. Service providers should pay attention to the identified predictors of condom use and adopt comprehensive and gender-related approaches for preventive interventions with people living with HIV.


Aeolian process effects on vegetation communities in an arid grassland ecosystem.
Many arid grassland communities are changing from grass dominance to shrub dominance, but the mechanisms involved in this conversion process are not completely understood. Aeolian processes likely contribute to this conversion from grassland to shrubland. The purpose of this research is to provide information regarding how vegetation changes occur in an arid grassland as a result of aeolian sediment transport. The experimental design included three treatment blocks, each with a 25 × 50 m area where all grasses, semi-shrubs, and perennial forbs were hand removed, a 25 × 50 m control area with no manipulation of vegetation cover, and two 10 × 25 m plots immediately downwind of the grass-removal and control areas in the prevailing wind direction, 19° north of east, for measuring vegetation cover. Aeolian sediment flux, soil nutrients, and soil seed bank were monitored on each treatment area and downwind plot. Grass and shrub cover were measured on each grass-removal, control, and downwind plot along continuous line transects as well as on 5 × 10 m subplots within each downwind area over four years following grass removal. On grass-removal areas, sediment flux increased significantly, soil nutrients and seed bank were depleted, and Prosopis glandulosa shrub cover increased compared to controls. Additionally, differential changes for grass and shrub cover were observed for plots downwind of vegetation-removal and control areas. Grass cover on plots downwind of vegetation-removal areas decreased over time (2004-2007) despite above average rainfall throughout the period of observation, while grass cover increased downwind of control areas; P. glandulosa cover increased on plots downwind of vegetation-removal areas, while decreasing on plots downwind of control areas. The relationships between vegetation changes and aeolian sediment flux were significant and were best described by a logarithmic function, with decreases in grass cover and increases in shrub cover occurring with small increases in aeolian sediment flux.


Competency-Based Assessment Tool for Pediatric Tracheotomy: International Modified Delphi Consensus.
Create a competency-based assessment tool for pediatric tracheotomy. Blinded, modified, Delphi consensus process. Using the REDCap database, a list of 31 potential items was circulated to 65 expert surgeons who perform pediatric tracheotomy. In the first round, items were rated as "keep" or "remove," and comments were incorporated. In the second round, experts were asked to rate the importance of each item on a seven-point Likert scale. Consensus criteria were determined a priori with a goal of 7 to 25 final items. The first round achieved a response rate of 39/65 (60.0%), and returned questionnaires were 99.5% complete. All items were rated as "keep," and 137 comments were incorporated. In the second round, 30 task-specific and seven previously validated global rating items were distributed, and the response rate was 44/65 (67.7%), with returned questionnaires being 99.3% complete. Of the Task-Specific Items, 13 reached consensus, 10 were near consensus, and 7 did not achieve consensus. For the 7 previously validated global rating items, 5 reached consensus and two were near consensus. It is feasible to reach consensus on the important steps involved in pediatric tracheotomy using a modified Delphi consensus process. These items can now be considered to create a competency-based assessment tool for pediatric tracheotomy. Such a tool will hopefully allow trainees to focus on the important aspects of this procedure and help teaching programs standardize how they evaluate trainees during this procedure. 5 Laryngoscope, 130:2700-2707, 2020.


Does the home environment and the sex of the child modify the adverse effects of prenatal exposure to chlorpyrifos on child working memory?
Prenatal exposure to chlorpyrifos (CPF), an organophosphorus insecticide, has long been associated with delayed neurocognitive development and most recently with decrements in working memory at age 7. In the current paper, we expanded the previous work on CPF to investigate how additional biological and social environmental factors might create or explain differential neurodevelopmental susceptibility, focusing on main and moderating effects of the quality of the home environment (HOME) and child sex. We evaluate how the quality of the home environment (specifically, parental nurturance and environmental stimulation) and child sex interact with the adverse effects of prenatal CPF exposure on working memory at child age 7years. We did not observe a remediating effect of a high quality home environment (either parental nurturance or environmental stimulation) on the adverse effects of prenatal CPF exposure on working memory. However, we detected a borderline significant interaction between prenatal exposure to CPF and child sex (B (95% CI) for interaction term=-1.714 (-3.753 to 0.326)) suggesting males experience a greater decrement in working memory than females following prenatal CPF exposure. In addition, we detected a borderline interaction between parental nurturance and child sex (B (95% CI) for interaction term=1.490 (-0.518 to 3.499)) suggesting that, in terms of working memory, males benefit more from a nurturing environment than females. To our knowledge, this is the first investigation into factors that may inform an intervention strategy to reduce or reverse the cognitive deficits resulting from prenatal CPF exposure.


The eyes of Tullimonstrum reveal a vertebrate affinity.
Tullimonstrum gregarium is an iconic soft-bodied fossil from the Carboniferous Mazon Creek Lagerstätte (Illinois, USA). Despite a large number of specimens and distinct anatomy, various analyses over the past five decades have failed to determine the phylogenetic affinities of the 'Tully monster', and although it has been allied to such disparate phyla as the Mollusca, Annelida or Chordata, it remains enigmatic. The nature and phylogenetic affinities of Tullimonstrum have defied confident systematic placement because none of its preserved anatomy provides unequivocal evidence of homology, without which comparative analysis fails. Here we show that the eyes of Tullimonstrum possess ultrastructural details indicating homology with vertebrate eyes. Anatomical analysis using scanning electron microscopy reveals that the eyes of Tullimonstrum preserve a retina defined by a thick sheet comprising distinct layers of spheroidal and cylindrical melanosomes. Time-of-flight secondary ion mass spectrometry and multivariate statistics provide further evidence that these microbodies are melanosomes. A range of animals have melanin in their eyes, but the possession of melanosomes of two distinct morphologies arranged in layers, forming retinal pigment epithelium, is a synapomorphy of vertebrates. Our analysis indicates that in addition to evidence of colour patterning, ecology and thermoregulation, fossil melanosomes can also carry a phylogenetic signal. Identification in Tullimonstrum of spheroidal and cylindrical melanosomes forming the remains of retinal pigment epithelium indicates that it is a vertebrate; considering its body parts in this new light suggests it was an anatomically unusual member of total group Vertebrata.


Cellular immunity and acute hepatitis C infection.
Hepatitis C virus (HCV) infects an estimated 170 million people globally and persistent infection within the liver is the usual outcome of infection. The resulting liver disease leads to substantial morbidity and to date no vaccine exists. Furthermore the treatments available are frequently ineffective. A minority of those exposed will however successfully control the virus and the factors that dictate this remain elusive. The events that occur in the immediate and early phase post exposure are thought to play a crucial role in determining the outcome and virus specific T cells have a confirmed role in directing the immune response towards a successful outcome. An understanding of the T cell responses and the strategies, which allow the virus to evade these responses in the majority, is an essential prerequisite both for vaccine design and the development of therapeutic agents. We review here the characteristics of the cellular immune responses in acute infection and how the virus manages to undermine these responses and establish chronicity.


The estimation of unwanted fertility.
The estimation of unwanted fertility is a major objective of demographic surveys, including DHS surveys conducted in Asia, Africa, and Latin America. Levels and trends in unwanted fertility are important input to the formulation of population policy and the evaluation of family planning programs. Yet existing methods for estimating unwanted fertility are known to be defective, among other reasons because they rely on subjective data whose validity and reliability are questionable. In this article, we propose a new estimator of unwanted fertility-the "aggregate prospective estimator"--so named because it depends on the stated preference for another child at the time of the survey, the fertility-desires item consistently shown to possess the highest validity and reliability. Under reasonable assumptions, the aggregate prospective estimator produces less biased estimates of unwanted fertility than the most widely used existing methods. The new estimator has the limitation of generating only aggregate-level estimates, but such estimates are the primary data for policy formulation and program evaluation. The new estimator is presented in this article, along with an evaluation of its underlying assumptions and its sensitivity to several sources of error. In an illustrative application to recent DHS data from six countries, the new estimator yields substantially higher estimates of unwanted fertility than existing methods in all six countries.


Childhood maltreatment and clinical severity of treatment-resistant depression in a French cohort of outpatients (FACE-DR): One-year follow-up.
Childhood maltreatment is associated with major depressive disorder (MDD). It not only increases the risk of lifetime MDD, but it also aggravates its course. Among depressed patients, 20-30% of them experience treatment-resistance depression (TRD). We aimed to assess the association between childhood maltreatment, severity of depression in a unipolar TRD sample, and patient outcomes after one-year of follow-up. Patients were recruited for a prospective cohort from the French network of TRD expert centers. Depressive symptom severity was assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptomatology self-report (QIDS-SR). Childhood maltreatment was evaluated with the Childhood Trauma Questionnaire (CTQ). In total, 256 patients filled in the CTQ at baseline between 2012 and 2019. At baseline, the MADRS score was associated with CTQ score (β = .185; p = .004). QIDS was also associated with CTQ scores (β = .27; p < .001). Regarding the different subtypes of childhood maltreatment, MADRS was associated with physical (β = .21; p = .005) and sexual abuse (β = .22; p = .002), while QIDS with physical abuse (β = .304; p < .001) and physical neglect (β = .254; p < .001). However, we did not find any significant association focusing on the other types of traumas. During a 1-year follow-up focusing on remission, CTQ scores (baseline) were less important in remittent patients [n = 38; CTQ score = 39.26 (9.68)] than in nonremittent ones [n = 92; CTQ score = 46.02 (17.53)] (p = .027). There was no significant difference among remitters and nonremitters based on trauma subtypes. At baseline, CTQ scores had a significant influence on remission at 1 year (χ2 (1) = 5.57; p < .05). We lost this influence adding MADRS scores at baseline in the model (p = .063). We highlighted a significant association between the severity of depressive disorders and childhood maltreatment in the TRD population. Information about a history of childhood maltreatment helps in identifying individuals who could be less likely to go into remission after treatment.


Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel.
Although awareness of familial hypercholesterolemia (FH) is increasing, this common, potentially fatal, treatable condition remains underdiagnosed. Despite FH being a genetic disorder, genetic testing is rarely used. The Familial Hypercholesterolemia Foundation convened an international expert panel to assess the utility of FH genetic testing. The rationale includes the following: 1) facilitation of definitive diagnosis; 2) pathogenic variants indicate higher cardiovascular risk, which indicates the potential need for more aggressive lipid lowering; 3) increase in initiation of and adherence to therapy; and 4) cascade testing of at-risk relatives. The Expert Consensus Panel recommends that FH genetic testing become the standard of care for patients with definite or probable FH, as well as for their at-risk relatives. Testing should include the genes encoding the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9); other genes may also need to be considered for analysis based on patient phenotype. Expected outcomes include greater diagnoses, more effective cascade testing, initiation of therapies at earlier ages, and more accurate risk stratification.


Physiological demands of a swimming-based video game: Influence of gender, swimming background, and exergame experience.
Active video games (exergames) may provide short-term increase in energy expenditure. We explored the effects of gender and prior experience on aerobic and anaerobic energy systems contributions, and the activity profiles of 40 participants playing with a swimming exergame. We recorded oxygen consumption and assessed blood lactate after each swimming technique. We also filmed participants' gameplays, divided them into different phases and tagged them as active or inactive. Anaerobic pathway accounted for 8.9 ± 5.6% of total energy expenditure and although experienced players were less active compared to novice counterparts (η² < 0.15, p < 0.05), physiological measures were not different between performing groups. However, players with real-swimming experience during the first technique had higher heart rate (partial-η² = 0.09, p < 0.05). Our results suggest that short-term increase in physiological measures might happen in the beginning of gameplay because of unfamiliarity with the game mechanics. Despite low levels of activity compared to real sport, both aerobic and anaerobic energy systems should be considered in the evaluation of exergames. Game mechanics (involving the whole body) and strategies to minimize pragmatic play might be used for effective and meaningful game experience.


Praziquantel in the treatment of Schistosoma mansoni infection: comparison of 40 and 60 mg/kg bodyweight regimens.
Two different regimens of praziquantel, 40 mg/kg in a single dose and 60 mg/kg in two divided doses administered 6 hr apart, for the treatment of Schistosoma mansoni infection were compared in Abu Homos, Egypt. Participants in this study included 1,588 subjects of both sexes between five and 50 years old from two rural communities; 730 from Farshout and 858 from Om El-Laban. The prevalence of S. mansoni infection was 57.9% in Farshout and 69.0% in Om El-Laban. Infected subjects received 60 mg/kg of praziquantel in two divided doses 6 hr apart at Farshout and 40 mg/kg in a single dose at Om El-Laban. Eight to ten weeks after treatment, three stool samples were collected from each treated subject on three consecutive days and evaluated quantitatively by the modified Kato technique. The failure rate was significantly higher at Om El-Laban than at Farshout (14.5% versus 4.1% (odds ratio [OR] = 3.95, P < 0.0001). A significantly higher failure rate was consistent after adjustment for age and number of excreted S. mansoni eggs per gram of feces before treatment (OR = 3.75, P < 0.0001). In spite of differences among cure rates between the two regimens, we recommend 60 mg/kg on an individual basis but not for population treatment, since administration of a single dose of a drug is more practical than two doses given 6 hr apart.


[Occupational status and cancer of the oral cavity and oropharynx].
To estimate the risk of occupation in oral and oropharyngeal cancer, a hospital-based case-control study was conducted in Greater Metropolitan São Paulo, Brazil. The study included 325 cases and 468 controls, frequency-matched with cases by sex and age, and interviewed from January 1999 to March 2002. Occupational risks were examined by industry and job titles and restricted to males (266 cases, 362 controls). Odds ratios (OR) were calculated by unconditional logistic regression, controlling for age, smoking, and alcohol. Males working in vehicle maintenance shops (26 cases, 12 controls) showed adjusted OR = 2.45 (95%CI: 1.14-5.27), increasing among those employed 10 or more years (OR = 7.90; 95%CI: 2.03-30.72). Occupation as vehicle repair worker (14 cases, 7 controls) showed OR = 2.10 (95%CI: 0.78-5.68), increasing among workers exposed 10 or more years (OR = 26.21; 95%CI: 2.34-294.06). Other industries and occupations revealed OR higher than 1.5, but not statistically significant. In conclusion, employment in vehicle maintenance shops and occupation as vehicle repair worker showed risk for oral cancer, independently of smoking and alcohol. More prolonged exposure increased the risk.


Current medical research funding and frameworks are insufficient to address the health risks of global environmental change.
Three major international agreements signed in 2015 are key milestones for transitioning to more sustainable and resilient societies: the UN 2030 Agenda for Sustainable Development; the Sendai Framework for Disaster Risk Reduction; and the Paris Agreement under the United Nations Framework Convention on Climate Change. Together, these agreements underscore the critical importance of understanding and managing the health risks of global changes, to ensure continued population health improvements in the face of significant social and environmental change over this century. BODY: Funding priorities of major health institutions and organizations in the U.S. and Europe do not match research investments with needs to inform implementation of these international agreements. In the U.S., the National Institutes of Health commit 0.025 % of their annual research budget to climate change and health. The European Union Seventh Framework Programme committed 0.08 % of the total budget to climate change and health; the amount committed under Horizon 2020 was 0.04 % of the budget. Two issues apparently contributing to this mismatch are viewing climate change primarily as an environmental problem, and therefore the responsibility of other research streams; and narrowly framing research into managing the health risks of climate variability and change from the perspective of medicine and traditional public health. This reductionist, top-down perspective focuses on proximate, individual level risk factors. While highly successful in reducing disease burdens, this framing is insufficient to protect health and well-being over a century that will be characterized by profound social and environmental changes. International commitments in 2015 underscored the significant challenges societies will face this century from climate change and other global changes. However, the low priority placed on understanding and managing the associated health risks by national and international research institutions and organizations leaves populations poorly prepared to cope with changing health burdens. Risk-centered, systems approaches can facilitate understanding of the complex interactions and dependencies across environmental, social, and human systems. This understanding is needed to formulate effective interventions targeting socio-environmental factors that are as important for determining health burdens as are individual risk factors.


Atrophy rates accelerate in amnestic mild cognitive impairment.
We tested if rates of brain atrophy accelerate in individuals with amnestic mild cognitive impairment (aMCI) as they progress to typical late onset Alzheimer disease (AD). We included comparisons to subjects with aMCI who did not progress (labeled aMCI-S) and also to cognitively normal elderly subjects (CN). We studied 46 subjects with aMCI who progressed to AD (labeled aMCI-P), 46 CN, and 23 aMCI-S. All subjects must have had three or more serial MRI scans. Rates of brain shrinkage and ventricular expansion were measured across all available serial MRI scans in each subject. Change in volumes relative to the point at which subjects progressed to a clinical diagnosis of AD (the index date) was modeled in aMCI-P. Change in volumes relative to age was modeled in all three clinical groups. In aMCI-P the change in pre to post index rate (i.e., acceleration) of ventricular expansion was 1.7 cm(3)/year, and acceleration in brain shrinkage was 5.3 cm(3)/year. Brain volume declined and ventricular volume increased in all three groups with age. Volume changes decelerated with increasing age in aMCI-P, and to a lesser extent in aMCI-S, but were linear in the matched CN. Among all subjects with aMCI, rates of atrophy were greater in apolipoprotein E epsilon 4 carriers than noncarriers. Rates of atrophy accelerate as individuals progress from amnestic mild cognitive impairment (aMCI) to typical late onset Alzheimer disease (AD). Rates of atrophy are greater in younger than older subjects with aMCI who progressed to AD and subjects with aMCI who did not progress. We did not find that atrophy rates varied with age in 70- to 90-year-old cognitively normal subjects.


Global regulation of alternative splicing during myogenic differentiation.
Recent genome-wide analyses have elucidated the extent of alternative splicing (AS) in mammals, often focusing on comparisons of splice isoforms between differentiated tissues. However, regulated splicing changes are likely to be important in biological transitions such as cellular differentiation, or response to environmental stimuli. To assess the extent and significance of AS in myogenesis, we used splicing-sensitive microarray analysis of differentiating C2C12 myoblasts. We identified 95 AS events that undergo robust splicing transitions during C2C12 differentiation. More than half of the splicing transitions are conserved during differentiation of avian myoblasts, suggesting the products and timing of transitions are functionally significant. The majority of splicing transitions during C2C12 differentiation fall into four temporal patterns and were dependent on the myogenic program, suggesting that they are integral components of myogenic differentiation. Computational analyses revealed enrichment of many sequence motifs within the upstream and downstream intronic regions near the alternatively spliced regions corresponding to binding sites of splicing regulators. Western analyses demonstrated that several splicing regulators undergo dynamic changes in nuclear abundance during differentiation. These findings show that within a developmental context, AS is a highly regulated and conserved process, suggesting a major role for AS regulation in myogenic differentiation.


Development of HCV Therapeutic Vaccines Using Hp91 Peptide and Small Heat Shock Protein 20 as an Adjuvant.
Hepatitis C Virus (HCV) is a major cause of chronic liver disease in the world. Many studies showed that T-cell responses to HCV Nonstructural Protein 3 (NS3) play an important role in clearing acute HCV infections, thus NS3 can be considered as a suitable candidate antigen for development of a HCV therapeutic vaccine. We used Hp91 peptide and small heat shock protein 20 as an adjuvant for enhancement of NS3-specific humoral and cellular immunity in mice. In this study, various NS3 DNA and protein constructs were generated in eukaryotic and prokaryotic expression systems, and their potency in eliciting humoral and cellular immune responses was compared using small Heat shock protein 20 (Hsp20), the High Mobility Group Box 1 protein (HMGB1)-derived peptide (Hp91), and Freund's adjuvant in a BALB/c mouse model. Our results indicated that both the Hsp20 conjugated with NS3 protein and Hp91 significantly enhanced the levels of IgG2a, IgG2b and IFN-γ directed toward Th1 responses compared to other groups. Moreover, the immunostimulatory properties of Hp91 were significantly higher than Hsp20 and Freund's adjuvant in various immunization strategies. Mice immunized by NS3 protein formulated with Freund's adjuvant, and also mixed with Hp91 peptide showed higher secretion of Granzyme B than other groups. Hp91 peptide could develop NS3-specific B- and T-cell immune responses as a promising HCV therapeutic vaccine candidate in future.


Sensing with nanopores--the influence of asymmetric blocking on electrochemical redox cycling current.
Nanoporous redox cycling devices are highly efficient tools for the electrochemical sensing of redox-active molecules. By using a redox-active mediator, this concept can be exploited for the detection of molecular binding events via blocking of the redox cycling current within the nanopores. Here, we investigate the influence of different blocking scenarios inside a nanopore on the resulting redox cycling current. Our analysis is based on random walk simulations and finite element calculations. We distinguish between symmetric and asymmetric pore blocking and show that the current decrease is more pronounced in the case of asymmetric blocking reflecting the diffusion-driven pathway of the redox-active molecules. Using random walk simulations, we further study the impact of pore blocking in the frequency domain and identify relevant features of the power spectral density, which are of particular interest for sensing applications based on fluctuation analysis.


The WD-repeat protein superfamily in Arabidopsis: conservation and divergence in structure and function.
The WD motif (also known as the Trp-Asp or WD40 motif) is found in a multitude of eukaryotic proteins involved in a variety of cellular processes. Where studied, repeated WD motifs act as a site for protein-protein interaction, and proteins containing WD repeats (WDRs) are known to serve as platforms for the assembly of protein complexes or mediators of transient interplay among other proteins. In the model plant Arabidopsis thaliana, members of this superfamily are increasingly being recognized as key regulators of plant-specific developmental events. We analyzed the predicted complement of WDR proteins from Arabidopsis, and compared this to those from budding yeast, fruit fly and human to illustrate both conservation and divergence in structure and function. This analysis identified 237 potential Arabidopsis proteins containing four or more recognizable copies of the motif. These were classified into 143 distinct families, 49 of which contained more than one Arabidopsis member. Approximately 113 of these families or individual proteins showed clear homology with WDR proteins from the other eukaryotes analyzed. Where conservation was found, it often extended across all of these organisms, suggesting that many of these proteins are linked to basic cellular mechanisms. The functional characterization of conserved WDR proteins in Arabidopsis reveals that these proteins help adapt basic mechanisms for plant-specific processes. Our results show that most Arabidopsis WDR proteins are strongly conserved across eukaryotes, including those that have been found to play key roles in plant-specific processes, with diversity in function conferred at least in part by divergence in upstream signaling pathways, downstream regulatory targets and /or structure outside of the WDR regions.


Colorectal tumors from APC*I1307K carriers principally harbor somatic APC mutations outside the A8 tract.
APC*I1307K (c.3920T>A) is an inherited variant associated with colorectal tumour risk found almost exclusively in those of Ashkenazi Jewish ancestry. A single nucleotide substitution creates an oligo-adenine tract (A8) that appears to be inherently prone to further mis-pairing and slippage. The reported multiple tumor phenotype of carriers is not easily reconciled with molecular and population genetics data. We postulated that some c.3920T>A carriers with multiple adenomas have other unidentified APC germ line or somatic mutations. DNA from 82 colonic tumours and accompanying normal tissue collected from 29 carriers with multiple colorectal tumors was directly sequenced between codons 716 and 1604. We also assessed APC gene loss of heterozygosity. One patient (3.4%) was found to have an additional APC germ line mutation. Twenty-five of the tumours showed no significant somatic molecular change, 36 showed one change, 20 showed two, and one tumour showed more than 2 changes. Our data suggest a correlation between advancing histology and fewer beta-catenin binding sites remaining in the mutant proteins. There were no other common germ line variants identified within the region of the APC gene examined, suggesting that any effect from this region on tumour production is attributable to the c.3920T>A allele. Our findings further suggest the only somatic genetic change clearly attributable to the c.3920T>A mutation is the c.3924_3925insA.


Emergence of a new lineage of dengue virus type 2 identified in travelers entering Western Australia from Indonesia, 2010-2012.
Dengue virus (DENV) transmission is ubiquitous throughout the tropics. More than 70% of the current global dengue disease burden is borne by people who live in the Asia-Pacific region. We sequenced the E gene of DENV isolated from travellers entering Western Australia between 2010-2012, most of whom visited Indonesia, and identified a diverse array of DENV1-4, including multiple co-circulating viral lineages. Most viruses were closely related to lineages known to have circulated in Indonesia for some time, indicating that this geographic region serves as a major hub for dengue genetic diversity. Most notably, we identified a new lineage of DENV-2 (Cosmopolitan genotype) that emerged in Bali in 2011-2012. The spread of this lineage should clearly be monitored. Surveillance of symptomatic returned travellers provides important and timely information on circulating DENV serotypes and genotypes, and can reveal the herald wave of dengue and other emerging infectious diseases.


KNOTTED1 Cofactors, BLH12 and BLH14, Regulate Internode Patterning and Vein Anastomosis in Maize.
Monocot stems lack the vascular cambium and instead have characteristic structures in which intercalary meristems generate internodes and veins remain separate and scattered. However, developmental processes of these unique structures have been poorly described. BELL1-like homeobox (BLH) transcription factors (TFs) are known to heterodimerize with KNOTTED1-like homeobox TFs to play crucial roles in shoot meristem maintenance, but their functions are elusive in monocots. We found that maize (Zea mays) BLH12 and BLH14 have redundant but important roles in stem development. BLH12/14 interact with KNOTTED1 (KN1) in vivo and accumulate in overlapping domains in shoot meristems, young stems, and provascular bundles. Similar to kn1 loss-of-function mutants, blh12 blh14 (blh12/14) double mutants fail to maintain axillary meristems. Unique to blh12/14 is an abnormal tassel branching and precocious internode differentiation that results in dwarfism and reduced veins in stems. Micro-computed tomography observation of vascular networks revealed that blh12/14 double mutants had reduced vein number due to fewer intermediate veins in leaves and precocious anastomosis in young stems. Based on these results, we propose two functions of BLH12/14 during stem development: (1) maintaining intercalary meristems that accumulate KN1 and prevent precocious internode differentiation and (2) preventing precocious anastomosis of provascular bundles in young stems to ensure the production of sufficient independent veins.


Determining the in vivo regulation of cardiac pyruvate dehydrogenase based on label flux from hyperpolarised [1-13C]pyruvate.
Pyruvate dehydrogenase (PDH) is a key regulator of cardiac substrate selection and is regulated by both pyruvate dehydrogenase kinase (PDK)-mediated phosphorylation and feedback inhibition. The extent to which chronic upregulation of PDK protein levels, acutely increased PDK activity and acute feedback inhibition limit PDH flux remains unclear because existing in vitro assessment methods inherently disrupt the regulation of the enzyme complex. We have demonstrated previously that hyperpolarised (13)C-labelled metabolic tracers coupled with MRS can monitor flux through PDH in vivo. The aim of this study was to determine the relative contributions of acute and chronic changes in PDK and PDH activities to in vivo myocardial PDH flux. We examined both fed and fasted rats with either hyperpolarised [1-(13)C]pyruvate alone or hyperpolarised [1-(13)C]pyruvate co-infused with malate [to modulate mitochondrial nicotinamide adenine dinucleotide (NADH/NAD(+)) and acetyl-coenzyme A (acetyl-CoA)/CoA ratios, which alter both PDH activity and flux]. To confirm the metabolic fate of infused malate, we performed in vitro (1)H NMR spectroscopy on cardiac tissue extracts. We observed that, in fed rats, where PDH activity was high, the presence of malate increased PDH flux by 27%, whereas, in the fasted state, malate infusion had no effect on PDH flux. These observations suggest that pyruvate oxidation is limited by feedback inhibition from acetyl-CoA only when PDH activity is high. Therefore, in the case of PDH, and potentially other enzymes, hyperpolarised (13)C MRI can be used to assess noninvasively enzymatic regulation.


Multisite Quality Improvement Study of a Patient-Pathologist Consultation Program.
The aim of this multisite quality improvement study was to evaluate patients' experiences with the patient-centered pathology (PCP) consultation program and to determine whether PCP enhanced their care experience. Patients were invited to attend PCP consultations to review their pathology report and slides and have their questions answered by the pathologist privately, with the option to attend the appointment with family members or friends for support. A patient experience questionnaire (PEQ) was administered to patients, who participated voluntarily in the PCP, and survey data were collected and stored in REDCap. Statistical analysis was performed using SAS 9.4 (SAS Institute). Sixty-seven patients (95.5% female) aged 18 to 84 years across 4 institutions completed the PEQ. Overall, 58% and 15.8% of patients had breast and brain tumors, respectively, and 59.7% of tumors were newly diagnosed. Most patients thought it was important for them to learn as much as they could about their health condition. However, the majority of patients reported some degree of difficulty learning about their health condition based on written information, despite 97% having completed high school and/or further education. The majority of patients rated their pathologist as "excellent" across communication metrics. Ultimately, 100% of respondents were satisfied, found their visits to be useful, and would recommend the PCP to other patients. Patients found that personalized clinical encounters with pathologists improved their understanding of their health condition and their satisfaction with their care experience. Patients thought pathologists communicated respectfully, effectively, and empathetically.


Taming chlorine azide: access to 1,2-azidochlorides from alkenes.
The in situ preparation and trapping of chlorine azide provided a versatile one-pot method for the azidochlorination of alkenes. Gaseous ClN3 generated from sodium azide, hypochlorite, and acetic acid can be explosive if isolation is attempted. Instead, we generated the reagent in biphasic media in the presence of olefinic compounds dissolved in the organic layer or evenly emulsified throughout the solution in the absence of organic solvent. Under these conditions, ClN3 is created slowly and trapped immediately at the aqueous-organic interface. The resulting safe and reliable procedure provided 1,2-azidochloride derivatives of a variety of substrates, with evidence for both polar and radical mechanisms. Minor impurities characterized in the product mixtures indicated the presence of alternative reaction pathways deriving primarily from radical intermediates.


Evaluation of serum feline pancreatic lipase immunoreactivity and helical computed tomography versus conventional testing for the diagnosis of feline pancreatitis.
Serum feline trypsinogen-like immunoreactivity (fTLI) concentrations and abdominal ultrasound have facilitated the noninvasive diagnosis of pancreatitis in cats, but low sensitivities (33% and 20-35%, respectively) have been reported. A radioimmunoassay has been validated to measure feline pancreatic lipase immunoreactivity (fPLI), but the assay's sensitivity and specificity have not been established. In human beings, the sensitivity of computed tomography (CT) is high (75-90%), but in a study of 10 cats, only 2 had CT changes suggestive of pancreatitis. We prospectively evaluated these diagnostic tests in cats with and without pancreatitis. In all cats, serum was obtained for fTLI and fPLI concentrations, and pancreatic ultrasound images and biopsies were acquired. Serum fPLI concentrations (P< .0001) and ultrasound findings (P = .0073) were significantly different between healthy cats and cats with pancreatitis. Serum fTLI concentrations (P = .15) and CT measurements (P = .18) were not significantly different between the groups. The sensitivity of fTLI in cats with moderate to severe pancreatitis was 80%, and the specificity in healthy cats was 75%. Feline PLI concentrations were both sensitive in cats with moderate to severe pancreatitis (100%) and specific in the healthy cats (100%). Abdominal ultrasound was both sensitive in cats with moderate to severe pancreatitis (80%) and specific in healthy cats (88%). The high sensitivities of fPLI and abdominal ultrasound suggest that these tests should play an important role in the noninvasive diagnosis of feline pancreatitis. As suggested by a previous study, pancreatic CT is not a useful diagnostic test for feline pancreatitis.


Perioperative Outcomes and Management in Pediatric Complex Cranial Vault Reconstruction: A Multicenter Study from the Pediatric Craniofacial Collaborative Group.
The Pediatric Craniofacial Collaborative Group established the Pediatric Craniofacial Surgery Perioperative Registry to elucidate practices and outcomes in children with craniosynostosis undergoing complex cranial vault reconstruction and inform quality improvement efforts. The aim of this study is to determine perioperative management, outcomes, and complications in children undergoing complex cranial vault reconstruction across North America and to delineate salient features of current practices. Thirty-one institutions contributed data from June 2012 to September 2015. Data extracted included demographics, perioperative management, length of stay, laboratory results, and blood management techniques employed. Complications and outlier events were described. Outcomes analyzed included total blood donor exposures, intraoperative and perioperative transfusion volumes, and length of stay outcomes. One thousand two hundred twenty-three cases were analyzed: 935 children aged less than or equal to 24 months and 288 children aged more than 24 months. Ninety-five percent of children aged less than or equal to 24 months and 79% of children aged more than 24 months received at least one transfusion. There were no deaths. Notable complications included cardiac arrest, postoperative seizures, unplanned postoperative mechanical ventilation, large-volume transfusion, and unplanned second surgeries. Utilization of blood conservation techniques was highly variable. The authors present a comprehensive description of perioperative management, outcomes, and complications from a large group of North American children undergoing complex cranial vault reconstruction. Transfusion remains the rule for the vast majority of patients. The occurrence of numerous significant complications together with large variability in perioperative management and outcomes suggest targets for improvement.


Power spectral analysis for optical trap stiffness calibration from high-speed camera position detection with limited bandwidth.
The use of camera imaging enables trap calibration for multiple particles simultaneously. For stiff traps, however, blur from image integration time affects the detected particle positions significantly. In this paper we use power spectral analysis to calibrate stiff optical traps, taking the effects of blur, aliasing and position detection error into account, as put forward by Wong and Halvorsen [Opt. Express 14, 12517 (2006)]. We find agreement with simultaneously obtained photodiode data and the expected relation of corner frequency fc with laser power, up to fc = 3.6 kHz for a Nyquist frequency of 1.25 kHz. Spectral analysis enables easy identification of the contribution of noise. We demonstrate the utility of our approach with simultaneous calibration of multiple holographic optical traps.


Evaluation of three oligonucleotide primer sets in PCR for the identification of Burkholderia cepacia and their differentiation from Burkholderia gladioli.
To evaluate three oligonucleotide primer pairs--two specific for 16S and 23S rRNA sequences of Burkholderia cepacia, and the third specific for internal transcribed spacer region of 16S-23S sequences of B gladioli--for the identification and differentiation of reference and clinical strains of these and other species. The three primers sets were applied in polymerase chain reaction (PCR) to a collection of 177 clinical isolates submitted for identification from diagnostic laboratories as presumed B cepacia. At an annealing temperature of 63 degrees C, all eight B cepacia and four B gladioli reference strains reacted with their specific primers. B vandii was the only other species that was positive with both B cepacia primers but five Burkholderia or Ralstonia species reacted with one of these primers. Seventy eight isolates were typical of B cepacia in biochemical tests and 75 of these reacted with specific primers; three, however, were positive with the B gladioli primers. Fifteen asaccharolytic isolates were confirmed as B cepacia by PCR but other non-fermenting Gram negative species were negative with each of the primers. PCR using 16S rRNA sequences is recommended for identification of B cepacia that give atypical results in biochemical tests.


A century of increasing pine density and associated shifts in understory plant strategies.
We analyzed one of the longest-term ecological data sets to evaluate how forest overstory structure is related to herbaceous understory plant strategies in a ponderosa pine forest. Eighty-two permanent 1-m2 chart quadrats that were established as early as 1912 were remeasured in 2007. We reconstructed historical forest structure using dendrochronological techniques. Ponderosa pine basal area increased from an average of 4 m2/ha in the early 1900s to 29 m2/ha in 2007. Understory plant foliar cover declined by 21%, species richness declined by two species per square meter, and functional diversity also declined. The relative cover of C4 graminoids decreased by 18% and C3 graminoids increased by 19%. Herbaceous plant species with low leaf and fine root nitrogen concentrations, low specific leaf area, high leaf dry matter content, large seed mass, low specific root length, short maximum height, and early flowering date increased in relative abundance in sites where pine basal area increased the most. Overall, we observed a long-term shift in composition toward more conservative shade- and stress-tolerant herbaceous species. Our analysis of temporal changes in plant strategies provides a general framework for evaluating compositional and functional changes in terrestrial plant communities.


Labor and skills gap analysis of the biomedical research workforce.
The United States has experienced an unsustainable increase of the biomedical research workforce over the past 3 decades. This expansion has led to a myriad of consequences, including an imbalance in the number of researchers and available tenure-track faculty positions, extended postdoctoral training periods, increasing age of investigators at first U.S. National Institutes of Health R01 grant, and exodus of talented individuals seeking careers beyond traditional academe. Without accurate data on the biomedical research labor market, challenges will remain in resolving these problems and in advising trainees of viable career options and the skills necessary to be productive in their careers. We analyzed workforce trends, integrating both traditional labor market information and real-time job data. We generated a profile of the current biomedical research workforce, performed labor gap analyses of occupations in the workforce at regional and national levels, and assessed skill transferability between core and complementary occupations. We conclude that although supply into the workforce and the number of job postings for occupations within that workforce have grown over the past decade, supply continues to outstrip demand. Moreover, we identify practical skill sets from real-time job postings to optimally equip trainees for an array of careers to effectively meet future workforce demand.-Mason, J. L., Johnston, E., Berndt, S., Segal, K., Lei, M., Wiest, J. S. Labor and skills gap analysis of the biomedical research workforce.


South Africa's nutritional transition: overweight, obesity, underweight and stunting in female primary school learners in rural KwaZulu-Natal, South Africa.
Malnutrition substantially impacts the health outcomes of children. Globally, the childhood prevalence of overweight and obesity has increased, while underweight and stunting (though decreasing) continues to pose a major public health challenge. In low- to middle-income countries, a mixed pattern of over- and undernutrition (nutritional transition) can exist in communities. To describe the prevalence of malnutrition among female learners in the Nongoma and Ceza districts in Zululand, KwaZulu-Natal (KZN). We performed a secondary analysis of anthropometric data collected during the 2011 HPV Vaccination Demonstration Project. School health teams, comprising trained nurses, measured the height (in cm) and weight (in kg) of 963 female learners in 31 primary schools. Internationally accepted standardised measures were used as cut-offs for defining overweight, obesity, underweight and stunting. We found evidence of both under- and overnutrition. Overall, 9% of female learners were overweight, 3.8% obese, 4% underweight and 9.2% stunted (using WHO/NCHS criteria). The highest levels of stunting were in the 11 - 12-year age groups, of underweight in the 10-year age group, of overweight and obesity in the 9 - 10-year age groups. Moreover, a proportion of underweight (17.4%), overweight (11.1%) and obese (22.9%) learners were also stunted. Our study describes the prevalence of overweight and obesity, wasting and stunting of female learners in KZN and suggests the presence of a nutritional transition in these rural communities; however, further studies are needed. Our findings emphasise the need for health promotion and education programs in schools.


Enhancing the phase profile and contrast of an interferogram by polarization recording in bacteriorhodopsin.
Interferometry is a technique for reconstructing the profiles of phase objects. We present a novel interferometric setup for generating interferograms with doubled phase profile and enhanced contrast compared with the standard interferogram. The proposed system consists of a two-beam interferometer in which the reference and test waves are circularly polarized orthogonally to each other. They are superposed upon a bacteriorhodopsin film, creating a polarization grating that is distorted by the phase of the test object. This polarization pattern is read by a polarized He-Ne beam. We show analytically and experimentally that, when the zero diffraction order is removed, an interferogram with doubled phase profile and enhanced contrast is obtained.