Expressions for forces and torques in molecular simulations using rigid bodies

Expressions for intermolecular forces and torques, derived from pair potentials between rigid non-spherical units, are presented. The aim is to give compact and clear expressions, which are easily generalised, and which minimise the risk of error in writing molecular dynamics simulation programs. It is anticipated that these expressions will be useful in the simulation of liquid crystalline systems, and in coarse-grained modelling of macromolecules

Regulation of B cell fate by chronic activity of the IgE B cell receptor.

IgE can trigger potent allergic responses, yet the mechanisms regulating IgE production are poorly understood. Here we reveal that IgE+ B cells are constrained by chronic activity of the IgE B cell receptor (BCR). In the absence of cognate antigen, the IgE BCR promoted terminal differentiation of B cells into plasma cells (PCs) under cell culture conditions mimicking T cell help. This antigen-independent PC differentiation involved multiple IgE domains and Syk, CD19, BLNK, Btk, and IRF4. Disruption of BCR signaling in mice led to consistently exaggerated IgE+ germinal center (GC) B cell but variably increased PC responses. We were unable to confirm reports that the IgE BCR directly promoted intrinsic apoptosis. Instead, IgE+ GC B cells exhibited poor antigen presentation and prolonged cell cycles, suggesting reduced competition for T cell help. We propose that chronic BCR activity and access to T cell help play critical roles in regulating IgE responses

Quantum Common Causes and Quantum Causal Models

Reichenbach’s principle asserts that if two observed variables are found to be correlated, then there should be a causal explanation of these correlations. Furthermore, if the explanation is in terms of a common cause, then the conditional probability distribution over the variables given the complete common cause should factorize. The principle is generalized by the formalism of causal models, in which the causal relationships among variables constrain the form of their joint probability distribution. In the quantum case, however, the observed correlations in Bell experiments cannot be explained in the manner Reichenbach’s principle would seem to demand. Motivated by this, we introduce a quantum counterpart to the principle. We demonstrate that under the assumption that quantum dynamics is fundamentally unitary, if a quantum channel with input A and outputs B and C is compatible with A being a complete common cause of B and C , then it must factorize in a particular way. Finally, we show how to generalize our quantum version of Reichenbach’s principle to a formalism for quantum causal models and provide examples of how the formalism works

Cost-effectiveness analysis of preoperative transfusion in patients with sickle cell disease using evidence from the TAPS trial.

The study's objective was to assess the cost-effectiveness of preoperative transfusion compared with no preoperative transfusion in patients with sickle cell disease undergoing low- or medium-risk surgery. Seventy patients with sickle cell disease (HbSS/Sß(0) thal genotypes) undergoing elective surgery participated in a multicentre randomised trial, Transfusion Alternatives Preoperatively in Sickle Cell Disease (TAPS). Here, a cost-effectiveness analysis based on evidence from that trial is presented. A decision-analytic model is used to incorporate long-term consequences of transfusions and acute chest syndrome. Costs and health benefits, expressed as quality-adjusted life years (QALYs), are reported from the 'within-trial' analysis and for the decision-analytic model. The probability of cost-effectiveness for each form of management is calculated taking into account the small sample size and other sources of uncertainty. In the range of scenarios considered in the analysis, preoperative transfusion was more effective, with the mean improvement in QALYs ranging from 0.018 to 0.206 per patient, and also less costly in all but one scenario, with the mean cost difference ranging from -£813 to £26. All scenarios suggested preoperative transfusion had a probability of cost-effectiveness >0.79 at a cost-effectiveness threshold of £20 000 per QALY

Modelling and simulating change in reforesting mountain landscapes using a social-ecological framework

Natural reforestation of European mountain landscapes raises major environmental and societal issues. With local stakeholders in the Pyrenees National Park area (France), we studied agricultural landscape colonisation by ash (Fraxinus excelsior) to enlighten its impacts on biodiversity and other landscape functions of importance for the valley socio-economics. The study comprised an integrated assessment of land-use and land-cover change (LUCC) since the 1950s, and a scenario analysis of alternative future policy. We combined knowledge and methods from landscape ecology, land change and agricultural sciences, and a set of coordinated field studies to capture interactions and feedback in the local landscape/land-use system. Our results elicited the hierarchically-nested relationships between social and ecological processes. Agricultural change played a preeminent role in the spatial and temporal patterns of LUCC. Landscape colonisation by ash at the parcel level of organisation was merely controlled by grassland management, and in fact depended on the farmer's land management at the whole-farm level. LUCC patterns at the landscape level depended to a great extent on interactions between farm household behaviours and the spatial arrangement of landholdings within the landscape mosaic. Our results stressed the need to represent the local SES function at a fine scale to adequately capture scenarios of change in landscape functions. These findings orientated our modelling choices in the building an agent-based model for LUCC simulation (SMASH - Spatialized Multi-Agent System of landscape colonization by ASH). We discuss our method and results with reference to topical issues in interdisciplinary research into the sustainability of multifunctional landscapes

Control of hyperglycaemia in paediatric intensive care (CHiP): study protocol.

BACKGROUND: There is increasing evidence that tight blood glucose (BG) control improves outcomes in critically ill adults. Children show similar hyperglycaemic responses to surgery or critical illness. However it is not known whether tight control will benefit children given maturational differences and different disease spectrum. METHODS/DESIGN: The study is an randomised open trial with two parallel groups to assess whether, for children undergoing intensive care in the UK aged <or= 16 years who are ventilated, have an arterial line in-situ and are receiving vasoactive support following injury, major surgery or in association with critical illness in whom it is anticipated such treatment will be required to continue for at least 12 hours, tight control will increase the numbers of days alive and free of mechanical ventilation at 30 days, and lead to improvement in a range of complications associated with intensive care treatment and be cost effective. Children in the tight control group will receive insulin by intravenous infusion titrated to maintain BG between 4 and 7.0 mmol/l. Children in the control group will be treated according to a standard current approach to BG management. Children will be followed up to determine vital status and healthcare resources usage between discharge and 12 months post-randomisation. Information regarding overall health status, global neurological outcome, attention and behavioural status will be sought from a subgroup with traumatic brain injury (TBI). A difference of 2 days in the number of ventilator-free days within the first 30 days post-randomisation is considered clinically important. Conservatively assuming a standard deviation of a week across both trial arms, a type I error of 1% (2-sided test), and allowing for non-compliance, a total sample size of 1000 patients would have 90% power to detect this difference. To detect effect differences between cardiac and non-cardiac patients, a target sample size of 1500 is required. An economic evaluation will assess whether the costs of achieving tight BG control are justified by subsequent reductions in hospitalisation costs. DISCUSSION: The relevance of tight glycaemic control in this population needs to be assessed formally before being accepted into standard practice

Is the pharmacy profession innovative enough?: meeting the needs of Australian residents with chronic conditions and their carers using the nominal group technique

Background Community pharmacies are ideally located as a source of support for people with chronic conditions. Yet, we have limited insight into what innovative pharmacy services would support this consumer group to manage their condition/s. The aim of this study was to identify what innovations people with chronic conditions and their carers want from their ideal community pharmacy, and compare with what pharmacists and pharmacy support staff think consumers want. Methods We elicited ideas using the nominal group technique. Participants included people with chronic conditions, unpaid carers, pharmacists and pharmacy support staff, in four regions of Australia. Themes were identified via thematic analysis using the constant comparison method. Results Fifteen consumer/carer, four pharmacist and two pharmacy support staff groups were conducted. Two overarching themes were identified: extended scope of practice for the pharmacist and new or improved pharmacy services. The most innovative role for Australian pharmacists was medication continuance, within a limited time-frame. Consumers and carers wanted improved access to pharmacists, but this did not necessarily align with a faster or automated dispensing service. Other ideas included streamlined access to prescriptions via medication reminders, electronic prescriptions and a chronic illness card. Conclusions This study provides further support for extending the pharmacist’s role in medication continuance, particularly as it represents the consumer’s voice. How this is done, or the methods used, needs to optimise patient safety. A range of innovative strategies were proposed and Australian community pharmacies should advocate for and implement innovative approaches to improve access and ensure continuity of care

Protecting U.S. temporary waterways

International audienc

Phenotypic redshifts with self-organizing maps: A novel method to characterize redshift distributions of source galaxies for weak lensing

Wide-field imaging surveys such as the Dark Energy Survey (DES) rely on coarse measurements of spectral energy distributions in a few filters to estimate the redshift distribution of source galaxies. In this regime, sample variance, shot noise, and selection effects limit the attainable accuracy of redshift calibration and thus of cosmological constraints. We present a new method to combine wide-field, few-filter measurements with catalogs from deep fields with additional filters and sufficiently low photometric noise to break degeneracies in photometric redshifts. The multi-band deep field is used as an intermediary between wide-field observations and accurate redshifts, greatly reducing sample variance, shot noise, and selection effects. Our implementation of the method uses self-organizing maps to group galaxies into phenotypes based on their observed fluxes, and is tested using a mock DES catalog created from N-body simulations. It yields a typical uncertainty on the mean redshift in each of five tomographic bins for an idealized simulation of the DES Year 3 weak-lensing tomographic analysis of $\sigma_{\Delta z} = 0.007$, which is a 60% improvement compared to the Year 1 analysis. Although the implementation of the method is tailored to DES, its formalism can be applied to other large photometric surveys with a similar observing strategy.Comment: 24 pages, 11 figures; matches version accepted to MNRA