Observations of enhanced extreme ultraviolet continua during an X-class solar flare using SDO/EVE.

Observations of extreme ultraviolet (EUV) emission from an X-class solar flare that occurred on 2011 February 15 at 01: 44 UT are presented, obtained using the EUV Variability Experiment (EVE) on board the Solar Dynamics Observatory. The complete EVE spectral range covers the free-bound continua of H I (Lyman continuum), He I, and He II, with recombination edges at 91.2, 50.4, and 22.8 nm, respectively. By fitting the wavelength ranges blueward of each recombination edge with an exponential function, light curves of each of the integrated continua were generated over the course of the flare, as was emission from the free-free continuum (6.5-37 nm). The He II 30.4 nm and Ly alpha 121.6 nm lines, and soft X-ray (SXR; 0.1-0.8 nm) emission from GOES are also included for comparison. Each free-bound continuum was found to have a rapid rise phase at the flare onset similar to that seen in the 25-50 keV light curves from RHESSI, suggesting that they were formed by recombination with free electrons in the chromosphere. However, the free-free emission exhibited a slower rise phase seen also in the SXR emission from GOES, implying a predominantly coronal origin. By integrating over the entire flare the total energy emitted via each process was determined. We find that the flare energy in the EVE spectral range amounts to at most a few percent of the total flare energy, but EVE gives us a first comprehensive look at these diagnostically important continuum components.

Quantification of DNA damage by PFGE: development of an analytical approach to correct for the background distribution

Purpose: To analyse the currently existing methods to infer the extent of cellular DNA damage induced by ionizing radiation when the pulsed field gel electrophoresis (PFGE) technique is used.

Discovery of Main-Belt Comet P/2006 VW139 by Pan-STARRS 1

The main-belt asteroid (300163) 2006 VW139 (later designated P/2006 VW139) was discovered to exhibit comet-like activity by the Pan-STARRS1 (PS1) survey telescope using automated point-spread-function analyses performed by PS1's Moving Object Processing System. Deep follow-up observations show both a short (~10'') antisolar dust tail and a longer (~60'') dust trail aligned with the object's orbit plane, similar to the morphology observed for another main-belt comet (MBC), P/2010 R2 (La Sagra), and other well-established comets, implying the action of a long-lived, sublimation-driven emission event. Photometry showing the brightness of the near-nucleus coma remaining constant over ~30 days provides further evidence for this object's cometary nature, suggesting it is in fact an MBC, and not a disrupted asteroid. A spectroscopic search for CN emission was unsuccessful, though we find an upper limit CN production rate of Q CN 100 Myr, while a search for a potential asteroid family around the object reveals a cluster of 24 asteroids within a cutoff distance of 68 m s-1. At 70 m s-1, this cluster merges with the Themis family, suggesting that it could be similar to the Beagle family to which another MBC, 133P/Elst-Pizarro, belongs.

Cochrane review on 'Statins for the treatment of dementia'

OBJECTIVES: This review aimed to assess the clinical efficacy and tolerability of statins in the treatment of dementia. METHODS: We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group, The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS, as well as many trials registries and grey literature sources (27 October 2008). Double-blind, randomized controlled trials of statins given for at least 6?months in people with a diagnosis of dementia were included. Two independent authors extracted and assessed data independently against the inclusion criteria. Data were pooled where appropriate and entered into a meta-analysis. RESULTS: Three studies were identified (748 participants, age range 50-90?years). All patients had a diagnosis of probable or possible Alzheimer's disease according to standard criteria, and most patients were established on a cholinesterase inhibitor. Change in Alzheimer's Disease Assessment Scale cognitive subscale from baseline was a primary outcome in three studies; when data were pooled, statins did not provide any beneficial effect in this cognitive measure (mean difference -1.12; 95% confidence interval -3.99, 1.75; p?=?0.44). All studies provided a change in Mini-Mental State Examination from baseline; there was no significant benefit from statins in this cognitive measure when the data were pooled (mean difference -1.53; 95% confidence interval -3.28; 0.21, p?=?0.08). There were no studies identified assessing the role of statins in treatment of vascular dementia. There was no evidence that statins were detrimental to cognition. CONCLUSIONS: There is insufficient evidence to recommend statins for the treatment of dementia. Copyright © 2012 John Wiley & Sons, Ltd.

Steps to a better Belfast: physical activity assessment and promotion in primary care

BACKGROUND: Low physical activity (PA) levels which increase the risk of chronic disease are reported by two-thirds of the general UK population. Promotion of PA by primary healthcare professionals is advocated but more evidence is needed regarding effective ways of integrating this within everyday practice. This study aims to explore the feasibility of a randomised trial of a pedometer-based intervention, using step-count goals, recruiting patients from primary care. METHOD: Patients, aged 35-75, attending four practices in socioeconomically deprived areas, were invited to complete a General Practice PA Questionnaire during routine consultations. Health professionals invited 'inactive' individuals to a pedometer-based intervention and were randomly allocated to group 1 (prescribed a self-determined goal) or group 2 (prescribed a specific goal of 2500 steps/day above baseline). Both groups kept step-count diaries and received telephone follow-up at 1, 2, 6 and 11 weeks. Step counts were reassessed after 12 weeks. RESULTS: Of the 2154 patients attending, 192 questionnaires were completed (8.9%). Of these, 83 were classified as 'inactive'; 41(10 men; 31 women) completed baseline assessments, with the mean age of participants being 51 years. Mean baseline step counts were similar in group 1 (5685, SD 2945) and group 2 (6513, SD 3350). The mean increase in steps/day was greater in groups 1 than 2 ((2602, SD 1957) vs (748, SD 1997) p=0.005). CONCLUSIONS: A trial of a pedometer-based intervention using self-determined step counts appears feasible in primary care. Pedometers appear acceptable to women, particularly at a perimenopausal age, when it is important to engage in impact loading activities such as walking to maintain bone mineral density. An increase of 2500 steps/day is achievable for inactive patients, but the effectiveness of different approaches to realistic goal-setting warrants further study.

Identifying appropriate sampling and modelling approaches for analysing distributional patterns of Antarctic terrestrial arthropods along the Victoria Land latitudinal gradient

Biotic communities in Antarctic terrestrial ecosystems are relatively simple and often lack higher trophic levels (e. g. predators); thus, it is often assumed that species' distributions are mainly affected by abiotic factors such as climatic conditions, which change with increasing latitude, altitude and/or distance from the coast. However, it is becoming increasingly apparent that factors other than geographical gradients affect the distribution of organisms with low dispersal capability such as the terrestrial arthropods. In Victoria Land (East Antarctica) the distribution of springtail (Collembola) and mite (Acari) species vary at scales that range from a few square centimetres to regional and continental. Different species show different scales of variation that relate to factors such as local geological and glaciological history, and biotic interactions, but only weakly with latitudinal/altitudinal gradients. Here, we review the relevant literature and outline more appropriate sampling designs as well as suitable modelling techniques (e. g. linear mixed models and eigenvector mapping), that will more adequately address and identify the range of factors responsible for the distribution of terrestrial arthropods in Antarctica.

An inherited duplication at the gene p21 Protein-Activated Kinase 7 (PAK7) is a risk factor for psychosis

Identifying rare, highly penetrant risk mutations may be an important step in dissecting the molecular etiology of schizophrenia. We conducted a gene-based analysis of large (>100kb), rare copy number variants (CNVs) in the Wellcome Trust Case Control Consortium 2 (WTCCC2) schizophrenia sample of 1,564 cases and 1,748 controls all from Ireland, and further extended the analysis to include an additional 5,196 UK controls. We found association with duplications at chr20p12.2 (P=0.007) and evidence of replication in large independent European schizophrenia (P=0.052) and UK bipolar disorder case-control cohorts (P=0.047). A combined analysis of Irish/UK subjects including additional psychosis cases (schizophrenia and bipolar disorder) identified 22 carriers in 11,707 cases and 10 carriers in 21,204 controls (meta-analysis CMH P value=2x10(-4) (odds ratio (OR)=11.3, 95% CI=3.7, ∞)). Nineteen of the 22 cases and 8 of the 10 controls carried duplications starting at 9.68Mb with similar breakpoints across samples. By haplotype analysis and sequencing we identified a tandem ∼149kb duplication overlapping the gene p21 Protein-Activated Kinase 7 (PAK7, also called PAK5) which was in linkage disequilibrium with local haplotypes (P=2.5x10(-21)), indicative of a single ancestral duplication event. We confirmed the breakpoints in 8/8 carriers tested and found co-segregation of the duplication with illness in two additional family members of one of the affected probands. We demonstrate that PAK7 is developmentally co-expressed with another known psychosis risk gene (DISC1) suggesting a potential molecular mechanism involving aberrant synapse development and plasticity.

The influence of parents, older siblings, and non-parental care on infant development at nine months of age

Background: The majority of research examining the influence of social environment on early child development suggests benefits to two-parent households, but contradictory evidence for the effects of siblings. The aims of the present study were to examine the influence of the child's proximal social environment, and the effects of interactions between socioeconomic status and social environment on developmental outcomes.

Methods: Primary caregivers of a representative sample of 10,748 nine-month-old infants in Ireland completed the Ages and Stages Questionnaire and provided information on social environment. Adjustment was made for infant and maternal characteristics, household income, and area where the child was living at the time of the study. Further analyses tested for interactions between social environment and household income.

Results: Binary logistic regressions indicated no effects for number of parents in the household. However, the presence of siblings in the household was a consistent predictor of failing to reach milestones in communication, gross motor, problem-solving, and personal-social development. Furthermore, there was a gradient of increasing likelihood of failing in gross motor, problem-solving, and personal-social development with increasing numbers of siblings. Care by a grandparent decreased the likelihood of failing in communication and personal-social development.

Conclusions:These findings do not support the majority of research that finds positive benefits for two-parent households. Similarly, the findings suggest limited effects for non-parental care. However, the observed negative effects of siblings support both the confluence and resource dilution models of sibling effect. Examination of follow-up data may elucidate current findings.

Is there a common water-activity limit for the three domains of life?

Archaea and Bacteria constitute a majority of life systems on Earth but have long been considered inferior to Eukarya in terms of solute tolerance. Whereas the most halophilic prokaryotes are known for an ability to multiply at saturated NaCl (water activity (a_w) 0.755) some xerophilic fungi can germinate, usually at high-sugar concentrations, at values as low as 0.650–0.605 a_w. Here, we present evidence that halophilic prokayotes can grow down to water activities of <0.755 for Halanaerobium lacusrosei (0.748), Halobacterium strain 004.1 (0.728), Halobacterium sp. NRC-1 and Halococcus morrhuae (0.717), Haloquadratum walsbyi (0.709), Halococcus salifodinae (0.693), Halobacterium noricense (0.687), Natrinema pallidum (0.681) and haloarchaeal strains GN-2 and GN-5 (0.635 a_w). Furthermore, extrapolation of growth curves (prone to giving conservative estimates) indicated theoretical minima down to 0.611 a_w for extreme, obligately halophilic Archaea and Bacteria. These were compared with minima for the most solute-tolerant Bacteria in high-sugar (or other non-saline) media (Mycobacterium spp., Tetragenococcus halophilus, Saccharibacter floricola, Staphylococcus aureus and so on) and eukaryotic microbes in saline (Wallemia spp., Basipetospora halophila, Dunaliella spp. and so on) and high-sugar substrates (for example, Xeromyces bisporus, Zygosaccharomyces rouxii, Aspergillus and Eurotium spp.). We also manipulated the balance of chaotropic and kosmotropic stressors for the extreme, xerophilic fungi Aspergillus penicilloides and X. bisporus and, via this approach, their established water-activity limits for mycelial growth (~0.65) were reduced to 0.640. Furthermore, extrapolations indicated theoretical limits of 0.632 and 0.636 a_w for A. penicilloides and X. bisporus, respectively. Collectively, these findings suggest that there is a common water-activity limit that is determined by physicochemical constraints for the three domains of life.

Microstructure and dielectric properties of epitaxial BaTiO3 films and BaTiO3/SrTiO3 multilayers

Epitaxial BaTiO3 films and BaTiO3/SrTiO3 multilayers were grown by pulsed laser deposition (PLD) on (001)-oriented Nb-doped SrTiO3 (SrTiO3:Nb) substrates. Measurements of the dielectric properties were performed comparing BaTiO3 films and BaTiO3/SrTiO3 multilayers of different number of individual layers, but equal overall thickness. The dielectric loss saturates for a thickness above 300 nm, and linearly decreases with decreasing film thickness below a thickness of 75 nm, and it is independent on the number of multilayers, pointing to some interface effect. The thickness dependence of the dielectric constant of BaTiO3 films and BaTiO3/SrTiO3 multilayers; exhibits a change in the linear slope at a thickness of 75 nm. This behavior is explained by the change observed in the morphology at a thickness of 75 nm. In order to explain the thickness dependence of the dielectric constant, two approaches are considered in this paper, viz. a "series capacitor" model and a "dead layer" model.

A Continuous Time Markov Chain Based Sequential Analytical Approach for Composite Power System Reliability Assessment

This paper proposes a continuous time Markov chain (CTMC) based sequential analytical approach for composite generation and transmission systems reliability assessment. The basic idea is to construct a CTMC model for the composite system. Based on this model, sequential analyses are performed. Various kinds of reliability indices can be obtained, including expectation, variance, frequency, duration and probability distribution. In order to reduce the dimension of the state space, traditional CTMC modeling approach is modified by merging all high order contingencies into a single state, which can be calculated by Monte Carlo simulation (MCS). Then a state mergence technique is developed to integrate all normal states to further reduce the dimension of the CTMC model. Moreover, a time discretization method is presented for the CTMC model calculation. Case studies are performed on the RBTS and a modified IEEE 300-bus test system. The results indicate that sequential reliability assessment can be performed by the proposed approach. Comparing with the traditional sequential Monte Carlo simulation method, the proposed method is more efficient, especially in small scale or very reliable power systems.

Novel functional interaction between the plasma membrane Ca2+ pump 4b and the proapoptotic tumor suppressor Ras-associated factor 1 (RASSF1)

Plasma membrane calmodulin-dependent calcium ATPases (PMCAs) are enzymatic systems implicated in the extrusion of calcium from the cell. We and others have previously identified molecular interactions between the cytoplasmic COOH-terminal end of PMCA and PDZ domain-containing proteins. These interactions suggested a new role for PMCA as a modulator of signal transduction pathways. The existence of other intracellular regions in the PMCA molecule prompted us to investigate the possible participation of other domains in interactions with different partner proteins. A two-hybrid screen of a human fetal heart cDNA library, using the region 652-840 of human PMCA4b (located in the catalytic, second intracellular loop) as bait, revealed a novel interaction between PMCA4b and the tumor suppressor RASSF1, a Ras effector protein involved in H-Ras-mediated apoptosis. Immunofluorescence co-localization, immunoprecipitation, and glutathione S-transferase pull-down experiments performed in mammalian cells provided further confirmation of the physical interaction between the two proteins. The interaction domain has been narrowed down to region 74-123 of RASSF1C (144-193 in RASSF1A) and 652-748 of human PMCA4b. The functionality of this interaction was demonstrated by the inhibition of the epidermal growth factor-dependent activation of the Erk pathway when PMCA4b and RASSF1 were co-expressed. This inhibition was abolished by blocking PMCA/RASSSF1 association with an excess of a green fluorescent protein fusion protein containing the region 50-123 of RASSF1C. This work describes a novel protein-protein interaction involving a domain of PMCA other than the COOH terminus. It suggests a function for PMCA4b as an organizer of macromolecular protein complexes, where PMCA4b could recruit diverse proteins through interaction with different domains. Furthermore, the functional association with RASSF1 indicates a role for PMCA4b in the modulation of Ras-mediated signaling.

Comorbidity in severe asthma requiring systemic corticosteroid therapy: cross-sectional data from the Optimum Patient Care Research Database and the British Thoracic Difficult Asthma Registry

Objective: To determine the prevalence of systemic corticosteroid-induced morbidity in severe asthma.
Design: Cross-sectional observational study.Setting The primary care Optimum Patient Care Research Database and the British Thoracic Society Difficult Asthma Registry.
Participants: Optimum Patient Care Research Database (7195 subjects in three age- and gender-matched groups)—severe asthma (Global Initiative for Asthma (GINA) treatment step 5 with four or more prescriptions/year of oral corticosteroids, n=808), mild/moderate asthma (GINA treatment step 2/3, n=3975) and non-asthma controls (n=2412). 770 subjects with severe asthma from the British Thoracic Society Difficult Asthma Registry (442 receiving daily oral corticosteroids to maintain disease control).
Main outcome measures: Prevalence rates of morbidities associated with systemic steroid exposure were evaluated and reported separately for each group.
Results: 748/808 (93%) subjects with severe asthma had one or more condition linked to systemic corticosteroid exposure (mild/moderate asthma 3109/3975 (78%), non-asthma controls 1548/2412 (64%); p<0.001 for severe asthma versus non-asthma controls). Compared with mild/moderate asthma, morbidity rates for severe asthma were significantly higher for conditions associated with systemic steroid exposure (type II diabetes 10% vs 7%, OR=1.46 (95% CI 1.11 to 1.91), p<0.01; osteoporosis 16% vs 4%, OR=5.23, (95% CI 3.97 to 6.89), p<0.001; dyspeptic disorders (including gastric/duodenal ulceration) 65% vs 34%, OR=3.99, (95% CI 3.37 to 4.72), p<0.001; cataracts 9% vs 5%, OR=1.89, (95% CI 1.39 to 2.56), p<0.001). In the British Thoracic Society Difficult Asthma Registry similar prevalence rates were found, although, additionally, high rates of osteopenia (35%) and obstructive sleep apnoea (11%) were identified.

Conclusions: Oral corticosteroid-related adverse events are common in severe asthma. New treatments which reduce exposure to oral corticosteroids may reduce the prevalence of these conditions and this should be considered in cost-effectiveness analyses of these new treatments.

Potentially inappropriate prescribing in two populations with differing socio-economic profiles: a cross-sectional database study using the PROMPT criteria

PURPOSE: The purpose of this study is to establish the prevalence of potentially inappropriate prescribing (PIP) in middle-aged adults (45-64 years) in two populations with differing socio-economic profiles, and to investigate factors associated with PIP, using the PROMPT (PRescribing Optimally in Middle-aged People's Treatments) criteria.METHODS: A retrospective cross-sectional study was conducted using 2012 data from the Enhanced Prescribing Database (EPD), covering the full population in Northern Ireland and the Health Services Executive Primary Care Reimbursement Service (HSE-PCRS) database, covering the most socio-economically deprived third of the population in this age group in the Republic of Ireland. The prevalence for each PROMPT criterion and overall prevalence of PIP were calculated. Logistic regression was used to investigate the association between PIP and gender, age group and polypharmacy.RESULTS: This study included 441,925 patients from the EPD and 309,748 patients from the HSE-PCRS database. Polypharmacy was common in both datasets (46.7 % in the HSE-PCRS and 20.3 % in the EPD). The prevalence of PIP was 42.9 % (95%CI 42.7, 43.1) in the HSE-PCRS and 21.1 % (95%CI 21.0, 21.2) in the EPD. Age group, female gender and polypharmacy were significantly associated with PIP in both populations (p < 0.05) and polypharmacy had the strongest association.CONCLUSIONS: PIP is common amongst middle-aged people with the risk of PIP increasing with polypharmacy. Differences in the prevalence of polypharmacy and PIP between the two populations may relate to heterogeneity in healthcare services and different socio-economic profiles, with higher rates of multimorbidity and associated polypharmacy in more deprived groups.