Hydrous silicate melts and the deep mantle H2O cycle

We report ab initio atomistic simulations of hydrous silicate melts under deep upper mantle to shallow lower mantle conditions and use them to parameterise density and viscosity across the ternary system MgO-SiO2-H2O (MSH). On the basis of phase relations in the MSH system, primary hydrous partial melts of the mantle have 40-50 mol% H2O. Our results show that these melts will be positively buoyant at the upper and lower boundaries of the mantle transition zone except in very iron-rich compositions, where ≳ 75% Mg is substituted by Fe. Hydrous partial melts will also be highly inviscid. Our results indicate that if melting occurs when wadsleyite transforms to olivine at 410 km, melts will be buoyant and ponding of melts is unexpected. Box models of mantle circulation incorporating the upward mobility of partial melts above and below the transition zone suggest that the upper mantle becomes efficiently hydrated at the expense of the transition zone such that large differences in H2O concentration between the upper mantle, transition zone and lower mantle are difficult to maintain on timescales of mantle recycling. The MORB source mantle with ∼0.02-0.04 wt% H2O may be indicative of the H2O content of the transition zone and lower mantle, resulting in a bulk mantle H2O content of the order 0.5 to 1 ocean mass, which is consistent with geochemical constraints and estimates of subduction ingassing

Acute response and chronic stimulus for cardiac structural and functional adaptation in a professional boxer.

The individual response to acute and chronic changes in cardiac structure and function to intense exercise training is not fully understood and therefore evidence in this setting may help to improve the timing and interpretation of pre-participation cardiac screening. The following case report highlights an acute increase in right ventricular (RV) size and a reduction in left ventricular (LV) basal radial function with concomitant increase at the mid-level in response to a week's increase in training volume in a professional boxer. These adaptations settle by the second week; however, chronic physiological adaptation occurs over a 12-week period. Electrocardiographic findings demonstrate an acute lateral T-wave inversion at 1 week, which revert to baseline for the duration of training. It appears that a change in training intensity and volume generates an acute response within the RV that acts as a stimulus for chronic adaptation in this professional boxer

Habitual physical activity is associated with the maintenance of neutrophil migratory dynamics in healthy older adults

Background: Dysfunctional neutrophils with advanced age are a hallmark of immunesenescence. Reduced migration and bactericidal activity increase the risk of infection. It remains unclear why neutrophil dysfunction occurs with age. Physical activity and structured exercise have been suggested to improve immune function in the elderly. The aim of this study was to assess a comprehensive range of neutrophil functions and determine their association with habitual physical activity. Method: Physical activity levels were determined in 211 elderly (67 ± 5 years) individuals by 7-days of accelerometry wear. Twenty of the most physically active men and women were matched for age and gender to twenty of the least physically active individuals. Groups were compared for neutrophil migration, phagocytosis, oxidative burst, cell surface receptor expression, metabolic health parameters and systemic inflammation. Groups were also compared against ten young participants (23 ± 4 years). Results: The most active group completed over twice as many steps/day as the least active group (p0.05). These differences remained after adjusting for BMI, body fat and plasma metabolic markers which were different between groups. Correlations revealed that steps/day, higher adiponectin and lower insulin were positively associated with migratory ability (p0.05 for both). CD11b was higher in the most active group compared to the least active (p=0.048). No differences between activity groups or young controls were observed for neutrophil phagocytosis or oxidative 2  burst in response to E.coli (p>0.05). The young group had lower concentrations of IL- 6, IL-8, MCP-1, CRP, IL-10 and IL-13 (p<0.05 for all) with no differences between the two older groups. Conclusion: These data suggest that impaired neutrophil migration, but not bactericidal function, in older adults may be, in part, the result of reduced physical activity. A 2-fold difference in physical activity is associated with better preserved neutrophil migratory dynamics in healthy older people. As a consequence increasing habitual physical activity may be beneficial for neutrophil mediated immunity

Answer changing in multiple choice assessment change that answer when in doubt – and spread the word!

<p>Abstract</p> <p>Background</p> <p>Several studies during the last decades have shown that answer changing in multiple choice examinations is generally beneficial for examinees. In spite of this the common misbelief still prevails that answer changing in multiple choice examinations results in an increased number of wrong answers rather than an improved score. One suggested consequence of newer studies is that examinees should be informed about this misbelief in the hope that this prejudice might be eradicated. This study aims to confirm data from previous studies about the benefits of answer changing as well as pursue the question of whether students informed about the said advantageous effects of answer changing would indeed follow this advice and change significantly more answers. Furthermore a look is cast on how the overall examination performance and mean point increase of these students is affected.</p> <p>Methods</p> <p>The answer sheets to the end of term exams of 79 3^rdyear medical students at the University of Munich were analysed to confirm the benefits of answer changing. Students taking the test were randomized into two groups. Prior to taking the test 41 students were informed about the benefits of changing answers after careful reconsideration while 38 students did not receive such information. Both groups were instructed to mark all answer changes made during the test.</p> <p>Results</p> <p>Answer changes were predominantly from wrong to right in full accordance with existing literature resources. It was shown that students who had been informed about the benefits of answer changing when in doubt changed answers significantly more often than students who had not been informed. Though students instructed on the benefits of changing answers scored higher in their exams than those not instructed, the difference in point increase was not significant.</p> <p>Conclusion</p> <p>Students should be informed about the benefits of changing initial answers to multiple choice questions once when in reasonable doubt about these answers. Furthermore, reconsidering answers should be encouraged as students will heed the advice and change more answers than students not so instructed.</p

Yield of Clinical Screening for Hypertrophic Cardiomyopathy in Child First-Degree Relatives: Evidence for a Change in Paradigm

Background: Hypertrophic Cardiomyopathy (HCM) is a heritable myocardial disease with age related penetrance. Current guidelines recommend clinical screening of relatives from the age of 10 years onwards but the clinical value of this approach has not been systematically evaluated. Methods: Anonymized, clinical data were collected from children referred for family screening between 1994-2017 following diagnosis of HCM in a first-degree relative. Results: 1198 consecutive children (aged ≤ 18 years) from 594 families underwent serial evaluation [median 3.5 years (IQR, 1.2-7)]; 32 individuals met diagnostic criteria at baseline (median maximal LV wall thickness (MLVWT) 13mm (IQR, 8-21mm)) and 25 additional patients developed HCM during follow up. Median age at diagnosis was 10 years (IQR 4-13); 44 (72%) were 12 years or younger. Median age of affected patients at last follow up was 14 years (IQR 9.5-18.2). A family history of childhood HCM was more common in those patients diagnosed with HCM (n=32, 56%, VS n=257, 23% P <0.001). 18 patients (32%) were started on medication for symptoms, 2 (4%) underwent a septal myectomy, 14 (25%) received an implantable cardioverter defibrillator, 1 underwent cardiac transplantation, 2 had a resuscitated cardiac arrest and 1 died following a cerebrovascular accident. Conclusions: Almost 5% of first-degree child relatives undergoing screening meet diagnostic criteria for HCM at first or subsequent evaluations, with the majority presenting as preadolescents; a diagnosis in a child first-degree relative is made in 8% of families screened. The phenotype of familial HCM in childhood is varied and includes severe disease, suggesting that clinical screening should commence at a younger ag

Use of NON-PARAMETRIC Item Response Theory to develop a shortened version of the Positive and Negative Syndrome Scale (PANSS)

<p>Abstract</p> <p>Background</p> <p>Nonparametric item response theory (IRT) was used to examine (a) the performance of the 30 Positive and Negative Syndrome Scale (PANSS) items and their options ((levels of severity), (b) the effectiveness of various subscales to discriminate among differences in symptom severity, and (c) the development of an abbreviated PANSS (Mini-PANSS) based on IRT and a method to link scores to the original PANSS.</p> <p>Methods</p> <p>Baseline PANSS scores from 7,187 patients with Schizophrenia or Schizoaffective disorder who were enrolled between 1995 and 2005 in psychopharmacology trials were obtained. Option characteristic curves (OCCs) and Item Characteristic Curves (ICCs) were constructed to examine the probability of rating each of seven options within each of 30 PANSS items as a function of subscale severity, and summed-score linking was applied to items selected for the Mini-PANSS.</p> <p>Results</p> <p>The majority of items forming the Positive and Negative subscales (i.e. 19 items) performed very well and discriminate better along symptom severity compared to the General Psychopathology subscale. Six of the seven Positive Symptom items, six of the seven Negative Symptom items, and seven out of the 16 General Psychopathology items were retained for inclusion in the Mini-PANSS. Summed score linking and linear interpolation was able to produce a translation table for comparing total subscale scores of the Mini-PANSS to total subscale scores on the original PANSS. Results show scores on the subscales of the Mini-PANSS can be linked to scores on the original PANSS subscales, with very little bias.</p> <p>Conclusions</p> <p>The study demonstrated the utility of non-parametric IRT in examining the item properties of the PANSS and to allow selection of items for an abbreviated PANSS scale. The comparisons between the 30-item PANSS and the Mini-PANSS revealed that the shorter version is comparable to the 30-item PANSS, but when applying IRT, the Mini-PANSS is also a good indicator of illness severity.</p

DNA resection in eukaryotes: deciding how to fix the break

DNA double-strand breaks are repaired by different mechanisms, including homologous recombination and nonhomologous end-joining. DNA-end resection, the first step in recombination, is a key step that contributes to the choice of DSB repair. Resection, an evolutionarily conserved process that generates single-stranded DNA, is linked to checkpoint activation and is critical for survival. Failure to regulate and execute this process results in defective recombination and can contribute to human disease. Here, I review recent findings on the mechanisms of resection in eukaryotes, from yeast to vertebrates, provide insights into the regulatory strategies that control it, and highlight the consequences of both its impairment and its deregulation

Item response analysis of the Positive and Negative Syndrome Scale

<p>Abstract</p> <p>Background</p> <p>Statistical models based on item response theory were used to examine (a) the performance of individual Positive and Negative Syndrome Scale (PANSS) items and their options, (b) the effectiveness of various subscales to discriminate among individual differences in symptom severity, and (c) the appropriateness of cutoff scores recently recommended by Andreasen and her colleagues (2005) to establish symptom remission.</p> <p>Methods</p> <p>Option characteristic curves were estimated using a nonparametric item response model to examine the probability of endorsing each of 7 options within each of 30 PANSS items as a function of standardized, overall symptom severity. Our data were baseline PANSS scores from 9205 patients with schizophrenia or schizoaffective disorder who were enrolled between 1995 and 2003 in either a large, naturalistic, observational study or else in 1 of 12 randomized, double-blind, clinical trials comparing olanzapine to other antipsychotic drugs.</p> <p>Results</p> <p>Our analyses show that the majority of items forming the Positive and Negative subscales of the PANSS perform very well. We also identified key areas for improvement or revision in items and options within the General Psychopathology subscale. The Positive and Negative subscale scores are not only more discriminating of individual differences in symptom severity than the General Psychopathology subscale score, but are also more efficient on average than the 30-item total score. Of the 8 items recently recommended to establish symptom remission, 1 performed markedly different from the 7 others and should either be deleted or rescored requiring that patients achieve a lower score of 2 (rather than 3) to signal remission.</p> <p>Conclusion</p> <p>This first item response analysis of the PANSS supports its sound psychometric properties; most PANSS items were either very good or good at assessing overall severity of illness. These analyses did identify some items which might be further improved for measuring individual severity differences or for defining remission thresholds. Findings also suggest that the Positive and Negative subscales are more sensitive to change than the PANSS total score and, thus, may constitute a "mini PANSS" that may be more reliable, require shorter administration and training time, and possibly reduce sample sizes needed for future research.</p

Rationality versus reality: the challenges of evidence-based decision making for health policy makers

<p>Abstract</p> <p>Background</p> <p>Current healthcare systems have extended the evidence-based medicine (EBM) approach to health policy and delivery decisions, such as access-to-care, healthcare funding and health program continuance, through attempts to integrate valid and reliable evidence into the decision making process. These policy decisions have major impacts on society and have high personal and financial costs associated with those decisions. Decision models such as these function under a shared assumption of rational choice and utility maximization in the decision-making process.</p> <p>Discussion</p> <p>We contend that health policy decision makers are generally unable to attain the basic goals of evidence-based decision making (EBDM) and evidence-based policy making (EBPM) because humans make decisions with their naturally limited, faulty, and biased decision-making processes. A cognitive information processing framework is presented to support this argument, and subtle cognitive processing mechanisms are introduced to support the focal thesis: health policy makers' decisions are influenced by the subjective manner in which they individually process decision-relevant information rather than on the objective merits of the evidence alone. As such, subsequent health policy decisions do not necessarily achieve the goals of evidence-based policy making, such as maximizing health outcomes for society based on valid and reliable research evidence.</p> <p>Summary</p> <p>In this era of increasing adoption of evidence-based healthcare models, the rational choice, utility maximizing assumptions in EBDM and EBPM, must be critically evaluated to ensure effective and high-quality health policy decisions. The cognitive information processing framework presented here will aid health policy decision makers by identifying how their decisions might be subtly influenced by non-rational factors. In this paper, we identify some of the biases and potential intervention points and provide some initial suggestions about how the EBDM/EBPM process can be improved.</p