Stochastic density functional theory

Linear-scaling implementations of density functional theory (DFT) reach their intended efficiency regime only when applied to systems having a physical size larger than the range of their Kohn-Sham density matrix (DM). This causes a problem since many types of large systems of interest have a rather broad DM range and are therefore not amenable to analysis using DFT methods. For this reason, the recently proposed stochastic DFT (sDFT), avoiding exhaustive DM evaluations, is emerging as an attractive alternative linear-scaling approach. This review develops a general formulation of sDFT in terms of a (non)orthogonal basis representation and offers an analysis of the statistical errors (SEs) involved in the calculation. Using a new Gaussian-type basis-set implementation of sDFT, applied to water clusters and silicon nanocrystals, it demonstrates and explains how the standard deviation and the bias depend on the sampling rate and the system size in various types of calculations. We also develop basis-set embedded-fragments theory, demonstrating its utility for reducing the SEs for energy, density of states and nuclear force calculations. Finally, we discuss the algorithmic complexity of sDFT, showing it has CPU wall-time linear-scaling. The method parallelizes well over distributed processors with good scalability and therefore may find use in the upcoming exascale computing architectures

Dehydration accelerates reductions in cerebral blood flow during prolonged exercise in the heat without compromising brain metabolism

Dehydration hastens the decline in cerebral blood flow (CBF) during incremental exercise, while the cerebral metabolic rate for oxygen (CMRO2) is preserved. It remains unknown whether CMRO2 is also maintained during prolonged exercise in the heat and whether an eventual decline in CBF is coupled to fatigue. Two studies were undertaken. In study 1, ten male cyclists cycled in the heat for ~2 h with (control) and without fluid replacement (dehydration) while internal (ICA) and external (ECA) carotid artery blood flow and core and blood temperature were obtained. Arterial and internal jugular venous blood samples were assessed with dehydration to evaluate the CMRO2. In study 2 (8 males), middle cerebral artery blood velocity (MCA Vmean) was measured during prolonged exercise to exhaustion in both dehydrated and euhydrated states. After a rise at the onset of exercise, ICA flow declined to baseline with progressive dehydration (P < 0.05). However, cerebral metabolism remained stable through enhanced oxygen and glucose extraction (P < 0.05). ECA flow increased for one hour but declined prior to exhaustion. Fluid ingestion maintained cerebral and extra-cranial perfusion throughout non-fatiguing exercise. During exhaustive exercise, however, euhydration delayed but did not prevent the decline in cerebral perfusion. In conclusion, during prolonged exercise in the heat dehydration accelerates the decline in CBF without affecting CMRO2 and also restricts extra-cranial perfusion. Thus fatigue is related to reduction in CBF and extra-cranial perfusion rather than in CMRO2.The study was supported by a grant from the Gatorade Sports Science Institute, PepsiCo Inc, USA

Personalized copy number and segmental duplication maps using next-generation sequencing

Despite their importance in gene innovation and phenotypic variation, duplicated regions have remained largely intractable owing to difficulties in accurately resolving their structure, copy number and sequence content. We present an algorithm (mrFAST) to comprehensively map next-generation sequence reads, which allows for the prediction of absolute copy-number variation of duplicated segments and genes. We examine three human genomes and experimentally validate genome-wide copy number differences. We estimate that, on average, 73-87 genes vary in copy number between any two individuals and find that these genic differences overwhelmingly correspond to segmental duplications (odds ratio = 135; P < 2.2 x 10(-16)). Our method can distinguish between different copies of highly identical genes, providing a more accurate assessment of gene content and insight into functional constraint without the limitations of array-based technology

Use of a formal consensus development technique to produce recommendations for improving the effectiveness of adult mental health multidisciplinary team meetings

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Multidisciplinary team (MDT) meetings are the core mechanism for delivering mental health care but it is unclear which models improve care quality. The aim of the study was to agree recommendations for improving the effectiveness of adult mental health MDT meetings, based on national guidance, research evidence and experiential insights from mental health and other medical specialties. METHODS: We established an expert panel of 16 health care professionals, policy-makers and patient representatives. Five panellists had experience in a range of adult mental health services, five in heart failure services and six in cancer services. Panellists privately rated 68 potential recommendations on a scale of one to nine, and re-rated them after panel discussion using the RAND/UCLA Appropriateness Method to determine consensus. RESULTS: We obtained agreement (median ≥ 7) and low variation in extent of agreement (Mean Absolute Deviation from Median of ≤1.11) for 21 recommendations. These included the explicit agreement and auditing of MDT meeting objectives, and the documentation and monitoring of treatment plan implementation. CONCLUSIONS: Formal consensus development methods that involved learning across specialities led to feasible recommendations for improved MDT meeting effectiveness in a wide range of settings. Our findings may be used by adult mental health teams to reflect on their practice and facilitate improvement. In some other contexts, the recommendations will require modification. For example, in Child and Adolescent Mental Health Services, context-specific issues such as the role of carers should be taken into account. A limitation of the comparative approach adopted was that only five members of the panel of 16 experts were mental health specialists.This report presents independent research commissioned by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, MRC, CCF, NETSCC, the Health Services and Delivery Research programme or the Department of Health

Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD:implication for COPD-associated neuropathogenesis

The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD

Determinants of treatment plan implementation in multidisciplinary team meetings for patients with chronic diseases: a mixed-methods study.

This is the final version of the article. Available from the publisher via the DOI in this record.OBJECTIVE: Multidisciplinary team (MDT) meetings are assumed to produce better decisions and are extensively used to manage chronic disease in the National Health Service (NHS). However, evidence for their effectiveness is mixed. Our objective was to investigate determinants of MDT effectiveness by examining factors influencing the implementation of MDT treatment plans. This is a proxy measure of effectiveness, because it lies on the pathway to improvements in health, and reflects team decision making which has taken account of clinical and non-clinical information. Additionally, this measure can be compared across MDTs for different conditions. METHODS: We undertook a prospective mixed-methods study of 12 MDTs in London and North Thames. Data were collected by observation of 370 MDT meetings, interviews with 53 MDT members, and from 2654 patient medical records. We examined the influence of patient-related factors (disease, age, sex, deprivation, whether their preferences and other clinical/health behaviours were mentioned) and MDT features (as measured using the 'Team Climate Inventory' and skill mix) on the implementation of MDT treatment plans. RESULTS: The adjusted odds (or likelihood) of implementation was reduced by 25% for each additional professional group represented at the MDT meeting. Implementation was more likely in MDTs with clear goals and processes and a good 'Team Climate' (adjusted OR 1.96; 95% CI 1.15 to 3.31 for a unit increase in Team Climate Inventory (TCI) score). Implementation varied by disease category, with the lowest adjusted odds of implementation in mental health teams. Implementation was also lower for patients living in more deprived areas (adjusted odds of implementation for patients in the most compared with least deprived areas was 0.60, 95% CI 0.39 to 0.91). CONCLUSIONS: Greater multidisciplinarity is not necessarily associated with more effective decision making. Explicit goals and procedures are also crucial. Decision implementation should be routinely monitored to ensure the equitable provision of care.This project was funded by the NIHR Health Services and Delivery Research programme (project number 09/2001/ 04) and will be published in full in the Health Services and Delivery Research Journal. Further information available at: (http://www.netscc.ac.uk/hsdr/projdetails.php?ref=09-2001-04). In accordance with NIHR regulations, the findings reported here are to be referred to as initial until the NIHR final report has been published. The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, the writing of the report, or the decision to submit the report for publication

Retained Surgical Items and Minimally Invasive Surgery

A retained surgical item is a surgical patient safety problem. Early reports have focused on the epidemiology of retained-item cases and the identification of patient risk factors for retention. We now know that retention has very little to do with patient characteristics and everything to do with operating room culture. It is a perception that minimally invasive procedures are safer with regard to the risk of retention. Minimally invasive surgery is still an operation where an incision is made and surgical tools are placed inside of patients, so these cases are not immune to the problem of inadvertent retention. Retained surgical items occur because of problems with multi-stakeholder operating room practices and problems in communication. The prevention of retained surgical items will therefore require practice change, knowledge, and shared information between all perioperative personnel

Incorporating psychology into cyber security education: A pedagogical approach

The role of the human in cyber security is well acknowledged. Many cyber security incidents rely upon targets performing specific behavioural actions, such as opening a link within a phishing email. Cyber adversaries themselves are driven by psychological processes such as motivation, group dynamics and social identity. Furthermore, both intentional and unintentional insider threats are associated with a range of psychological factors, including cognitive load, mental wellbeing, trust and interpersonal relations. By incorporating psychology into cyber security education, practitioners will be better equipped with the skills they need to address cyber security issues. However, there are challenges in doing so. Psychology is a broad discipline, and many theories, approaches and methods may have little practical significance to cyber security. There is a need to sift through the literature to identify what can be applied to cyber security. There are also pedagogical differences in how psychology and cyber security are taught and also psychological differences in the types of student that may typically study psychology and cyber security. To engage with cyber security students, it is important that these differences are identified and positively addressed. Essential to this endeavor is the need to discuss and collaborate across the two disciplines. In this paper, we explore these issues and discuss our experiences as psychology and cyber security academics who work across disciplines to deliver psychology education to cyber security students, practitioners and commercial clients

Protecting Endangered Species: Do the Main Legislative Tools Work?

It is critical to assess the effectiveness of the tools used to protect endangered species. The main tools enabled under the U.S. Endangered Species Act (ESA) to promote species recovery are funding, recovery plan development and critical habitat designation. Earlier studies sometimes found that statistically significant effects of these tools could be detected, but they have not answered the question of whether the effects were large enough to be biologically meaningful. Here, we ask: how much does the recovery status of ESA-listed species improve with the application of these tools? We used species' staus reports to Congress from 1988 to 2006 to quantify two measures of recovery for 1179 species. We related these to the amount of federal funding, years with a recovery plan, years with critical habitat designation, the amount of peer-reviewed scientific information, and time listed. We found that change in recovery status of listed species was, at best, only very weakly related to any of these tools. Recovery was positively related to the number of years listed, years with a recovery plan, and funding, however, these tools combined explain <13% of the variation in recovery status among species. Earlier studies that reported significant effects of these tools did not focus on effect sizes; however, they are in fact similarly small. One must conclude either that these tools are not very effective in promoting species' recovery, or (as we suspect) that species recovery data are so poor that it is impossible to tell whether the tools are effective or not. It is critically important to assess the effectiveness of tools used to promote species recovery; it is therefore also critically important to obtain population status data that are adequate to that task

An ancient and conserved function for armadillo-related proteins in the control of spore and seed germination by abscisic acid

Armadillo‐related proteins regulate development throughout eukaryotic kingdoms. In the flowering plant Arabidopsis thaliana, Armadillo‐related ARABIDILLO proteins promote multicellular root branching. ARABIDILLO homologues exist throughout land plants, including early‐diverging species lacking true roots, suggesting that early‐evolving ARABIDILLOs had additional biological roles. Here we investigated, using molecular genetics, the conservation and diversification of ARABIDILLO protein function in plants separated by c. 450 million years of evolution. We demonstrate that ARABIDILLO homologues in the moss Physcomitrella patens regulate a previously undiscovered inhibitory effect of abscisic acid (ABA) on spore germination. Furthermore, we show that A. thaliana ARABIDILLOs function similarly during seed germination. Early‐diverging ARABIDILLO homologues from both P. patens and the lycophyte Selaginella moellendorffii can substitute for ARABIDILLO function during A. thaliana root development and seed germination. We conclude that (1) ABA was co‐opted early in plant evolution to regulate functionally analogous processes in spore‐ and seed‐producing plants and (2) plant ARABIDILLO germination functions were co‐opted early into both gametophyte and sporophyte, with a specific rooting function evolving later in the land plant lineage