The feasibility of population screening for paroxysmal atrial fibrillation using hand-held electrocardiogram devices

Aims: There are few data on the feasibility of population screening for paroxysmal atrial fibrillation (AF) using hand-held electrocardiogram (ECG) devices outside a specialist setting or in people over the age of 75. We investigated the feasibility of screening when conducted without face-to-face contact (‘remote’) or via in-person appointments in primary care and explored impact of age on screening outcomes. Methods and results: People aged ≥65 years from 13 general practices in England participated in screening during 2019–20. This involved attending a practice nurse appointment (10 practices) or receiving an ECG device by post (three practices). Participants were asked to use a hand-held ECG for 1–4 weeks. Screening outcomes included uptake, quality of ECGs, AF detection rates, and uptake of anticoagulation if AF was detected. Screening was carried out by 2141 (87.5%) of people invited to practice nurse-led screening and by 288 (90.0%) invited to remote screening. At least 56 interpretable ECGs were provided by 98.0% of participants who participated for 3 weeks, with no significant differences by setting or age, except people aged 85 or over (91.1%). Overall, 2.6% (64/2429) screened participants had AF, with detection rising with age (9.2% in people aged 85 or over). A total of 53/64 (82.8%) people with AF commenced anticoagulation. Uptake of anticoagulation did not vary by age. Conclusion: Population screening for paroxysmal AF is feasible in general practice and without face-to-face contact for all ages over 64 years, including people aged 85 and over

Genetic engineering of human ES and iPS cells using TALE nucleases

Targeted genetic engineering of human pluripotent cells is a prerequisite for exploiting their full potential. Such genetic manipulations can be achieved using site-specific nucleases. Here we engineered transcription activator–like effector nucleases (TALENs) for five distinct genomic loci. At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location. Our data suggest that TALENs employing the specific architectures described here mediate site-specific genome modification in human pluripotent cells with similar efficiency and precision as do zinc-finger nucleases (ZFNs).National Institutes of Health (U.S.) (Grant R37-CA084198)National Institutes of Health (U.S.) (Grant RO1-CA087869)National Institutes of Health (U.S.) (Grant RO1-HD045022)Howard Hughes Medical Institut

Shading Beats Binocular Disparity in Depth from Luminance Gradients: Evidence against a Maximum Likelihood Principle for Cue Combination

Perceived depth is conveyed by multiple cues, including binocular disparity and luminance shading. Depth perception from luminance shading information depends on the perceptual assumption for the incident light, which has been shown to default to a diffuse illumination assumption. We focus on the case of sinusoidally corrugated surfaces to ask how shading and disparity cues combine defined by the joint luminance gradients and intrinsic disparity modulation that would occur in viewing the physical corrugation of a uniform surface under diffuse illumination. Such surfaces were simulated with a sinusoidal luminance modulation (0.26 or 1.8 cy/deg, contrast 20%-80%) modulated either in-phase or in opposite phase with a sinusoidal disparity of the same corrugation frequency, with disparity amplitudes ranging from 0’-20’. The observers’ task was to adjust the binocular disparity of a comparison random-dot stereogram surface to match the perceived depth of the joint luminance/disparitymodulated corrugation target. Regardless of target spatial frequency, the perceived target depth increased with the luminance contrast and depended on luminance phase but was largely unaffected by the luminance disparity modulation. These results validate the idea that human observers can use the diffuse illumination assumption to perceive depth from luminance gradients alone without making an assumption of light direction. For depth judgments with combined cues, the observers gave much greater weighting to the luminance shading than to the disparity modulation of the targets. The results were not well-fit by a Bayesian cue-combination model weighted in proportion to the variance of the measurements for each cue in isolation. Instead, they suggest that the visual system uses disjunctive mechanisms to process these two types of information rather than combining them according to their likelihood ratios

現地観測に基づく河川流の乱流特性に関する研究

博士（工学）神戸大

Opportunities and challenges of a novel cardiac output response to stress (CORS) test to enhance diagnosis of heart failure in primary care: qualitative study.

OBJECTIVE: To explore the role of the novel cardiac output response to stress (CORS), test in the current diagnostic pathway for heart failure and the opportunities and challenges to potential implementation in primary care. DESIGN: Qualitative study using semistructured in-depth interviews which were audio recorded and transcribed verbatim. Data from the interviews were analysed thematically using an inductive approach. SETTING: Newcastle upon Tyne, UK. PARTICIPANTS: Fourteen healthcare professionals (six males, eight females) from primary (general practitioners (GPs), nurses, healthcare assistant, practice managers) and secondary care (consultant cardiologists). RESULTS: Four themes relating to opportunities and challenges surrounding the implementation of the new diagnostic technology were identified. These reflected that the adoption of CORS test would be an advantage to primary care but the test had barriers to implementation which include: establishment of clinical utility, suitability for immobile patients and cost implication to GP practices. CONCLUSION: The development of a simple non-invasive clinical test to accelerate the diagnosis of heart failure in primary care maybe helpful to reduce unnecessary referrals to secondary care. The CORS test has the potential to serve this purpose; however, factors such as cost effectiveness, diagnostic accuracy and seamless implementation in primary care have to be fully explored.This study was funded by the UK Medical Research Council Confidence in Concept Scheme grant to DGJ (grant no. BH161161). SC and NO are supported by the European Horizon 2020 research and innovation programme under grant agreement no 777204. SG is supported by the NIHR MEDTEch In Vitro Diagnostics. DGJ is supported by the UK Research Councils’ Newcastle Centre for Ageing and Vitality (grant no. L016354)

Comparison of airway measurements during influenza-induced tachypnea in infant and adult cotton rats

<p>Abstract</p> <p>Background</p> <p>Increased respiratory rate (tachypnea) is frequently observed as a clinical sign of influenza pneumonia in pediatric patients admitted to the hospital. We previously demonstrated that influenza infection of adult cotton rats (<it>Sigmodon hispidus</it>) also results in tachypnea and wanted to establish whether this clinical sign was observed in infected infant cotton rats. We hypothesized that age-dependent differences in lung mechanics result in differences in ventilatory characteristics following influenza infection.</p> <p>Methods</p> <p>Lung tidal volume, dynamic elastance, resistance, and pleural pressure were measured in a resistance and compliance system on mechanically-ventilated anesthestized young (14–28 day old) and adult (6–12 week old) cotton rats. Animals at the same age were infected with influenza virus, and breathing rates and other respiratory measurements were recorded using a whole body flow plethysmograph.</p> <p>Results</p> <p>Adult cotton rats had significantly greater tidal volume (TV), and lower resistance and elastance than young animals. To evaluate the impact of this increased lung capacity and stiffening on respiratory disease, young and adult animals were infected intra-nasally with influenza A/Wuhan/359/95. Both age groups had increased respiratory rate and enhanced pause (<it>Penh</it>) during infection, suggesting lower airway obstruction. However, in spite of significant tachypnea, the infant (unlike the adult) cotton rats maintained the same tidal volume, resulting in an increased minute volume. In addition, the parameters that contribute to <it>Penh </it>were different: while relaxation time between breaths and time of expiration was decreased in both age groups, a disproportionate increase in peak inspiratory and expiratory flow contributed to the increase in <it>Penh </it>in infant animals.</p> <p>Conclusion</p> <p>While respiratory rate is increased in both adult and infant influenza-infected cotton rats, the volume of air exchanged per minute (minute volume) is increased in the infant animals only. This is likely to be a consequence of greater lung elastance in the very young animals. This model replicates many respiratory features of humans and consequently may be a useful tool to investigate new strategies to treat respiratory disease in influenza-infected infants.</p

X-Ray Spectroscopy of Stars

(abridged) Non-degenerate stars of essentially all spectral classes are soft X-ray sources. Low-mass stars on the cooler part of the main sequence and their pre-main sequence predecessors define the dominant stellar population in the galaxy by number. Their X-ray spectra are reminiscent, in the broadest sense, of X-ray spectra from the solar corona. X-ray emission from cool stars is indeed ascribed to magnetically trapped hot gas analogous to the solar coronal plasma. Coronal structure, its thermal stratification and geometric extent can be interpreted based on various spectral diagnostics. New features have been identified in pre-main sequence stars; some of these may be related to accretion shocks on the stellar surface, fluorescence on circumstellar disks due to X-ray irradiation, or shock heating in stellar outflows. Massive, hot stars clearly dominate the interaction with the galactic interstellar medium: they are the main sources of ionizing radiation, mechanical energy and chemical enrichment in galaxies. High-energy emission permits to probe some of the most important processes at work in these stars, and put constraints on their most peculiar feature: the stellar wind. Here, we review recent advances in our understanding of cool and hot stars through the study of X-ray spectra, in particular high-resolution spectra now available from XMM-Newton and Chandra. We address issues related to coronal structure, flares, the composition of coronal plasma, X-ray production in accretion streams and outflows, X-rays from single OB-type stars, massive binaries, magnetic hot objects and evolved WR stars.Comment: accepted for Astron. Astrophys. Rev., 98 journal pages, 30 figures (partly multiple); some corrections made after proof stag

Attenuation of Zinc Finger Nuclease Toxicity by Small-Molecule Regulation of Protein Levels

Zinc finger nucleases (ZFNs) have been used successfully to create genome-specific double-strand breaks and thereby stimulate gene targeting by several thousand fold. ZFNs are chimeric proteins composed of a specific DNA-binding domain linked to a non-specific DNA-cleavage domain. By changing key residues in the recognition helix of the specific DNA-binding domain, one can alter the ZFN binding specificity and thereby change the sequence to which a ZFN pair is being targeted. For these and other reasons, ZFNs are being pursued as reagents for genome modification, including use in gene therapy. In order for ZFNs to reach their full potential, it is important to attenuate the cytotoxic effects currently associated with many ZFNs. Here, we evaluate two potential strategies for reducing toxicity by regulating protein levels. Both strategies involve creating ZFNs with shortened half-lives and then regulating protein level with small molecules. First, we destabilize ZFNs by linking a ubiquitin moiety to the N-terminus and regulate ZFN levels using a proteasome inhibitor. Second, we destabilize ZFNs by linking a modified destabilizing FKBP12 domain to the N-terminus and regulate ZFN levels by using a small molecule that blocks the destabilization effect of the N-terminal domain. We show that by regulating protein levels, we can maintain high rates of ZFN-mediated gene targeting while reducing ZFN toxicity

Sequencing, de novo annotation and analysis of the first Anguilla anguilla transcriptome: EeelBase opens new perspectives for the study of the critically endangered european eel

Background: Once highly abundant, the European eel (Anguilla anguilla L.; Anguillidae; Teleostei) is considered to be critically endangered and on the verge of extinction, as the stock has declined by 90-99% since the 1980s. Yet, the species is poorly characterized at molecular level with little sequence information available in public databases.\ud \ud Results: The first European eel transcriptome was obtained by 454 FLX Titanium sequencing of a normalized cDNA library, produced from a pool of 18 glass eels (juveniles) from the French Atlantic coast and two sites in the Mediterranean coast. Over 310,000 reads were assembled in a total of 19,631 transcribed contigs, with an average length of 531 nucleotides. Overall 36% of the contigs were annotated to known protein/nucleotide sequences and 35 putative miRNA identified.\ud \ud Conclusions: This study represents the first transcriptome analysis for a critically endangered species. EeelBase, a dedicated database of annotated transcriptome sequences of the European eel is freely available at http://compgen.bio.unipd.it/eeelbase. Considering the multiple factors potentially involved in the decline of the European eel, including anthropogenic factors such as pollution and human-introduced diseases, our results will provide a rich source of data to discover and identify new genes, characterize gene expression, as well as for identification of genetic markers scattered across the genome to be used in various applications

Methicillin-Resistant Staphylococcus aureus (MRSA) Strain ST398 Is Present in Midwestern U.S. Swine and Swine Workers

BACKGROUND: Recent research has demonstrated that many swine and swine farmers in the Netherlands and Canada are colonized with MRSA. However, no studies to date have investigated carriage of MRSA among swine and swine farmers in the United States (U.S.). METHODS: We sampled the nares of 299 swine and 20 workers from two different production systems in Iowa and Illinois, comprising approximately 87,000 live animals. MRSA isolates were typed by pulsed field gel electrophoresis (PFGE) using SmaI and EagI restriction enzymes, and by multi locus sequence typing (MLST). PCR was used to determine SCCmec type and presence of the pvl gene. RESULTS: In this pilot study, overall MRSA prevalence in swine was 49% (147/299) and 45% (9/20) in workers. The prevalence of MRSA carriage among production system A's swine varied by age, ranging from 36% (11/30) in adult swine to 100% (60/60) of animals aged 9 and 12 weeks. The prevalence among production system A's workers was 64% (9/14). MRSA was not isolated from production system B's swine or workers. Isolates examined were not typeable by PFGE when SmaI was used, but digestion with EagI revealed that the isolates were clonal and were not related to common human types in Iowa (USA100, USA300, and USA400). MLST documented that the isolates were ST398. CONCLUSIONS: These results show that colonization of swine by MRSA was very common on one swine production system in the midwestern U.S., suggesting that agricultural animals could become an important reservoir for this bacterium. MRSA strain ST398 was the only strain documented on this farm. Further studies are examining carriage rates on additional farms