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Barriers to rapid return of sequencing results can affect the utility of sequence data for infection prevention and control decisions.To undertake a mixed-methods analysis to identify challenges that sites faced in achieving a rapid turnaround time (TAT) in the COVID-19 Genomics UK Hospital-Onset COVID-19 Infection (COG-UK HOCI) study.For the quantitative analysis, timepoints relating to different stages of the sequencing process were extracted from both the COG-UK HOCI study dataset and surveys of study sites. Qualitative data relating to the barriers and facilitators to achieving rapid TATs were included from thematic analysis.The overall TAT, from sample collection to receipt of sequence report by infection control teams, varied between sites (median 5.1 days, range 3.0-29.0 days). Most variation was seen between reporting of a positive COVID-19 polymerase chain reaction (PCR) result to sequence report generation (median 4.0 days, range 2.3-27.0 days). On deeper analysis, most of this variability was accounted for by differences in the delay between the COVID-19 PCR result and arrival of the sample at the sequencing laboratory (median 20.8 h, range 16.0-88.7 h). Qualitative analyses suggest that closer proximity of sequencing laboratories to diagnostic laboratories, increased staff flexibility and regular transport times facilitated a shorter TAT.Integration of pathogen sequencing into diagnostic laboratories may help to improve sequencing TAT to allow sequence data to be of tangible value to infection control practice. Adding a quality control step upstream to increase capacity further down the workflow may also optimize TAT if lower quality samples are removed at an earlier stage.

A neuroimaging-based biomarker termed the brain age is thought to reflect variability in the brain's ageing process and predict longevity. Using Insight 46, a unique narrow-age birth cohort, we aimed to examine potential drivers and correlates of brain age.Participants, born in a single week in 1946 in mainland Britain, have had 24 prospective waves of data collection to date, including MRI and amyloid PET imaging at approximately 70 years old. Using MRI data from a previously defined selection of this cohort, we derived brain-predicted age from an established machine-learning model (trained on 2001 healthy adults aged 18-90 years); subtracting this from chronological age (at time of assessment) gave the brain-predicted age difference (brain-PAD). We tested associations with data from early life, midlife, and late life, as well as rates of MRI-derived brain atrophy.Between May 28, 2015, and Jan 10, 2018, 502 individuals were assessed as part of Insight 46. We included 456 participants (225 female), with a mean chronological age of 70·7 years (SD 0·7; range 69·2 to 71·9). The mean brain-predicted age was 67·9 years (8·2, 46·3 to 94·3). Female sex was associated with a 5·4-year (95% CI 4·1 to 6·8) younger brain-PAD than male sex. An increase in brain-PAD was associated with increased cardiovascular risk at age 36 years (β=2·3 [95% CI 1·5 to 3·0]) and 69 years (β=2·6 [1·9 to 3·3]); increased cerebrovascular disease burden (1·9 [1·3 to 2·6]); lower cognitive performance (-1·3 [-2·4 to -0·2]); and increased serum neurofilament light concentration (1·2 [0·6 to 1·9]). Higher brain-PAD was associated with future hippocampal atrophy over the subsequent 2 years (0·003 mL/year [0·000 to 0·006] per 5-year increment in brain-PAD). Early-life factors did not relate to brain-PAD. Combining 12 metrics in a hierarchical partitioning model explained 33% of the variance in brain-PAD.Brain-PAD was associated with cardiovascular risk, and imaging and biochemical markers of neurodegeneration. These findings support brain-PAD as an integrative summary metric of brain health, reflecting multiple contributions to pathological brain ageing, and which might have prognostic utility.Alzheimer's Research UK, Medical Research Council Dementia Platforms UK, Selfridges Group Foundation, Wolfson Foundation, Wellcome Trust, Brain Research UK, Alzheimer's Association.

Functional tricuspid regurgitation (TR) is a common pathophysiologic condition in adults with ostium secundum atrial septal defect (ASD). The aim of this study was to evaluate long-term outcomes following transcatheter ASD closure, which have not been well studied among patients with significant TR.We reviewed consecutive adult patients who underwent transcatheter ASD closure at Toronto General Hospital, Ontario, Canada, from 1998 to 2016. We linked our hospital registry with Ontario population-based health administrative databases to collect longitudinal data on inpatient and outpatient health care utilisation and vital status.In this cohort study of 949 patients, 199 (22%) had moderate to severe TR before transcatheter ASD closure. A significant proportion of patients (61%) showed improvement in TR severity to at least mild TR after ASD intervention. At a median follow-up of 10.9 years, patients with baseline mild or no TR, compared with those with greater than moderate TR, had significantly lower rates of all-cause mortality (6.8 vs 22.5 per 1000 person-years [PY]; P0.001), composite hospitalisation for atrial fibrillation (AF) or heart failure (HF) (22.3 vs 49.1 per 1000 PY; P0.001), and new onset of AF (10.4 vs 20.2 per 1000 PY; P = 0.002) and HF (5.0 vs 9.2 per 1000 PY; P = 0.039). Preprocedural TR was independently associated with higher all-cause mortality (adjusted hazard ratio 1.69, 95% confidence interval 1.08-2.62).TR severity was independently associated with a higher risk of mortality and morbidity. Further investigation of earlier device closure or concomitant tricuspid valve intervention may be of interest.

Alcoholic hepatitis (AH) is a severe condition with poor short-term prognosis. Specific treatment with corticosteroids slightly improves short-term survival but is associated with infection and is not used in many centers. A reliable method to identify patients who will recover spontaneously will minimise the numbers of patients who experience side effects of available treatments.We analysed the trajectory of serum bilirubin concentration over the course of hospital admissions in patients with AH to predict spontaneous survival and the need for treatment.data from 426 patients were analysed. Based on bilirubin trajectory, patients were categorized into three groups: 'fast fallers' (bilirubin0.8 x admission value at day 7), 'static' (bilirubin of0.9 -1.2 x admission value) and 'rapid risers' (bilirubin of ≥1.2 x admission bilirubin). Fast fallers had significantly better 90-day survival compared to other groups (log rank p.001), and showed no benefit of corticosteroid therapy (OR for survival at 28 days of treatment, 0.94, 95% CI 0.06 - 8.41). These findings remained even amongst patients with severe disease based on initial DF, GAHS or MELD scores.We present an intuitive method of classifying patients with AH based on the trajectory of bilirubin over the first week of admission. It is complimentary to existing scores that identify candidates for corticosteroid treatment or assess response to treatment. This method identifies a group of patients with AH who recover spontaneously and can avoid corticosteroid therapy.

This study aimed to compare the efficacy and safety of ablation with high and low power settings using either a flexible tip or straight SF tip irrigated catheter in the left ventricle (LV) using a peripheral microemboli monitoring system.The microemboli risk of flexible and straight SF tip irrigated catheters in creating ablative lesions in the LV at variable power settings has not been adequately assessed.Six pigs underwent catheter ablation in the LV using a flexible tip or straight SF tip catheter with 2 energy settings (30 or 50 W, 30 seconds, irrigation saline 17 mL/min).A total of 79 radiofrequency (RF) applications were assessed. High power settings via a flexible tip formed a significantly higher arterial microbubble volume in the extracorporeal circulation (P = 0.005). Notably, RF applications with a steam pop induced an exponential increase of microbubble volume with both catheters. A higher power setting induced a significantly higher number of microembolic signals on carotid artery Doppler ultrasound with a flexible tip irrigated catheter (P 0.001). Similarly, the straight SF tip irrigated catheter tended to increase the number of microembolic signals with 50 W (P = 0.091).RF ablation at high power settings in the LV carries a risk of microembolic events compared with lower power settings. When high power settings are used for creating ablative lesions for deep intramural foci in the LV, the risk of microembolic events induced by RF ablation should be carefully monitored.

Achievement emotions are important educational constructs. They predict outcomes such as students’ achievement, persistence, and drop-out intentions. Thus, it is crucial to examine the factors that determine these emotions. In this study, we focus specifically on the positive emotion of enjoyment as past research has largely focused on negative emotions such as test anxiety. We explore two potential predictors of enjoyment: individual-student achievement and class-average achievement. Past research has shown student achievement to be a positive predictor of enjoyment, with preliminary evidence suggesting class-average achievement to be a negative predictor of enjoyment (Happy-Fish-Little-Pond Effect; HFLPE). However, research has largely been restricted to single-country or single-domain examinations with samples of secondary school students, limiting the generalizability of findings. To bridge this gap, we utilize combined data from the Progress in International Reading Literacy Study (PIRLS) and the Trends in International Mathematics and Science Study (TIMSS) 2011. This sample consisted of 180,084 4th-grade students from 37 countries, with all students responding to items in the math, science, and reading domains. Through multilevel modeling, we demonstrate that the effect of student achievement on enjoyment is positive in all three domains, while the effect of class achievement is negative—confirming the HFLPE. We also demonstrate the relative universality of these results across the 37 countries; while there was variation in the size of the effects, results were largely consistent in direction. Our findings add to the literature on achievement emotions by highlighting two important predictors of enjoyment that operate across domains and cross-nationally.

Irrigated needle catheter ablation is efficacious for creation of transmural lesions in the left ventricle (LV). However, interdependence of needle orientation and myocardial fiber orientation and the resulting influence on lesion creation remain unclear.The purpose of this study was to investigate the impact of myocardial fiber orientation on reproducibility and controllability of lesion creation in LV myocardium using a heated saline-enhanced radiofrequency (SERF) needle-tip catheter system.Eleven dogs underwent catheter ablation using this novel catheter. Ablative lesions were created using different power and ablation times (15-50 W; application 25-120 seconds; 60°C irrigation saline at 10 mL/min). Hearts were explanted, and lesions were evaluated using 3-T cardiac magnetic resonance (CMR), gross pathologic, and histologic investigations.Forty-three of 57 lesions (75.4%) were transmural, and lesion depth reached approximately 90% of LV wall thickness. Lesion volume in both gross pathology and ex vivo CMR showed a positive linear correlation with power × radiofrequency (RF) time index (r = 0.637, P.001; and r = 0.786, P.001, respectively). Maximum width (circumferential direction of LV) and maximum length (long-axis direction) of all lesions were distributed in the middle layer of LV where myocardium runs circumferentially. Paired-sample t-test showed maximum lesion width was significantly greater than maximum lesion length by both CMR and gross pathologic evaluation (26.1 ± 9.6 mm vs 17.2 ± 6.7 mm, P.001; and 22.5 ± 7.7 mm vs 18.6 ± 5.9 mm, P.001, respectively).This catheter showed feasibility in creating transmural LV lesions. Power × RF time index was strongly correlated with lesion volume and predicted lesion size. More importantly, SERF lesions extended along the myocardial fiber orientation.

Clinical practice guidelines (CPGs) have been associated with improved patient outcomes. We aimed to evaluate institutional CPG adherence and hypothesized that adherence would be associated with fewer complications in pediatric appendicitis.A retrospective review was conducted of pediatric (18 y) appendicitis patients who underwent appendectomy (6/1/2017-5/30/2018). Patients were managed using an institutional pediatric appendicitis CPG. The primary outcome was CPG adherence, defined as receipt of preoperative antibiotics at diagnosis, surgical prophylaxis before incision, and, in perforated/gangrenous appendicitis, continued postoperative antibiotics, and prescription for discharge antibiotics. Univariate and multivariate analyzes were performed.Among 399 patients, the baseline characteristics were similar between CPG-adherent and nonadherent patients. Overall CPG adherence was low at 55% (n = 221). Only 58% of patients received preoperative antibiotics per protocol (n = 233). Patients with simple appendicitis were more likely to proceed to surgery without receiving any preoperative antibiotics (35% vs. 21%, P = 0.004). Surgical prophylaxis compliance was high at 97% (n = 389). CPG violation was associated with reoperation (n = 5 versus 0, P = 0.02). After adjusting for age and admission white blood cell count, the association between CPG adherence and postoperative surgical site infection or intra-abdominal abscess remained nonsignificant (OR: 1.2, 95% CI: 0.5-2.5).Despite a long-standing pediatric appendicitis CPG, adherence with antibiotic components of the CPG was poor. CPG violation was significantly associated with reoperation, but was not associated with other postoperative complications. Regular audits of CPG adherence are necessary to ascertain reasons for noncompliance and identify ways to improve adherence.

Based on limited evidence, the American Pediatric Surgical Association recommends 5-7 d of postoperative antibiotics in perforated appendicitis for preventing intra-abdominal abscess (IAA). In 2015, our institutional clinical practice guideline was modified to standardize prescription for 7 additional days of oral antibiotics after discharge. We hypothesized that prescribing oral antibiotics after discharge would be associated with fewer complications in perforated appendicitis.A retrospective cohort study was conducted of pediatric (younger than 18 y) patients who underwent laparoscopic appendectomy for perforated appendicitis (August 1, 2012-April 30, 2019). Patients diagnosed with IAA before discharge or with a postoperative length of stay ≥8 d were excluded. Patient outcomes were compared prestandardization and poststandardization of discharge antibiotics.Of 617 patients, 212 (34.5%) were admitted prestandardization and 404 (65.5%) poststandardization. Overall, 409 patients (66.3%) received discharge antibiotics. The median total postoperative antibiotic duration was 4 d (interquartile range, 3-5) prestandardization versus 11 d (interquartile range, 10-12) poststandardization (P 0.001). Prestandardization patients had a higher rate of IAA (8.9% versus 4.5%, P = 0.03) and were readmitted more frequently (13.1% versus 6.4%, P = 0.005). On adjusted analysis, admission poststandardization was associated with reduced odds of IAA (odds ratio, 0.51; 95% confidence interval, 0.25-1.06), but the relationship was imprecise. Admission poststandardization was significantly associated with reduced adjusted odds of readmission (odds ratio, 0.46; 95% confidence interval, 0.25-0.85).Prescription for seven additional days of oral antibiotics after discharge was associated with reduced odds of readmission in pediatric perforated appendicitis. This population may benefit from a longer postoperative antibiotic course than currently recommended.

Background The cryoballoon (CB) catheter is an established tool for pulmonary vein isolation (PVI), but its use is limited for that purpose. Objective The purpose of this study was to investigate the biophysical properties of a newly developed linear cryoablation catheter for creation of linear ablation lesions in an in vivo model. Methods Twenty-nine dogs (14 acutely ablated, 15 chronically followed) underwent cryoablation using the linear cryoablation catheter. Regions of interest included the cavotricuspid isthmus (CTI), mitral isthmus (MI), left atrial (LA) roof, and LA posterior wall in an acute study. Cryoablations for CTI and MI were performed in 14 atrial fibrillation animals after PVI and followed over 1 month in the chronic study. Tissue temperature during cryoablation was monitored using implanted thermocouples in the regions of interest. Gross and microscopic pathologic characteristics of the lesions were assessed. Results In acute animals, lesion length (transmurality) was CTI 34 ± 4 mm (89% ± 11%); MI 29 ± 4 mm (90% ± 13%); LA roof 19 ± 3 mm (90% ± 8%); and LA posterior wall 19 ± 2 mm (81% ± 13%), with 1 or 2 freezes. Chronic bidirectional block was achieved in 13 of 14 CTI (93%) and 10 of 14 MI (71%) ablations after 1-month follow-up and was consistent with lesion continuity and transmurality upon pathology. The lowest tissue temperature correlated well with the closest distance to the linear cryocatheter (r = 0.688; P Conclusion This linear cryocatheter created continuous and transmural linear lesions with “single-shot” cryoenergy application and has the potential for clinical use in the setting of various arrhythmias.

Background The relative influences of baseline risk factors for pediatric nonaccidental burns have not been well described. We evaluated baseline characteristics of pediatric nonaccidental burn patients and their primary caretakers. Methods A single-center retrospective cohort study was conducted of pediatric (age, Highlights • Non-Hispanic black children had higher rates of Child Protective Services referral. • Non-Hispanic black children had higher rates of nonaccidental burn diagnosis. • Caretaker history with Child Protective Services correlated with nonaccidental burns. • Patient non-Hispanic black race/ethnicity was associated with nonaccidental burn.

Poorly controlled type 2 diabetes mellitus is associated with the development of cardiovascular and renal complications, resulting in significant morbidity and mortality. Intensive glycemic control has been a major focus for clinical trials and novel drug development. However, narrow treatment strategies developed strictly for glycemic control did not confer a large risk reduction in cardiovascular events. There were also only modest effects in reducing the progression of diabetic kidney disease. Recent cardiovascular safety trials and the dedicated renal protection trial CREDENCE (Canagliflozin on Renal and Cardiovascular Outcomes in Participants with Diabetic Nephropathy) have shown that the sodium-glucose cotransporter-2 (SGLT2) inhibitors, a newer generation of antihyperglycemic agents, improve both cardiovascular and renal outcomes when added to guideline-recommended treatment. This review examines the current evidence on the mechanism underlying the cardiorenal effects of SGLT2 inhibitors and summarizes clinical trial evidence and safety data related to the use of SGLT2 inhibitors for cardiovascular and renal protection.

Background Noninvasive cardiac ablation of ventricular tachycardia (VT) using radiotherapy has recently gained interest among electrophysiologists. The effects of left ventricular (LV) ablative radiation treatment on global LV function and volumes are unknown. Objective The purpose of this study was to investigate the effects of noninvasive ablation on LV function over time. Methods Twenty domestic swine underwent proton beam treatment of LV sites in a dose-finding design and were followed for up to 40 weeks by cardiac magnetic resonance imaging at 4-week intervals. Doses investigated were either 40 Gy at 1 site (n = 8) or 30 Gy at 2 sites (n = 4) in the low-dose group and 40 Gy at 3 sites (n = 8) in the high-dose group. Results LV mean dose (13.2 ± 1.8 Gy vs 4.6 ± 1.8 Gy) and the volume receiving at least 20 Gy (V20Gy) (24.7% ± 4.8% vs 6.4% ± 3.0%) differed significantly between groups. Dose-dependent effects on left ventricular ejection fraction (LVEF) and LV end-diastolic volume became manifest about 3 months after treatment. LVEF decline was correlated to mean dose (correlation coefficient ρ = –0.69; P = .008) and V20Gy (ρ = –0.66; P = .01), as was LV dilation (ρ = 0.72; P = .005; and ρ = 0.75, P = .003 respectively). Conclusion Possible adverse effects on LV function, seen about 3 months after treatment, are dose dependent. Therefore, precise target definition and focused energy delivery are paramount in catheter-free ablation.

Allosteric integrase inhibitors (ALLINIs) of HIV-1 may hold promise as a novel mechanism for HIV therapeutics and cure. Scaffold modifications to the 4-(4,4-dimethylpiperidinyl) 2,6-dimethylpyridinyl class of ALLINIs provided a series of potent compounds with differentiated 5/6 fused ring systems. Notably, inhibitors containing the 1,2,4-triazolopyridine and imidazopyridine core exhibited single digit nM antiviral potency and low to moderate clearance after intravenous (IV) dosing in rat pharmacokinetic (PK) studies. The 1,2,4-triazolopyridines showed a higher oral exposure when compared to the imidazopyridines. Further modifications to the C5 substituent of the 1,2,4-triazolopyridines resulted in a new lead compound, which had improved rat IV/PO PK compared to the former lead compound GSK3739936, while maintaining antiviral potency. Structure-activity relationships (SAR) and rat pharmacokinetic profiles of this series are discussed.

This article focuses on the resiliency of refugee families and the various ways that pediatric practitioners can use and strengthen those resiliencies in the course of pediatric health care delivery. It reviews common stressors experienced by refugees, information about the concept of resilience, aspects of culturally responsive health care, and clinical recommendations. In addition, 3 cases are presented that highlight both resiliencies of refugee families and successful interventions by pediatric health care providers within the pediatric refugee clinic at the Children's Hospital of Philadelphia.

Elevations in brain interleukin-1 beta (IL-1β) during chronic stress exposure have been implicated in behavioral and cognitive impairments associated with depression and anxiety. Two critical regulators of brain IL-1β production during times of stress are glucocorticoids and catecholamines. These hormones work in opposition to one another to inhibit (via glucocorticoid receptors) or stimulate (via beta-adrenergic receptors: β-AR) IL-1 β production. While chronic stress often heightens both corticosterone and catecholamine levels, it remains unknown as to how chronic stress may affect the “yin-yang” balance between adrenergic stimulation and glucocorticoid suppression of brain IL-1β. To investigate this further, male and female rats underwent 4 days of stress exposure or served as non-stressed controls. On day 5, animals were administered propranolol (β-AR antagonist), metyrapone (a glucocorticoid synthesis inhibitor), vehicle, or both drugs and brain IL-1β mRNA was measured by rtPCR in limbic brain areas. In males, administration of propranolol had no effect on IL-1β expression in non-stressed controls but significantly reduced IL-1β in the hippocampus and amygdala of chronically stressed animals. In females, propranolol significantly reduced IL-1β in the amygdala and hypothalamus of both control and stressed rats. In male rats, metyrapone treatment significantly increased IL-1β mRNA regardless of stress treatment in all brain areas, while in female rats metyrapone only increased IL-1β in the hypothalamus. Interestingly, propranolol treatment blocked the metyrapone-induced increase in brain IL-1β indicating the increase in brain IL-1β following metyrapone treatment was due to increase β-AR activation. Additional studies revealed that metyrapone significantly increases norepinephrine turnover in the hypothalamus and medial prefrontal cortex in male rats and that microglia appear to be the cell type contributing to the production of IL-1β. Overall, data reveal that stress exposure in male rats affects the regulation of brain IL-1β by the norepinephrine-β-AR pathway, while stress had no effect in the regulation of brain IL-1β in female rats.

Purpose/Objective(s) To determine the facilitators, barriers, and decision making needs of caregivers of patients receiving palliative intent radiation therapy Materials/Methods Systematic review of articles utilizing PRISMA guidelines was performed. Inclusion criteria included studies published from 2007 to 2018 focusing on caregivers of patients receiving palliative intent radiation therapy (PRT) for advanced cancers. Pediatric and non-English articles were excluded. Rayyan QCRI was utilized to screen abstracts, and Covidence organized the review of full text articles by 2 reviewers. Results Of 6079 articles identified, 36 were selected for full text review, and 6 met inclusion. Limited literature was found. Caregivers experience anxiety, fatigue, and hopelessness. Caregivers need more information and their emotions impact both the receipt of radiation therapy and satisfaction with services. Conclusion While limited, literature focusing on caregivers of patients undergoing palliative intent radiation therapy consistently find unmet caregiver education and emotional distress which impact patient receipt of and satisfaction with PRT services. More research is needed to better understand needs of caregivers of patients with advanced cancers undergoing PRT.

The office has become a large scale organisational phenomenon accommodating large numbers of organisational employees most often housed in open plan and Activity Based Working settings that arguably resemble the new factory. This study examines contemporary Big 4 accounting firm office design innovations and their representation with a view to eliciting their claimed rationales, reflections of historical office design and management thinking, and apparent strategic agendas with respect to office efficiency, client relations and cost control involved in their offering of professional services. In doing so, it also explores the implications that public practice firms' office design may have for auditor independence and audit quality. Informed by Goffman's theories of impression management, the study employs historical and website analysis, finding a predominant firm focus on office efficiency and client relations with an undercurrent of cost reduction and revenue enhancement aspirations. While represented as innovative current office design and work pattern developments, public practice accounting firm office innovations and intentions are found to significantly reflect historical office design and management thinking, with dramaturgical circumspection of floor designs and props oriented towards creating front stage performances predesigned for clients' impression management. Where backstage redesign and frame breaking does not produce desired employee performance changes, some signs of retreating to more traditional floor redesign and territorial marker usage are evident. The study also signals the potential for innovative accounting firm office designs to carry some significant impacts upon audit independence and audit quality.

Neutron resonance absorption imaging, being used to visualize a spatial distribution of elements and/or temperature within a sample, is one of the important applications of an intense short-pulse neutron source. Two-dimensional time-analyzer neutron detectors are indispensable to perform neutron energy dependent imaging by means of the time-of-flight technique. Some state-of-the-art time-analyzer neutron detectors have been developed for thermal or cold neutrons. However the detection efficiencies of such neutron detectors are not sufficient for neutron resonance absorption imaging which utilizes neutrons in the energy region from eV to keV. The 2012 model lithium-6 time-analyzer neutron detector (LiTA12) system, based on a lithium glass scintillator and multi-anode photomultiplier tube, has the highest neutron efficiency among the detectors for pulsed neutron imaging together with the flexibility to tune the efficiency by changing the thickness of the lithium glass. The authors estimated performances of the detector at resonance neutron energies finding that 0.7 mm width line pairs made by 3 μm thick gold could be resolved at 4.9 eV and the maximum count rate of 8 Mcps was achieved at 1 keV.

We are developing practical material observation methods using neutron imaging at J-PARC Materials and Life Science Experimental Facility (MLF). Neutron Bragg-edge transmission (BET) imaging, one of the energy-resolved neutron imaging methods, makes it possible to quantitatively visualize the two-dimensional distribution of physical properties within a sample. Here, we report two application examples. First, feasibility of measuring the temperature distribution of a copper rod through the thermal expansion of the lattice constant using BET spectral analysis was studied. Second, visualization of the texture variation and the strain distribution of a bent steel plate through the 2D-BET imaging method were performed. The obtained results for both experiments were compared with those obtained by the neutron diffraction (ND) method.

We have studied the effect of beam collimation on the quality of images obtained with Talbot-Lau interferometry at the RADEN beam line in the J-PARC Materials and Life Science Experimental Facility. By using four typical beam collimations of RADEN, which were determined at a position relatively far from the interferometer, the blurring of images and the average intensity and visibility of interference patterns were observed. From these data, spatial resolutions and measurement precisions of images were experimentally evaluated. The obtained characteristics on each collimation condition are useful to design and optimize a new interferometer, and perform experiments at this beam line.

Background: Recently emerging SARS-CoV-2 variants have been associated with an increased rate of transmission within the community. Little is known about the impact their increased infectivity has on transmission within hospitals. Methods: We collected viral sequences and epidemiological data of patients with community and healthcare associated SARS-CoV-2 infections, sampled from 16th November 2020 to 10th January 2021, from nine hospitals participating in the COG-UK HOCI study. Outbreaks were identified using ward information, lineage and pairwise genetic differences between viral sequences. Findings: Mixed effects logistic regression analysis of 4184 sequences showed healthcare-acquired infections were no more likely to be identified as the Alpha variant than community acquired infections. Nosocomial outbreaks were investigated based on overlapping ward stay and SARS-CoV-2 genome sequence similarity. There was no significant difference in the number of patients involved in outbreaks caused by the Alpha variant compared to outbreaks caused by other lineages. Interpretation: Notwithstanding evidence from community studies that the Alpha variant is more transmissible, we find no evidence to support it causing more nosocomial transmission than previous lineages. This suggests that the stringent infection prevention measures already in place in UK hospitals contained the spread of the Alpha variant as effectively as other less transmissible lineages, providing reassurance of their efficacy against emerging variants of concern. Funding Information: COG-UK HOCI funded by COG-UK consortium. The COG-UK consortium is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute. Declaration of Interests: None to declare. Ethics Approval Statement: Ethical approval for the HOCI study was provided by REC 20/EE/0118.

We provide a rich multi-contrast microstructural MRI dataset acquired on an ultra-strong gradient 3T Connectom MRI scanner comprising 5 repeated sets of MRI microstructural contrasts in 6 healthy human participants. The availability of data sets that support comprehensive simultaneous assessment of test-retest reliability of multiple microstructural contrasts (i.e., those derived from advanced diffusion, multi-component relaxometry and quantitative magnetisation transfer MRI) in the same population is extremely limited. This unique dataset is offered to the imaging community as a test-bed resource for conducting specialised analyses that may assist and inform their current and future research. The Microstructural Image Compilation with Repeated Acquisitions (MICRA) dataset includes raw data and computed microstructure maps derived from multi-shell and multi-direction encoded diffusion, multi-component relaxometry and quantitative magnetisation transfer acquisition protocols. Our data demonstrate high reproducibility of several microstructural MRI measures across scan sessions as shown by intra-class correlation coefficients and coefficients of variation. To illustrate a potential use of the MICRA dataset, we computed sample sizes required to provide sufficient statistical power a priori across different white matter pathways and microstructure measures for different statistical comparisons. We also demonstrate whole brain white matter voxel-wise repeatability in several microstructural maps. The MICRA dataset will be of benefit to researchers wishing to conduct similar reliability tests, power estimations or to evaluate the robustness of their own analysis pipelines.

The immigrant paradox is the phenomenon where recent immigrants have better outcomes than individuals from native-born families. Although limited past research has shown the paradox to exist for math self-concept, neither its exact nature nor a theoretical explanation for its existence have been reported. Using Australian cohort data from the Programme for International Student Assessment (PISA) 2003 (N = 12,551) and 2012 (N = 14,481), we first establish that immigrant students have higher math self-concepts than native students, controlling for gender and absolute parental socioeconomic status (SES), and show that it is similar to—albeit weaker than—the expectation-achievement gap. We then provide an SES-of-origin-country hypothesis as a contextual explanation for this effect; we show that the immigrant paradox for both math self-concept and educational expectations substantially reduces when accounting for parents' SES relative to their country-of-origin. Our findings suggest that the paradox for math self-concept and educational expectations may partly result from immigrant parents’ socioeconomic advantage in their home countries.

We report four fatal cases of fulminant reversible cerebral vasoconstriction syndrome, all initially diagnosed as primary central nervous system vasculitis and treated with corticosteroids. Although reversible cerebral vasoconstriction syndrome is usually self-limiting without permanent neurologic deficits, rarely it can be fatal and worse outcomes have been associated with corticosteroid treatment.

Although women have made substantial progress in the uptake of undergraduate and graduate study in science, technology, engineering, and mathematics (STEM) fields, they remain under-represented overall. The gender gap in STEM enrolment is related to differences in attitudes toward science rather than differences in mathematical and scientific ability. We explored the factors influencing adolescent girls’ interest in science, with a focus on the interplay between cultural factors and parental occupation.

Background & Aims While abstinence-promoting behavioral and pharmacotherapies are part of the therapeutic foundation for alcohol use disorder (AUD) and alcohol-associated liver disease (ALD), these therapies, along with alcohol screening and education, are often underutilized. Our aim was to examine provider attitudes and practices for alcohol screening, treatment and education in patients with liver disease. Methods We conducted a survey of primarily (89%) hepatology and gastroenterology providers within (80%) and outside the United States (20%). Surveys were sent to 921 providers with 408 complete responses (44%), of whom 343 (80%) work in a tertiary liver transplant center. Results While alcohol screening rates in liver disease patients was nearly universal, less than half of providers reported practicing with integrated addiction providers, using alcohol biomarkers and screening tools. Safe alcohol use by liver disease patients was felt to exist by 40% of providers. While 60% of providers reported referring AUD patients for behavioral therapy, 71% never prescribed AUD pharmacotherapy due to low comfort (84%). Most providers (77%) reported low addiction education and 90% desired more during GI/hepatology fellowship training. Amongst prescribers, baclofen was preferred, but with gaps in pharmacotherapy knowledge. Overall, there was low adherence to the 2019 AASLD practice guidance for ALD, although higher in hepatologists and experienced providers. Conclusions While our survey of hepatology and gastroenterology providers demonstrated higher rates of alcohol screening and referrals for behavioral therapy, we found low rates of prescribing AUD pharmacotherapy due to knowledge gaps from insufficient education. Further studies are needed to assess interventions to improve provider alignment with best practices for treating patients with AUD and ALD.

Alcoholic liver disease (ALD) is a leading cause of chronic liver disease with a wide spectrum of manifestations including simple steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Liver injury in ALD is caused by chronic inflammation, which has been actively investigated as a therapeutic target for the treatment of ALD for over the last four decades. In this review, we summarize a wide variety of inflammatory mediators that have been shown to contribute to the pathogenesis of ALD, and discuss the therapeutic potential of these mediators for the treatment of ALD.

Non-invasive hemodynamic monitoring has the potential to be a valuable clinical tool for the screening and management of hypertensive disorders of pregnancy. The objective of this study was to validate the clinical utility of the non-invasive cardiac output monitoring (NICOM) system in pregnant women.Twenty healthy pregnant women with a singleton pregnancy at 22 to 26 weeks' gestation were enrolled in this study. Measures of heart rate, stroke volume, and cardiac output were obtained through NICOM and compared with Doppler echocardiography.NICOM significantly overestimated measures of both stroke volume and cardiac output compared with Doppler echocardiography (95 ± 4 vs. 73 ± 4 mL, P0.0001; and 7.4 ± 0.2 vs. 5.6 ± 0.2 L/min, P0.0001; respectively).There is no gold standard for the measurement of cardiac output in the setting of pregnancy. However, once normal values have been established, NICOM has the potential to be a useful clinical tool for monitoring maternal hemodynamics in pregnant women. Further investigation regarding the validity of NICOM is required in larger populations of healthy and hypertensive pregnant women to determine whether this device is appropriate for maternal hemodynamic assessment during pregnancy.

Since zwitterionic benzenesulfonamide Nav1.7 inhibitors suffer from poor membrane permeability, we sought to eliminate this characteristic by replacing the basic moiety with non-basic bicyclic acetals and monocyclic ethers. These efforts led to the discovery of the non-zwitterionic aryl sulfonamide 49 as a selective Nav1.7 inhibitor with improved membrane permeability. Despite its moderate cellular activity, 49 exhibited robust efficacy in mouse models of neuropathic and inflammatory pain and modulated translational electromyogram measures associated with activation of nociceptive neurons.