Modeling micro-heterogeneity in mixtures: the role of many body terms

A two-component interaction model is introduced herein, which allows to describe macroscopic miscibility with various modes of tunable micro-segregation, ranging from phase separation to micro-segregation, and in excellent agreement for structural quantities obtained from simulations and the liquid state hypernetted-chain like integral equation theory. The model is based on the conjecture that the many-body correlation bridge function term in the closure relation can be divided into one part representing the segregation effects, which are modeled herein, and the usual part representing random many body fluctuations. Furthermore, the model allows to fully neglect these second contributions, thus increasing the agreement between the simulations and the theory. The analysis of the retained part of the many body correlations gives important clues about how to model the many body bridge functions for more realistic systems exhibiting micro-segregation, such as aqueous mixtures.Comment: 6 figure

Can we use biomarkers of coagulation to predict which patients with foot and ankle injury will develop vein thrombosis?

Background Our aim was to determine whether plasma levels of Tissue Factor (TF), Vascular Cell Adhesion Molecule 1 (VCAM-1), Interleukin 6 (IL-6) or D-dimer after foot and ankle injury could predict which patients would develop deep vein thrombosis (DVT). Methods Patients aged 18–60 years with acute foot and ankle injury had venous blood sample to measure TF, VCAM-1, IL-6 and D-dimer within 3 days of injury. Patients had bilateral lower limb venous ultrasound to assess for DVT on discharge from clinic. Results 21 of 77 patients were found to have DVT (27%). There was no statistically significant association between levels of TF, VCAM-1, IL-6 or D-dimer and subsequent development of DVT. Conclusion Tissue Factor (TF), Vascular Cell Adhesion Molecule-1 (VCAM-1), Interleukin-6 (IL-6) and D-dimer levels were not associated with development deep vein thrombosis in patients with acute foot and ankle injury

Neuraminidase inhibitors for treatment and prophylaxis of influenza in children: systematic review and meta-analysis of randomised controlled trials

Objective To assess the effects of the neuraminidase inhibitors oseltamivir and zanamivir in treatment of children with seasonal influenza and prevention of transmission to children in households

The effect of active toe movement (AToM) on calf pump function and deep vein thrombosis in patients with acute foot and ankle trauma treated with cast - a prospective randomized study

Background Patients with foot and ankle trauma treated with cast are advised to perform toe movements to prevent venous thromboembolism (VTE). Our aim was to determine the effect of active toe movement on asymptomatic deep vein thrombosis (DVT) and venous calf pump function. Methods Patients aged 18–60 years with acute foot and ankle trauma requiring below knee non weight bearing cast were randomized to intervention (regular active toe movement) or control groups (n = 100). Patients had bilateral lower limb venous ultrasound to assess for DVT on discharge from clinic. Patients requiring chemical thromboprophylaxis were excluded. Results 78 completed the study. 27% sustained asymptomatic DVT, with no statistically significant difference in calf pump function or DVT incidence between groups. All DVT's occurred in the injured lower limb. Conclusion Active toe movement is not a viable strategy for thromboprophylaxis in patients with acute foot and ankle trauma treated with cast

Protocol: Child and adolescent mental health and psychosocial support interventions: an evidence and gap map of low- and middle-income countries

This is the protocol for a Campbell review. The objective of this evidence and gap map is to provide an overview of the existing evidence on the effectiveness of interventions aimed at promoting mental health and reducing or preventing mental health conditions among children and adolescents in low- and middle-income countries

Negligible risk of inducing resistance in Mycobacterium tuberculosis with single-dose rifampicin as post-exposure prophylaxis for leprosy

Post-exposure prophylaxis (PEP) for leprosy is administered as one single dose of rifampicin (SDR) to the contacts of newly diagnosed leprosy patients. SDR reduces the risk of developing leprosy among contacts by around 60 % in the first 2-3 years after receiving SDR. In countries where SDR is currently being implemented under routine programme conditions in defined areas, questions were raised by health authorities and professional bodies about the possible risk of inducing rifampicin resistance among the M. tuberculosis strains circulating in these areas. This issue has not been addressed in scientific literature to date. To produce an authoritative consensus statement about the risk that SDR would induce rifampicin-resistant tuberculosis, a meeting was convened with tuberculosis (TB) and leprosy experts. The experts carefully reviewed and discussed the available evidence regarding the mechanisms and risk factors for the development of (multi) drug-resistance in M. tuberculosis with a view to the special situation of the use of SDR as PEP for leprosy. They concluded that SDR given to contacts of leprosy patients, in the absence of symptoms of active TB, poses a negligible risk of generating resistance in M. tuberculosis in individuals and at the population level. Thus, the benefits of SDR prophylaxis in reducing the risk of developing leprosy in contacts of new leprosy patients far outweigh the risks of generating drug resistance in M. tuberculosis

A structural and dynamic model for the assembly of Replication Protein A on single-stranded DNA

Replication Protein A (RPA), the major eukaryotic single stranded DNA-binding protein, binds to exposed ssDNA to protect it from nucleases, participates in a myriad of nucleic acid transactions and coordinates the recruitment of other important players. RPA is a heterotrimer and coats long stretches of single-stranded DNA (ssDNA). The precise molecular architecture of the RPA subunits and its DNA binding domains (DBDs) during assembly is poorly understood. Using cryo electron microscopy we obtained a 3D reconstruction of the RPA trimerisation core bound with ssDNA (∼55 kDa) at ∼4.7 Å resolution and a dimeric RPA assembly on ssDNA. FRET-based solution studies reveal dynamic rearrangements of DBDs during coordinated RPA binding and this activity is regulated by phosphorylation at S178 in RPA70. We present a structural model on how dynamic DBDs promote the cooperative assembly of multiple RPAs on long ssDNA

The Evidence Base for Interventions Delivered to Children in Primary Care: An Overview of Cochrane Systematic Reviews

Background: As a first step in developing a framework to evaluate and improve the quality of care of children in primary care there is a need to identify the evidence base underpinning interventions relevant to child health. Our objective was to identify all Cochrane systematic reviews relevant to the management of childhood conditions in primary care and to assess the extent to which Cochrane reviews reflect the burden of childhood illness presenting in primary care.Methodology/Principal Findings: We used the Cochrane Child Health Field register of child-relevant systematic reviews to complete an overview of Cochrane reviews related to the management of children in primary care. We compared the proportion of systematic reviews with the proportion of consultations in Australia, US, Dutch and UK general practice in children. We identified 396 relevant systematic reviews; 385 included primary studies on children while 251 undertook a meta-analysis. Most reviews (n=218, 55%) focused on chronic conditions and over half (n=216, 57%) evaluated drug interventions. Since 2000, the percentage of pediatric primary care relevant reviews only increased by 2% (7% to 9%) compared to 18% (10% to 28%) in all child relevant reviews. Almost a quarter of reviews (n=78, 23%) were published on asthma treatments which only account for 3-5% of consultations. Conversely, 15-23% of consultations are due to skin conditions yet they represent only 7% (n=23) of reviews.Conclusions/Significance: Although Cochrane systematic reviews focus on clinical trials and do not provide a comprehensive picture of the evidence base underpinning the management of children in primary care, the mismatch between the focus of the published research and the focus of clinical activity is striking. Clinical trials are an important component of the evidence based and the lack of trial evidence to demonstrate intervention effectiveness in substantial areas of primary care for children should be addressed.</p

Evaluation of a Hydrogel-Based Diagnostic Approach for the Point-of-Care Based Detection of Neisseria gonorrhoeae

Eleven primer pairs were developed for the identification of Neisseria gonorrhoeae. The sensitivity and specificity of these primers were evaluated by Real Time (RT)-PCR melt curve analyses with DNA from 145 N. gonorrhoeae isolates and 40 other Neisseria or non-Neisseria species. Three primer pairs were further evaluated in a hydrogel-based RT-PCR detection platform, using DNA extracted from 50 N. gonorrhoeae cultures. We observed 100% sensitivity and specificity in the hydrogel assay, confirming its potential as a point-of-care test (POCT) for N. gonorrhoeae diagnosis