1,344 research outputs found

    Prosocial and antisocial children's perceptions of peers' motives for prosocial behaviours

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    This study investigated whether peer-nominated prosocial and antisocial children have different perceptions of the motives underlying peers' prosocial actions. Eighty-seven children, aged 10-12 years old, completed peer-nomination measures of social behaviour. On the basis of numbers of social nominations received, a subsample of 51 children (32 who were peer-nominated as 'prosocial', and 18 who were peer-nominated as 'antisocial') then recorded their perceptions of peers' motives for prosocial behaviours. Expressed motives were categorized predominantly into three categories, coinciding with Turiel's (1978) 'moral', 'conventional', and 'personal domains'. Results indicate that children's social reputation is associated with the extent to which they perceive peers' prosocial motives as 'personal' or 'moral', with more prosocial children attributing moral motives, and more antisocial children attributing personal motives. Although traditionally Turiel's domain theory has been used to understand 'antisocial' children's behaviour, the current findings suggest that 'prosocial' children's behaviour may also be related to domains of judgment

    A cellular automaton model of crystalline cellulose hydrolysis by cellulases

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    <p>Abstract</p> <p>Background</p> <p>Cellulose from plant biomass is an abundant, renewable material which could be a major feedstock for low emissions transport fuels such as cellulosic ethanol. Cellulase enzymes that break down cellulose into fermentable sugars are composed of different types - cellobiohydrolases I and II, endoglucanase and β-glucosidase - with separate functions. They form a complex interacting network between themselves, soluble hydrolysis product molecules, solution and solid phase substrates and inhibitors. There have been many models proposed for enzymatic saccharification however none have yet employed a cellular automaton approach, which allows important phenomena, such as enzyme crowding on the surface of solid substrates, denaturation and substrate inhibition, to be considered in the model.</p> <p>Results</p> <p>The Cellulase 4D model was developed <it>de novo </it>taking into account the size and composition of the substrate and surface-acting enzymes were ascribed behaviors based on their movements, catalytic activities and rates, affinity for, and potential for crowding of, the cellulose surface, substrates and inhibitors, and denaturation rates. A basic case modeled on literature-derived parameters obtained from <it>Trichoderma reesei </it>cellulases resulted in cellulose hydrolysis curves that closely matched curves obtained from published experimental data. Scenarios were tested in the model, which included variation of enzyme loadings, adsorption strengths of surface acting enzymes and reaction periods, and the effect on saccharide production over time was assessed. The model simulations indicated an optimal enzyme loading of between 0.5 and 2 of the base case concentrations where a balance was obtained between enzyme crowding on the cellulose crystal, and that the affinities of enzymes for the cellulose surface had a large effect on cellulose hydrolysis. In addition, improvements to the cellobiohydrolase I activity period substantially improved overall glucose production.</p> <p>Conclusions</p> <p>Cellulase 4D simulates the enzymatic hydrolysis of cellulose to glucose by surface and solution phase-acting enzymes and accounts for complex phenomena that have previously not been included in cellulose hydrolysis models. The model is intended as a tool for industry, researchers and educators alike to explore options for enzyme engineering and process development and to test hypotheses regarding cellulase mechanisms.</p

    The structure of the hexameric atrazine chlorohydrolase AtzA

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    Atrazine chlorohydrolase (AtzA) was discovered and purified in the early 1990s from soil that had been exposed to the widely used herbicide atrazine. It was subsequently found that this enzyme catalyzes the first and necessary step in the breakdown of atrazine by the soil organism Pseudomonas sp. strain ADP. Although it has taken 20 years, a crystal structure of the full hexameric form of AtzA has now been obtained. AtzA is less well adapted to its physiological role (i.e. atrazine dechlorination) than the alternative metal-dependent atrazine chlorohydrolase (TrzN), with a substrate-binding pocket that is under considerable strain and for which the substrate is a poor fit

    Functional polymorphisms in the P2X7 receptor gene are associated with stress fracture injury

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    Context: Military recruits and elite athletes are susceptible to stress fracture injuries. Genetic predisposition has been postulated to have a role in their development. The P2X7 receptor (P2X7R) gene, a key regulator of bone remodelling, is a genetic candidate that may contribute to stress fracture predisposition. Objective: To evaluate the putative contribution of P2X7R to stress fracture injury in two separate cohorts, military personnel and elite athletes. Methods: In 210 Israeli Defence Forces (IDF) military conscripts, stress fracture injury was diagnosed (n=43) based on symptoms and a positive bone scan. In a separate cohort of 518 elite athletes, self-reported medical imaging scan-certified stress fracture injuries were recorded (n=125). Non-stress fracture controls were identified from these cohorts who had a normal bone scan or no history or symptoms of stress fracture injury. Study participants were genotyped for functional SNPs within the P2X7R gene using proprietary fluorescence-based competitive allele-specific PCR assay. Pearson Chi-square (χ2) tests, corrected for multiple comparisons, were used to assess associations in genotype frequencies. Results: The variant allele of P2X7R SNP rs3751143 (Glu496Ala- loss of function) was associated with stress fracture injury, while the variant allele of rs1718119 (Ala348Thr- gain of function) was associated with a reduced occurrence of stress fracture injury in military conscripts (P<0.05). The association of the variant allele of rs3751143 with stress fractures was replicated in elite athletes (P<0.05), whereas the variant allele of rs1718119 was also associated with reduced multiple stress fracture cases in elite athletes (P<0.05). Conclusions: The association between independent P2X7R polymorphisms with stress fracture prevalence supports the role of a genetic predisposition in the development of stress fracture injury

    The vulnerability of public spaces: challenges for UK hospitals under the 'new' terrorist threat

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    This article considers the challenges for hospitals in the United Kingdom that arise from the threats of mass-casualty terrorism. Whilst much has been written about the role of health care as a rescuer in terrorist attacks and other mass-casualty crises, little has been written about health care as a victim within a mass-emergency setting. Yet, health care is a key component of any nation's contingency planning and an erosion of its capabilities would have a significant impact on the generation of a wider crisis following a mass-casualty event. This article seeks to highlight the nature of the challenges facing elements of UK health care, with a focus on hospitals both as essential contingency responders under the United Kingdom's civil contingencies legislation and as potential victims of terrorism. It seeks to explore the potential gaps that exist between the task demands facing hospitals and the vulnerabilities that exist within them

    Patients with treated indolent lymphomas immunized with BNT162b2 have reduced anti-spike neutralizing IgG to SARS-CoV-2 variants, but preserved antigen-specific T cell responses

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    Patients with indolent lymphoma undertaking recurrent or continuous B cell suppression are at risk of severe COVID-19. Patients and healthy controls (HC; N = 13) received two doses of BNT162b2: follicular lymphoma (FL; N = 35) who were treatment naïve (TN; N = 11) or received immunochemotherapy (ICT; N = 23) and Waldenström's macroglobulinemia (WM; N = 37) including TN (N = 9), ICT (N = 14), or treated with Bruton's tyrosine kinase inhibitors (BTKi; N = 12). Anti-spike immunoglobulin G (IgG) was determined by a high-sensitivity flow-cytometric assay, in addition to live-virus neutralization. Antigen-specific T cells were identified by coexpression of CD69/CD137 and CD25/CD134 on T cells. A subgroup (N = 29) were assessed for third mRNA vaccine response, including omicron neutralization. One month after second BNT162b2, median anti-spike IgG mean fluorescence intensity (MFI) in FL ICT patients (9977) was 25-fold lower than TN (245 898) and HC (228 255, p =.0002 for both). Anti-spike IgG correlated with lymphocyte count (r =.63; p =.002), and time from treatment (r =.56; p =.007), on univariate analysis, but only with lymphocyte count on multivariate analysis (p =.03). In the WM cohort, median anti-spike IgG MFI in BTKi patients (39 039) was reduced compared to TN (220 645, p =.0008) and HC (p <.0001). Anti-spike IgG correlated with neutralization of the delta variant (r =.62, p <.0001). Median neutralization titer for WM BTKi (0) was lower than HC (40, p <.0001) for early-clade and delta. All cohorts had functional T cell responses. Median anti-spike IgG decreased 4-fold from second to third dose (p =.004). Only 5 of 29 poor initial responders assessed after third vaccination demonstrated seroconversion and improvement in neutralization activity, including to the omicron variant

    Profiles and outcome of traditional healing practices for severe mental illnesses in two districts of Eastern Uganda

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    Background : The WHO estimates that more than 80% of African populations attend traditional healers for health reasons and that 40%–60% of these have some kind of mental illness. However, little is known about the profiles and outcome of this traditional approach to treatment. Objective : The purpose of this study was to describe the profiles and outcome of traditional healing practices for severe mental illnesses in Jinja and Iganga districts in the Busoga region of Eastern Uganda. Methods : Four studies were conducted. Study I used focus group discussions (FGDs) with case vignettes with local community members and traditional healers to explore the lay concepts of psychosis. Studies II and III concerned a cross-sectional survey of patients above 18 years at the traditional healer's shrines and study IV was made on a prospective cohort of patients diagnosed with psychosis in study III. Manual content analysis was used in study I; quantitative data in studies II, III, and IV were analyzed at univariate, bivariate, and multivariate levels to determine the association between psychological distress and socio-demographic factors; for study IV, factors associated with outcome were analyzed. One-way ANOVA for independent samples was the analysis used in Study IV. Results : The community gave indigenous names to psychoses (mania, schizophrenia, and psychotic depression) and had multiple explanatory models for them. Thus multiple solutions for these problems were sought. Of the 387 respondents, the prevalence of psychological distress was 65.1%, where 60.2% had diagnosable current mental illness, and 16.3% had had one disorder in their lifetime. Over 80% of patients with psychosis used both biomedical and traditional healing systems. Those who combined these two systems seemed to have a better outcome. All the symptom scales showed a percentage reduction of more than 20% at the 3- and 6-month follow-ups. Conclusion : Traditional healers shoulder a large burden of care of patients with mental health problems. This calls for all those who share the goal of improving the mental health of individuals to engage with traditional healers

    Gastrin-releasing peptide receptor-based targeting using bombesin analogues is superior to metabolism-based targeting using choline for in vivo imaging of human prostate cancer xenografts

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    Purpose: Prostate cancer (PC) is a major health problem. Overexpression of the gastrin-releasing peptide receptor (GRPR) in PC, but not in the hyperplastic prostate, provides a promising target for staging and monitoring of PC. Based on the assumption that cancer cells have increased metabolic activity, metabolism-based tracers are also being used for PC imaging. We compared GRPR-based targeting using the68Ga-labelled bombesin analogue AMBA with metabolism-based tar

    Cofactor tail length modulates catalysis of bacterial F420-dependent oxidoreductases

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    F420 is a microbial cofactor that mediates a wide range of physiologically important and industrially relevant redox reactions, including in methanogenesis and tetracycline biosynthesis. This deazaflavin comprises a redox-active isoalloxazine headgroup conjugated to a lactyloligoglutamyl tail. Here we studied the catalytic significance of the oligoglutamate chain, which differs in length between bacteria and archaea. We purified short-chain F420 (two glutamates) from a methanogen isolate and long-chain F420 (five to eight glutamates) from a recombinant mycobacterium, confirming their different chain lengths by HPLC and LC/MS analysis. F420 purified from both sources was catalytically compatible with purified enzymes from the three major bacterial families of F420-dependent oxidoreductases. However, long-chain F420 bound to these enzymes with a six- to ten-fold higher affinity than short-chain F420. The cofactor side chain also significantly modulated the kinetics of the enzymes, with long-chain F420 increasing the substrate affinity (lower Km) but reducing the turnover rate (lower kcat) of the enzymes. Molecular dynamics simulations and comparative structural analysis suggest that the oligoglutamate chain of F420 makes dynamic electrostatic interactions with conserved surface residues of the oxidoreductases while the headgroup binds the catalytic site. In conjunction with the kinetic data, this suggests that electrostatic interactions made by the oligoglutamate tail result in higher-affinity, lower-turnover catalysis. Physiologically, we propose that bacteria have selected for long-chain F420 to better control cellular redox reactions despite tradeoffs in catalytic rate. Conversely, this suggests that industrial use of shorter-length F420 will greatly increase the rates of bioremediation and biocatalysis processes relying on purified F420-dependent oxidoreductasesThis work was supported by a CSIRO Office of the Chief Executive Postdoctoral Fellowship and an ARC DECRA Fellowship (DE170100310) awarded to CG, a Marsden Grant (GNS-035) awarded to CC, and Australian Research Council grants (DE120102673, DP130102144) awarded to CJ

    Quality Improvement Intervention for Reduction of Redundant Testing

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    Laboratory data are critical to analyzing and improving clinical quality. In the setting of residual use of creatine kinase M and B isoenzyme testing for myocardial infarction, we assessed disease outcomes of discordant creatine kinase M and B isoenzyme +/troponin I (−) test pairs in order to address anticipated clinician concerns about potential loss of case-finding sensitivity following proposed discontinuation of routine creatine kinase and creatine kinase M and B isoenzyme testing. Time-sequenced interventions were introduced. The main outcome was the percentage of cardiac marker studies performed within guidelines. Nonguideline orders dominated at baseline. Creatine kinase M and B isoenzyme testing in 7496 order sets failed to detect additional myocardial infarctions but was associated with 42 potentially preventable admissions/quarter. Interruptive computerized soft stops improved guideline compliance from 32.3% to 58% (P \u3c .001) in services not receiving peer leader intervention and to \u3e80% (P \u3c .001) with peer leadership that featured dashboard feedback about test order performance. This successful experience was recapitulated in interrupted time series within 2 additional services within facility 1 and then in 2 external hospitals (including a critical access facility). Improvements have been sustained postintervention. Laboratory cost savings at the academic facility were estimated to be ≥US$635 000 per year. National collaborative data indicated that facility 1 improved its order patterns from fourth to first quartile compared to peer norms and imply that nonguideline orders persist elsewhere. This example illustrates how pathologists can provide leadership in assisting clinicians in changing laboratory ordering practices. We found that clinicians respond to local laboratory data about their own test performance and that evidence suggesting harm is more compelling to clinicians than evidence of cost savings. Our experience indicates that interventions done at an academic facility can be readily instituted by private practitioners at external facilities. The intervention data also supplement existing literature that electronic order interruptions are more successful when combined with modalities that rely on peer education combined with dashboard feedback about laboratory order performance. The findings may have implications for the role of the pathology laboratory in the ongoing pivot from quantity-based to value-based health care
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