Expanding the Lorentz concept in magnetism

This is the final version. Available on open access from IOP Publishing via the DOI in this recordIn 1878, the Dutch physicist Hendrik Antoon Lorentz first addressed the calculation of the local electric field at an atomic site in a ferroelectric material, generated by all the other electric dipoles within the sample. This calculation, which applies equally well to ferromagnets, is taught in Universities around the World. Here we demonstrate that the Lorentz concept can be used to speed up calculations of the local dipolar field in square, circular, and elliptical shaped monolayers and thin films, not only at the center of the film, but across the sample. Calculations show that long elliptical and rectangular films should exhibit the narrowest ferromagnetic resonance (FMR) linewidth. In addition, discrete dipole calculations show that the Lorentz cavity field $\left({\mu }_{0}M/3\right)$ does not hold in tetragonal films. Depending on the ratio (b/a), the local field can be either less/greater than $\left({\mu }_{0}M/3\right):$ an observation that has implications for FMR. 3D simple cubic (SC) systems are also examined. For example, while most texts discuss the Lorentz cavity field in terms of a Lorentz sphere, the Lorentz cavity field still holds when a Lorentz sphere is replaced by a the Lorentz cube, but only in cubic SC, FCC and BCC systems. Finally, while the primary emphasis is on the discrete dipole–dipole interaction, contact is made with the continuum model. For example, in the continuous SC dipole model, just one monolayer is required to generate the Lorentz cavity field. This is in marked contrast to the discrete dipole model, where a minimum of five adjacent monolayers is required.Engineering and Physical Sciences Research Council (EPSRC

High-threshold mechanosensitive ion channels blocked by a novel conopeptide mediate pressure-evoked pain

Little is known about the molecular basis of somatosensory mechanotransduction in mammals. We screened a library of peptide toxins for effects on mechanically activated currents in cultured dorsal root ganglion neurons. One conopeptide analogue, termed NMB-1 for noxious mechanosensation blocker 1, selectively inhibits (IC50 1 µM) sustained mechanically activated currents in a subset of sensory neurons. Biotinylated NMB-1 retains activity and binds selectively to peripherin-positive nociceptive sensory neurons. The selectivity of NMB-1 was confirmed by the fact that it has no inhibitory effects on voltage-gated sodium and calcium channels, or ligand-gated channels such as acid-sensing ion channels or TRPA1 channels. Conversely, the tarantula toxin, GsMTx-4, which inhibits stretch-activated ion channels, had no effects on mechanically activated currents in sensory neurons. In behavioral assays, NMB-1 inhibits responses only to high intensity, painful mechanical stimulation and has no effects on low intensity mechanical stimulation or thermosensation. Unexpectedly, NMB-1 was found to also be an inhibitor of rapid FM1-43 loading (a measure of mechanotransduction) in cochlear hair cells. These data demonstrate that pharmacologically distinct channels respond to distinct types of mechanical stimuli and suggest that mechanically activated sustained currents underlie noxious mechanosensation. NMB-1 thus provides a novel diagnostic tool for the molecular definition of channels involved in hearing and pressure-evoked pain

Allowing for missing outcome data and incomplete uptake of randomised interventions, with application to an Internet-based alcohol trial

Missing outcome data and incomplete uptake of randomised interventions are common problems, which complicate the analysis and interpretation of randomised controlled trials, and are rarely addressed well in practice. To promote the implementation of recent methodological developments, we describe sequences of randomisation-based analyses that can be used to explore both issues. We illustrate these in an Internet-based trial evaluating the use of a new interactive website for those seeking help to reduce their alcohol consumption, in which the primary outcome was available for less than half of the participants and uptake of the intervention was limited

Self-Affirmation Improves Problem-Solving under Stress

High levels of acute and chronic stress are known to impair problem-solving and creativity on a broad range of tasks. Despite this evidence, we know little about protective factors for mitigating the deleterious effects of stress on problem-solving. Building on previous research showing that self-affirmation can buffer stress, we tested whether an experimental manipulation of self-affirmation improves problem-solving performance in chronically stressed participants. Eighty undergraduates indicated their perceived chronic stress over the previous month and were randomly assigned to either a self-affirmation or control condition. They then completed 30 difficult remote associate problem-solving items under time pressure in front of an evaluator. Results showed that self-affirmation improved problem-solving performance in underperforming chronically stressed individuals. This research suggests a novel means for boosting problem-solving under stress and may have important implications for understanding how self-affirmation boosts academic achievement in school settings. © 2013 Creswell et al

Confirmation of childhood acute lymphoblastic leukemia variants, ARID5B and IKZF1, and interaction with parental environmental exposures.

Genome wide association studies (GWAS) have established association of ARID5B and IKZF1 variants with childhood acute lymphoblastic leukemia (ALL). Epidemiological studies suggest that environmental factors alone appear to make a relatively minor contribution to disease risk. The polygenic nature of childhood ALL predisposition together with the timing of environmental triggers may hold vital clues for disease etiology. This study presents results from an Australian GWAS of childhood ALL cases (n = 358) and population controls (n = 1192). Furthermore, we utilised family trio (n = 204) genotypes to extend our investigation to gene-environment interaction of significant loci with parental exposures before conception, and child's sex and age. Thirteen SNPs achieved genome wide significance in the population based case/control analysis; ten annotated to ARID5B and three to IKZF1. The most significant SNPs in these regions were ARID5B rs4245595 (OR 1.63, CI 1.38-1.93, P = 2.13×10(-9)), and IKZF1 rs1110701 (OR 1.69, CI 1.42-2.02, p = 7.26×10(-9)). There was evidence of gene-environment interaction for risk genotype at IKZF1, whereby an apparently stronger genetic effect was observed if the mother took folic acid or if the father did not smoke prior to pregnancy (respective interaction P-values: 0.04, 0.05). There were no interactions of risk genotypes with age or sex (P-values >0.2). Our results evidence that interaction of genetic variants and environmental exposures may further alter risk of childhood ALL however, investigation in a larger population is required. If interaction of folic acid supplementation and IKZF1 variants holds, it may be useful to quantify folate levels prior to initiating use of folic acid supplements

Possible effect of medically administered antibiotics on the mutans streptococci: implications for reduction in decay

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74585/1/j.1399-302X.1989.tb00103.x.pd

Patient-reported GP health assessments rather than individual cardiovascular risk burden are associated with the engagement in lifestyle changes: Population-based survey in South Australia

© 2019 The Author(s). Background: Little is known about whether a more comprehensive health assessment, performed by a general practitioner (GP) during a clinical encounter, could influence patients' lifestyle. We aimed to investigate whether health assessments, performed by GPs, are more important than the presence of cardiovascular disease (CVD) or cardiometabolic risk factors (obesity, diabetes, hypertension, dyslipidaemia) for engagement in lifestyle change. Methods: Cross-sectional, population-based survey conducted in South Australia (September-December 2017) using face-To-face interviews and self-reported data of 2977 individuals aged 15+ years. The main outcome was engagement in four lifestyle changes: 1) increasing fruit/vegetable intake, 2) increasing physical activity level, 3) reducing alcohol consumption, and 4) attempts to stop smoking. Health assessments performed by a GP in the last 12 months included clinical/laboratory investigations (weight/waist circumference, blood pressure, glucose levels, lipid levels) and questions about lifestyle/wellbeing (current diet, physical activity, smoking status, alcohol intake, mental health, sleeping problems). Results were restricted to individuals aged 35+ years because of the low prevalence of CVD or their risk factors among younger participants. Logistic regression was used in all associations, adjusted for sociodemographic, lifestyle, mental health, and clinical variables. Results: Of the 2384 investigated adults (mean age 57.3 ± 13.9 years; 51.9% females), 10.2% had CVD and 49.1% at least one cardiometabolic risk factor. Clinical/laboratory assessments performed by the GP were 2-3 times more frequent than assessments of lifestyle, mental health status, or sleeping problems, especially among those with CVD. Individuals with CVD or a cardiometabolic risk factor were no more likely to be increasing their fruit/vegetable consumption (33.6%), physical activity level (40.9%), reducing alcohol consumption (31.1%), or trying to quit smoking (34.0%) than 'healthy' participants. However, lifestyle changes were between 30 and 100% more likely when GPs performed three or more health assessments (either clinical/laboratory or questions about lifestyle/wellbeing) than when individuals did not visit the GP or when GPs performed no any assessment during these clinical encounters (p < 0.05 in all cases). Conclusion: More frequent and comprehensive CVD-related assessments by GPs were more important in promoting a healthier lifestyle than the presence of CVD or cardiometabolic risk factors by themselves

Aripiprazole in the Maintenance Treatment of Bipolar Disorder: A Critical Review of the Evidence and Its Dissemination into the Scientific Literature

A systematic search of the literature reveals limited evidence to support use of aripiprazole, a second-generation antipsychotic medication, in maintenance therapy of bipolar disorder, despite widespread use

Trends in the availability of the vulture-toxic drug, diclofenac, and other NSAIDs in South Asia, as revealed by covert pharmacy surveys

SummaryThe catastrophic declines of three species of ‘Critically Endangered’ Gyps vultures in South Asia were caused by unintentional poisoning by the non-steroidal anti-inflammatory drug (NSAID) diclofenac. Despite a ban on its veterinary use in 2006 (India, Nepal, Pakistan) and 2010 (Bangladesh), residues of diclofenac have continued to be found in cattle carcasses and in dead wild vultures. Another NSAID, meloxicam, has been shown to be safe to vultures. From 2012 to 2018, we undertook covert surveys of pharmacies in India, Nepal and Bangladesh to investigate the availability and prevalence of NSAIDs for the treatment of livestock. The purpose of the study was to establish whether diclofenac continued to be sold for veterinary use, whether the availability of meloxicam had increased and to determine which other veterinary NSAIDs were available. The availability of diclofenac declined in all three countries, virtually disappearing from pharmacies in Nepal and Bangladesh, highlighting the advances made in these two countries to reduce this threat to vultures. In India, diclofenac still accounted for 10–46% of all NSAIDs offered for sale for livestock treatment in 2017, suggesting weak enforcement of existing regulations and a continued high risk to vultures. Availability of meloxicam increased in all countries and was the most common veterinary NSAID in Nepal (89.9% in 2017). Although the most widely available NSAID in India in 2017, meloxicam accounted for only 32% of products offered for sale. In Bangladesh, meloxicam was less commonly available than the vulture-toxic NSAID ketoprofen (28% and 66%, respectively, in 2018), despite the partial government ban on ketoprofen in 2016. Eleven different NSAIDs were recorded, several of which are known or suspected to be toxic to vultures. Conservation priorities should include awareness raising, stricter implementation of current bans, bans on other vulture-toxic veterinary NSAIDs, especially aceclofenac and nimesulide, and safety-testing of other NSAIDs on Gyps vultures to identify safe and toxic drugs.</jats:p

Buffy coat specimens remain viable as a DNA source for highly multiplexed genome-wide genetic tests after long term storage

<p>Abstract</p> <p>Background</p> <p>Blood specimen collection at an early study visit is often included in observational studies or clinical trials for analysis of secondary outcome biomarkers. A common protocol is to store buffy coat specimens for future DNA isolation and these may remain in frozen storage for many years. It is uncertain if the DNA remains suitable for modern genome wide association (GWA) genotyping.</p> <p>Methods</p> <p>We isolated DNA from 120 Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial buffy coats sampling a range of storage times up to 9 years and other factors that could influence DNA yield. We performed TaqMan SNP and GWA genotyping to test whether the DNA retained integrity for high quality genetic analysis.</p> <p>Results</p> <p>We tested two QIAGEN automated protocols for DNA isolation, preferring the Compromised Blood Protocol despite similar yields. We isolated DNA from all 120 specimens (yield range 1.1-312 ug per 8.5 ml ACD tube of whole blood) with only 3/120 samples yielding < 10 ug DNA. Age of participant at blood draw was negatively associated with yield (mean change -2.1 ug/year). DNA quality was very good based on gel electrophoresis QC, TaqMan genotyping of 6 SNPs (genotyping no-call rate 1.1% in 702 genotypes), and excellent quality GWA genotyping data (maximum per sample genotype missing rate 0.64%).</p> <p>Conclusions</p> <p>When collected as a long term clinical trial or biobank specimen for DNA, buffy coats can be stored for up to 9 years in a -80degC frozen state and still produce high yields of DNA suitable for GWA analysis and other genetic testing.</p> <p>Trial Registration</p> <p>The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial is registered with ClinicalTrials.gov, number <a href="http://www.clinicaltrials.gov/ct2/show/NCT00000620">NCT00000620</a>.</p