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Marine animal biomass is expected to decrease in the 21st century due to climate driven changes in ocean environmental conditions. Previous studies suggest that the magnitude of the decline in primary production on apex predators could be amplified through the trophodynamics of marine food webs, leading to larger decreases in the biomass of predators relative to the decrease in primary production, a mechanism called trophic amplification. We compared relative changes in producer and consumer biomass or production in the global ocean to assess the extent of trophic amplification. We used simulations from nine marine ecosystem models (MEMs) from the Fisheries and Marine Ecosystem Models Intercomparison Project forced by two Earth System Models under the high greenhouse gas emissions Shared Socioeconomic Pathways (SSP5-8.5) and a scenario of no fishing. Globally, total consumer biomass is projected to decrease by 16.7 ± 9.5% more than net primary production (NPP) by 2090-2099 relative to 1995-2014, with substantial variations among MEMs and regions. Total consumer biomass is projected to decrease almost everywhere in the ocean (80% of the worlds oceans) in the model ensemble. In 40% of the worlds oceans, consumer biomass was projected to decrease more than NPP. Additionally, in another 36% of the worlds oceans consumer biomass is expected to decrease even as projected NPP increases. By analysing the biomass response within food webs in available MEMs, we found that model parameters and structures contributed to more complex responses than a consistent amplification of climate impacts of higher trophic levels. Our study provides additional insights into the ecological mechanisms that will impact marine ecosystems, thereby informing model and scenario development.

BackgroundThe left ventricular (LV) changes which occur in Friedreich ataxia (FRDA) are incompletely understood.MethodsCardiac magnetic resonance (CMR) imaging was performed using a 1.5T scanner in subjects with FRDA who are homozygous for an expansion of an intron 1 GAA repeat in the FXN gene. Standard measurements were performed of LV mass (LVM), LV end-diastolic volume (LVEDV) and LV ejection fraction (LVEF). Native T1 relaxation time and the extracellular volume fraction (ECV) were utilised as markers of left ventricular (LV) diffuse myocardial fibrosis and late gadolinium enhancement (LGE) was utilised as a marker of LV replacement fibrosis. FRDA genetic severity was assessed using the shorter FXN GAA repeat length (GAA1).ResultsThere were 93 subjects with FRDA (63 adults, 30 children, 54% males), 9 of whom had a reduced LVEF (ConclusionAn association between diffuse interstitial LV myocardial fibrosis and genetic severity in FRDA was present independently of FRDA-related LV structural changes. Localised replacement fibrosis was found in a minority of subjects with FRDA and was not associated with LV structural change or FRDA genetic severity in subjects with a normal LVEF.

BackgroundMost U.S. K-12 schools have adopted safety tactics and policies like arming teachers and installing metal detectors, to address intentional school gun violence. However, there is minimal research on their effectiveness. Furthermore, sociodemographic factors may influence their implementation. Controlled studies are necessary to investigate their impact on gun violence and related disciplinary outcomes.ObjectiveThe paper outlines the protocol for a case-control study examining gun violence prevention policies in U.S. K-12 schools. The study aims to investigate if there is an association between the total number and type of specific safety tactics and policies and the occurrence of intentional shootings in K-12 public schools, student disciplinary outcomes, and if urbanicity, economic, and racial factors modify these associations.MethodsWe will create a nationally representative dataset for this study and ascertain a full census of case schools (schools that experienced intentional gunfire on the campus during school hours since 2015) through national school shooting databases. Matched control schools will be randomly selected from U.S. Department of Education's national database of all public schools. We will analyze 27 school safety strategies organized into seven key exposure groupings.ResultsSupported by the National Institutes for Child Health and Development (R01HD108027-01) and having received Institutional Review Board approval, our study is currently in the data collection phase. Our analytical plan will determine the association between the number and type of school safety tactics and policies with the occurrence of intentional shootings and suspensions and expulsions in a national sample of approximately 650 K-12 public schools. Additional analyses will investigate the effect modification of specific covariates.ConclusionAs the first national, controlled study, its results will provide novel and needed data on the effectiveness of school safety tactics and policies in preventing intentional shootings at K-12 public schools.

BackgroundThe liking for sweet taste is a powerful driver for consuming added sugars, and therefore, understanding how sweet liking is formed is a critical step in devising strategies to lower added sugars consumption. However, current research on the influence of genetic and environmental factors on sweet liking is mostly based on research conducted with individuals of European ancestry. Whether these results can be generalized to people of other ancestry groups warrants investigation.MethodsWe will determine the differences in allele frequencies in sweet-related genetic variants and their effects on sweet liking in 426 adults of either African or East Asian ancestry, who have the highest and lowest average added sugars intake, respectively, among ancestry groups in the U.S. We will collect information on participants' sweet-liking phenotype, added sugars intake (sweetness exposure), anthropometric measures, place-of-birth, and for immigrants, duration of time living in the U.S. and age when immigrated. Ancestry-specific polygenic scores of sweet liking will be computed based on the effect sizes of the sweet-related genetic variants on the sweet-liking phenotype for each ancestry group. The predictive validity of the polygenic scores will be tested using individuals of African and East Asian ancestry from the UK Biobank. We will also compare sweet liking between U.S.-born individuals and immigrants within each ancestry group to test whether differences in environmental sweetness exposure during childhood affect sweet liking in adulthood.DiscussionExpanding genetic research on taste to individuals from ancestry groups traditionally underrepresented in such research is consistent with equity goals in sensory and nutrition science. Findings from this study will help in the development of a more personalized nutrition approach for diverse populations.Trial registrationThis protocol has been preregistered with the Center for Open Science (https://doi.org/10.17605/OSF.IO/WPR9E).

How does the riskiness of an ageing population change with house price dynamics of rural areas? Why do rural house prices increase faster than cities despite their ageing populations? Life cycle theory predicts working age households have higher demand for housing than retirement households. An issue that has seen much less attention in the literature is that rural house prices have been increasing despite their populations age rapidly. To answer these issues, our paper introduces an empirical cointegration-based framework designed to be flexible for empirical settings. Our cointegration framework reveals crucial information about rural housing and ageing which has not been found previously: the short-term deviation of house prices from cointegration restrictions is a strong predictor of future rural house prices and migration rate from 1 to 4 year ahead. This is not the case for urban areas nor where cointegration restrictions are being ignored. Rural house prices, not urban ones, are the key to understand this cointegration restriction. Our framework is pertinent to most ageing societies with available housing and demographic data. When a government formulates macroprudential policies internalizing these cointegration restrictions and supporting rural developments, migration into rural areas and population increases are possible. Our evidence highlights the importance of cointegration-based long-run ageing risks for rural housing markets.

Continued smoking among patients with chronic diseases detrimentally affects their health and treatment outcomes. However, a majority of smokers with chronic diseases appear to have no intention to quit. Understanding the needs and concerns of this population is a crucial step in facilitating the design of an appropriate smoking cessation intervention. This study aimed to understand the risk perception, behaviours, attitudes, and experiences related to smoking and smoking cessation among patients with chronic diseases, including cardiovascular diseases, chronic respiratory diseases, and/or diabetes in Hong Kong. Individual semi-structured interviews with smokers with chronic diseases (n = 30) were conducted from May to July 2021. The methods and results are reported according to the COREQ. Four themes were generated: (1) perceptions of the association between chronic diseases and smoking/smoking cessation; (2) perceptions of the health/disease status; (3) quitting smoking is not the first priority; and (4) perceived barriers to quitting smoking. This study addressed a gap in the literature by gathering data concerning the perspectives of smokers with chronic diseases on smoking and smoking cessation. The deficit of knowledge among smokers with chronic diseases warrants the reinforcement of health education targeting this population. Our findings indicate the need for further efforts in designing appropriate smoking cessation interventions targeting smokers with chronic diseases, which will match the needs and concerns identified in this study.

BackgroundA progressive approach to quitting smoking has been a popular strategy for motivating smokers who are reluctant to quit. However, whether this strategy can effectively achieve complete cessation or is as successful as quitting immediately remains unresolved. This study aimed to determine whether quitting immediately or progressively was more effective in achieving complete cessation among smokers in Hong Kong who presented at emergency departments.Methods and findingsA posteriori analysis of a single-blinded, multicenter, randomized controlled trial was performed. The original trials was conducted at emergency departments of four major acute hospitals in different districts of Hong Kong. In total, 1571 smokers 18 years or older who presented at 4 major emergency departments between July 4, 2015 and March 17, 2017 were randomized into an intervention group (n = 787) and a control group (n = 784). The intervention group received brief advice (about 1 minute) and could choose their own quit schedules (immediate or progressive, labeled QI and QP, respectively). The control group received a smoking cessation leaflet. Follow-ups were conducted at 1, 3, 6 and 12 months. The primary outcomes, by intention-to-treat, were biochemically validated abstinence between the QI subgroup and control group; between the QP subgroup and control group, and between the QI subgroup and QP subgroup at 6 months. After the propensity sore matching, the biochemically validated abstinence was statistically significantly higher in the QI subgroup than the control group at 6 months (12.1% vs 3.4%, P = 0.003; adjusted odds ratio [aOR] 4.34, 95% CI 1.63-11.52) and higher in the QP subgroup than the control group at 6 months (9.8% vs 3.4%, P = 0.02; aORs 2.95, 95% CI: 1.04-8.39). No statistically significant differences of biochemically validated abstinence at both 6 month (12.1% vs 9.8%, P = 0.49; aORs 1.50, 95% CI: 0.71-3.19) were found in the comparison between QI and QP subgroups.ConclusionsThis study demonstrates that the strategy of quitting progressively is effective, especially for smokers who lack motivation or find it difficult to quit. If adopted routinely, such an approach can help achieve a greater level of smoking abstinence in the community.Trial registrationClinicalTrials.gov: NCT02660957.

Identity-based motivation theory predicts that how sure students are of attaining their academic possible identities (possible identity certainty) interacts recursively with the inferences they make thinking about schoolwork feels hard—this is important for me (difficulty-as-importance) and this is just not for me (difficulty-as-impossibility). Recursivity implies bidirectionality across time points. To date, studies primarily from the U.S. and China only document a shift up or down from one time to a second time. We address this method gap with a three-time-point, two-month study during a secondary school transition (Chinese students N = 818, Mage = 12, 44% female). We obtained prior grades (T0) and placement test scores (T1+). Students filled out questionnaires at critical junctures: a month before the placement test (T1), the day test results were announced (T2), and after learning their school placement (T3). Across three time points, structural equation model results show bidirectional paths linking academic possible identity certainty and difficulty-as-importance beliefs. Controlling for prior grades, students higher in possible identity certainty at T1 scored higher on their placement tests at T1+. Students with higher T1+ placement test scores had higher difficulty-as-importance at T2, controlling for T1 their difficulty-as-importance score. Students with higher T2 difficulty-as-importance had higher T3 possible identity certainty, controlling for their T2 possible identity certainty score. The reverse was also true—students with higher T2 possible identity certainty had higher T3 difficulty-as-importance, controlling for their T2 difficulty-as-importance score. In contrast, controlling for prior scores, from T1 to T2 and T2 to T3 possible identity certainty and difficulty-as-impossibility were unidirectionally related. Students with higher possible identity certainty had lower difficulty-as-impossibility beliefs and not the reverse. Taken together, our results support a recursive process by which difficulty-as-importance beliefs support academic goal pursuit by bolstering students' certainty of attaining their possible identities and certainty reduces difficulty-as-impossibility beliefs. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the differential gene expression of BMPs in chick retinal pigment epithelium (RPE) during recovery from short term exposure to optical defocus and form-deprivation (FD) treatments. Methods: 14-day old White-Leghorn chicks wore either monocular +10 or -10 D lenses, or diffusers for 2 or 48 h, after which eyes were allowed unobstructed vision for up to 96 h. Over this recovery period, refractive errors and choroidal thickness (ChT) were tracked using retinoscopy and high-frequency A-scan ultrasonography. Real-time PCR was used to examine the expression of BMP2, 4, and 7 genes in RPE samples collected 0, 15 min, 2, 24, 48, and 96 h after the termination of treatments. Expression levels in treated eyes and their contralateral control eyes were compared. Results: After the termination of the lens and diffuser treatments, eyes gradually recovered from induced shifts in refractive error. With all three treatments, ChT changes reached statistical significance after 48 h of treatment, be it thinning with the -10 D lens and diffuser treatments (-0.06 ± 0.03mm, p < 0.05; -0.11 ± 0.04 mm, p < 0.05, resp.), or thickening with the +10 D lens (0.31 ± 0.04 mm, p < 0.001). BMP2 gene expression was rapidly upregulated in eyes wearing the +10 D lens, being statistical significance after 2 h, as well as 48 h of treatment. With the 2 h treatment, the latter gene expression pattern persisted for 15 min into the recovery period, before decreasing to the same level as that of contralateral control eyes, with a short-lived rebound, i.e., upregulation, 24 h into the recovery period. With the longer, 48 h treatment, BMP2 gene expression decreased more gradually, from 739 ± 121% at the end of the treatment period, to 72 ± 14% after 48 h of recovery. Two and 48 h of both -10 D and FD treatments resulted in BMP2 gene expression downregulation, with the time taken for gene expression levels to fully recover varying with the duration of initial treatments. In both cases, BMP2 gene expression downregulation persisted for 15 min into the recovery period, but reversed to upregulation by 2 h. Similar gene expression patterns were also observed for BMP4, although the changes were smaller. Conclusions: The observed changes in BMP gene expression in chick RPE imply dynamic, albeit complex regulation, with the duration of exposure and recovery being critical variables for all three types of visual manipulations. This study provides further evidence for a role of the RPE as an important signal relay linking the retina to the choroid and sclera in eye growth regulation. [ABSTRACT FROM AUTHOR]

The social context is crucial for the adolescent development of self-regulatory skills and social responsibility. To understand the role of social context in adolescent development, the present study examined family predictors (i.e., family cohesion and conflict) of social responsibility, with emotion regulation ability as a mediating process. A total of 828 Chinese adolescents (35.6% female; mean age = 13.92 years, SD = 1.34) were recruited from major Chinese cities, including Hong Kong and Macau. Path analysis revealed that emotion regulation ability mediated the relation between family factors (i.e., family cohesion and family conflict) and social responsibility. That is, the ability to regulate emotions serves as a process between family factors and social responsibility. More specifically, family cohesion was positively associated with emotion regulation ability, whereas family conflict was negatively associated with emotion regulation ability. In turn, emotion regulation ability was positively associated with social responsibility. The results suggested that the family environment and adolescent's emotion regulation ability are important contextual and intrapersonal factors contributing to their development of social responsibility. As an implication, policymakers and practitioners might allocate resources to enrich positive family interactions and cultivate emotional competency to support adolescents' development of social responsibility. [ABSTRACT FROM AUTHOR]

[This corrects the article DOI: 10.1371/journal.pone.0249052.].

Endovascular thrombectomy (EVT) is the standard of care for large vessel occlusion stroke. Use of Computed Tomographic Perfusion (CTP) to select EVT candidates is variable. The frequency of treatment and outcome in patients with unfavourable CTP patterns is unknown. A retrospective analysis of CTP utilisation prior to EVT was conducted. All CTP data were analysed centrally and a Target Mismatch was defined as an infarct core ≤70 ml, penumbral volume ≥15ml, and a total hypoperfused volume:core volume ratio >1.8. The primary outcome was good functional outcome at 90 days, defined as a modified Rankin Scale (mRS) score 0-2. follow-up infarct volume, core expansion and penumbral salvage volumes were secondary outcomes. Of 572 anterior circulation EVT patients, CTP source image data required to generate objective maps were available in 170, and a Target Mismatch was present in 151 (89%). The rate of 90-day good functional outcome was similar between Target Mismatch (53%) and Large Core Non-Mismatch groups (46%, p = 0.629). Median follow-up infarct volume in the Large Core Non-Mismatch group (104ml [IQR 25ml-189ml]) was larger than that in the Target Mismatch patients (16ml [8ml-47ml], p

IntroductionThe aim of our study was to assess the initial impact of COVID-19 on total publicly-funded direct healthcare costs and health services use in two Canadian provinces, Ontario and British Columbia (BC).MethodsThis retrospective repeated cross-sectional study used population-based administrative datasets, linked within each province, from January 1, 2018 to December 27, 2020. Interrupted time series analysis was used to estimate changes in the level and trends of weekly resource use and costs, with March 16-22, 2020 as the first pandemic week. Also, in each week of 2020, we identified cases with their first positive SARS-CoV-2 test and estimated their healthcare costs until death or December 27, 2020.ResultsThe resources with the largest level declines (95% confidence interval) in use in the first pandemic week compared to the previous week were physician services [Ontario: -43% (-49%,-37%); BC: -24% (-30%,-19%) (both pConclusionsReduced utilization of healthcare services in the overall population outweighed utilization by COVID-19 patients in 2020. Meeting the needs of all patients across all services is essential to maintain resilient healthcare systems.

IntroductionLarge language models, in particular ChatGPT, have showcased remarkable language processing capabilities. Given the substantial workload of university medical staff, this study aims to assess the quality of multiple-choice questions (MCQs) produced by ChatGPT for use in graduate medical examinations, compared to questions written by university professoriate staffs based on standard medical textbooks.Methods50 MCQs were generated by ChatGPT with reference to two standard undergraduate medical textbooks (Harrison's, and Bailey & Love's). Another 50 MCQs were drafted by two university professoriate staff using the same medical textbooks. All 100 MCQ were individually numbered, randomized and sent to five independent international assessors for MCQ quality assessment using a standardized assessment score on five assessment domains, namely, appropriateness of the question, clarity and specificity, relevance, discriminative power of alternatives, and suitability for medical graduate examination.ResultsThe total time required for ChatGPT to create the 50 questions was 20 minutes 25 seconds, while it took two human examiners a total of 211 minutes 33 seconds to draft the 50 questions. When a comparison of the mean score was made between the questions constructed by A.I. with those drafted by humans, only in the relevance domain that the A.I. was inferior to humans (A.I.: 7.56 +/- 0.94 vs human: 7.88 +/- 0.52; p = 0.04). There was no significant difference in question quality between questions drafted by A.I. versus humans, in the total assessment score as well as in other domains. Questions generated by A.I. yielded a wider range of scores, while those created by humans were consistent and within a narrower range.ConclusionChatGPT has the potential to generate comparable-quality MCQs for medical graduate examinations within a significantly shorter time.

Marine animal biomass is expected to decrease in the 21st century due to climate driven changes in ocean environmental conditions. Previous studies suggest that the magnitude of the decline in primary production on apex predators could be amplified through the trophodynamics of marine food webs, leading to larger decreases in the biomass of predators relative to the decrease in primary production, a mechanism called trophic amplification. We compared relative changes in producer and consumer biomass or production in the global ocean to assess the extent of trophic amplification. We used simulations from nine marine ecosystem models (MEMs) from the Fisheries and Marine Ecosystem Models Intercomparison Project forced by two Earth System Models under the high greenhouse gas emissions Shared Socioeconomic Pathways (SSP5-8.5) and a scenario of no fishing. Globally, total consumer biomass is projected to decrease by 16.7 ± 9.5% more than net primary production (NPP) by 2090-2099 relative to 1995-2014, with substantial variations among MEMs and regions. Total consumer biomass is projected to decrease almost everywhere in the ocean (80% of the world's oceans) in the model ensemble. In 40% of the world's oceans, consumer biomass was projected to decrease more than NPP. Additionally, in another 36% of the world's oceans consumer biomass is expected to decrease even as projected NPP increases. By analysing the biomass response within food webs in available MEMs, we found that model parameters and structures contributed to more complex responses than a consistent amplification of climate impacts of higher trophic levels. Our study provides additional insights into the ecological mechanisms that will impact marine ecosystems, thereby informing model and scenario development.

The desire to have offspring of a specific sex has a long history but has been particularly present with the appearance of assisted reproduction. However, embryo selection raises ethical concerns. Thus, several techniques to select sex-specific spermatozoa have been proposed but carry limitations. There are many variations of each technique, and some are time consuming and costly. Concerns about effectiveness and safety have also rendered many of them unappealing. Therefore, we propose a novel sperm sex selection technique (SST) that appears to be consistently safe and effective. A single-center, non-randomized clinical trial was designed. We included 1,317 couples, who were assigned to one of two groups: ICSI/PGTA or ICSI/PGTA+GS. Ejaculates from male partners of couples in the ICSI/PGTA+GS group (n = 105) were processed using SST to enrich spermatozoa for their desired sex. Standard sperm processing was carried out for couples undergoing PGT-A solely for aneuploidy (n = 1,212), comprising the ICSI/PGTA control group. To validate the efficacy of our technique, we performed an analysis on spermatozoa pre- and post-selection, followed by an assessment of the proportion of the conceptuses’ sex to confirm clinical reliability. We also followed up on ICSI clinical outcomes and child/newborn health to establish the safety of our method. Our main outcome measures included the proportion of spermatozoa and embryos enriched for female and male sex, as well as embryo euploidy rates and ICSI clinical outcomes. These outcomes were compared between the two groups. For the ICSI/PGTA group (n = 1,212) (maternal age, 37.0±4yrs; paternal age, 39.1±6yrs), with ejaculated spermatozoa processed in the standard fashion, 2,303 ICSI cycles (1.2±1) yielded an 81.0% (14,375/17,737) fertilization. PGT-A results indicated a euploidy rate of 73.1% (n = 3,718) for female and 72.4% (n = 3,054) for male embryos. These couples achieved a 76.4% (699/915) implantation and 65.2% (597/915) clinical pregnancy rate, with 551 deliveries (48.5% female, 51.5% male). All 105 men in the ICSI/PGTA+GS group had sperm specimens with an equal sex distribution at baseline. Of them, 59 (paternal age, 40.9±6yrs) who desired female offspring obtained an 81.6% enrichment after SST. They underwent 73 ICSI cycles with their partners (maternal age, 37.9±4yrs), achieving a 77.3% (583/754) fertilization. This resulted in 79.1% (231/292) female embryos that generated a 79.3% (23/29) implantation rate, with 16 singleton deliveries of the desired female sex without major or minor congenital malformations. Forty-six couples (maternal age, 37.3±4yrs; paternal age, 40.7±6yrs) desiring male offspring obtained an 80.8% sperm sex enrichment. They underwent 50 ICSI cycles, achieving a 75.4% (462/613) fertilization and equivalent proportion of male embryos (223/280, 79.6%). Their implantation was 90.5% (19/21), with 13 singleton deliveries of healthy male offspring. Furthermore, 78.8% (182/231) of female and 66.4% (148/223) of male embryos from the ICSI/PGTA+GS cohort were euploid. These euploid rates were comparable to those from the ICSI/PGTA group. In couples undergoing ICSI with PGT-A, SST consistently enriched spermatozoa, resulting in a higher proportion of embryos and thus offspring of the desired sex. Moreover, SST did not impair the fertilization or embryo developmental competence of spermatozoa, nor did it affect offspring health. Trial registration: Clinicaltrials.gov NCT05500573.

Pediatric population was generally less affected clinically by SARS-CoV-2 infection. Few pediatric cases of COVID-19 have been reported compared to those reported in infected adults. However, a rapid increase in the hospitalization rate of SARS-CoV-2 infected pediatric patients was observed during Omicron variant dominated COVID-19 outbreak. In this study, we analyzed the B.1.1.529 (Omicron) genome sequences collected from pediatric patients by whole viral genome amplicon sequencing using Illumina next generation sequencing platform, followed by phylogenetic analysis. The demographic, epidemiologic and clinical data of these pediatric patients are also reported in this study. Fever, cough, running nose, sore throat and vomiting were the more commonly reported symptoms in children infected by Omicron variant. A novel frameshift mutation was found in the ORF1b region (NSP12) of the genome of Omicron variant. Seven mutations were identified in the target regions of the WHO listed SARS-CoV-2 primers and probes. On protein level, eighty-three amino acid substitutions and fifteen amino acid deletions were identified. Our results indicate that asymptomatic infection and transmission among children infected by Omicron subvariants BA.2.2 and BA.2.10.1 are not common. Omicron may have different pathogenesis in pediatric population.

Adolescent idiopathic scoliosis (AIS) disrupts spinal alignment and increases the intrinsic demand for active stabilization to maintain postural stability. Understanding the paraspinal muscle fatigability and its effects on spinal alignment and kinematics informs the importance of paraspinal muscle endurance for postural stability. This study aims to investigate the effects of fatigue of thoracic erector spinae on the spinal muscle activity and spinal kinematics in individuals with scoliosis. Spinal muscle activity, posture and mobility measured by electromyography and surface tomography were compared between 15 participants with scoliosis and 15 age- and gender-matched healthy controls during unilateral shoulder flexion and abduction with and without holding a 2-kg weight and performed before and after a fatigue task (prone isometric chest raise). No between-groups difference was found for the spinal extensor endurance. Erector spinae activity at the convex side of AIS group was significantly higher than that at their concave side and than that of healthy controls during shoulder elevations, regardless of the fatigue status. Significant decreases in translational and rotational mobility were found at convex side of AIS group during weighted abduction tasks after fatigue. In contrast, a significant increase in rotational mobility was demonstrated at convex side of AIS participants during weighted flexion tasks after fatigue. Our results revealed a comparable level of spinal extensor endurance between individuals with or without AIS. The increase in muscle activation post-fatigue provides no additional active postural stability but may increase the risk of back pain over the convex side in individuals with scoliosis. Findings highlight imbalances in muscles and the potential implications in optimising neuromuscular activation and endurance capacity in the rehabilitation for AIS patients. Future research is needed to investigate if endurance training of the convex-sided back extensors could optimize the impaired neuromuscular control in the AIS patients.

IntroductionAcute traumatic coagulopathy has been associated with shock and tissue injury, and may be mediated via activation of the protein C pathway. Patients with acute traumatic coagulopathy have prolonged PT and PTT, and decreased activity of factors V and VIII; they are also hypocoagulable by thromboelastometry (ROTEM) and other viscoelastic assays. To test the etiology of this phenomenon, we hypothesized that such coagulopathy could be induced in vitro in healthy human blood with the addition of activated protein C (aPC).MethodsWhole blood was collected from 20 healthy human subjects, and was "spiked" with increasing concentrations of purified human aPC (control, 75, 300, 2000 ng/mL). PT/PTT, factor activity assays, and ROTEM were performed on each sample. Mixed effect regression modeling was performed to assess the association of aPC concentration with PT/PTT, factor activity, and ROTEM parameters.ResultsIn all subjects, increasing concentrations of aPC produced ROTEM tracings consistent with traumatic coagulopathy. ROTEM EXTEM parameters differed significantly by aPC concentration, with stepwise prolongation of clotting time (CT) and clot formation time (CFT), decreased alpha angle (α), impaired early clot formation (a10 and a20), and reduced maximum clot firmness (MCF). PT and PTT were significantly prolonged at higher aPC concentrations, with corresponding significant decreases in factor V and VIII activity.ConclusionA phenotype of acute traumatic coagulopathy can be induced in healthy blood by the in vitro addition of aPC alone, as evidenced by viscoelastic measures and confirmed by conventional coagulation assays and factor activity. This may lend further mechanistic insight to the etiology of coagulation abnormalities in trauma, supporting the central role of the protein C pathway. Our findings also represent a model for future investigations in the diagnosis and treatment of acute traumatic coagulopathy.

IntroductionAdvances in health technology such as genome sequencing and wearable sensors now allow for the collection of highly granular personal health data from individuals. It is unclear how people think about privacy in the context of these emerging health technologies. An open question is whether early adopters of these advances conceptualize privacy in different ways than non-early adopters.PurposeThis study sought to understand privacy attitudes of early adopters of emerging health technologies.MethodsTranscripts from in-depth, semi-structured interviews with early adopters of genome sequencing and health devices and apps were analyzed with a focus on participant attitudes and perceptions of privacy. Themes were extracted using inductive content analysis.ResultsAlthough interviewees were willing to share personal data to support scientific advancements, they still expressed concerns, as well as uncertainty about who has access to their data, and for what purpose. In short, they were not dismissive of privacy risks. Key privacy-related findings are organized into four themes as follows: first, personal data privacy; second, control over personal information; third, concerns about discrimination; and fourth, contributing personal data to science.ConclusionEarly adopters of emerging health technologies appear to have more complex and nuanced conceptions of privacy than might be expected based on their adoption of personal health technologies and participation in open science. Early adopters also voiced uncertainty about the privacy implications of their decisions to use new technologies and share their data for research. Though not representative of the general public, studies of early adopters can provide important insights into evolving attitudes toward privacy in the context of emerging health technologies and personal health data research.

Background/objectivesMost of the studies on functional outcomes in pediatric survivors of cancers and bone marrow failure disorders have been conducted in North American, European, and Oceanian populations, with few studies having been performed in China. The objective of this study was to evaluate psychosocial outcomes in a cohort of Chinese pediatric survivors diagnosed with cancer or conditions requiring hematopoietic stem cell transplantation (HSCT), and to identify clinical and behavioral factors associated with adverse psychosocial outcomes.MethodsThis was a cross-sectional survey study. We recruited pediatric survivors of cancer or inherited disorder requiring HSCT at ≤18 years old and were ≥6 months post-treatment. Parents completed the St. Jude Children's Research Hospital After Completion of Therapy questionnaire to report their child's emotional functioning, social functioning, attention/concentration and behavior. Multivariable general linear modeling was used to identify clinical, treatment and behavioral factors associated with psychosocial outcomes, adjusting for sex, age and cancer diagnoses.ResultsNinety-five pediatric survivors were recruited (62.1% male; mean [standard deviation] age 9.7 [3.4] years; 4.1 [2.6] years post-diagnosis). They were diagnosed with bone marrow failure disorders (23.2%), hematological malignancies (45.3%) or solid tumors (23.2%). Compared with survivors with no current health problems, those with more than one current health problem performed worse in emotional functioning (Estimate = 2.42, SE = 0.88, P = 0.008) and social functioning (Estimate = 2.90, SE = 1.64, P = 0.03). Higher pain interference was significantly associated with worse emotional functioning (Estimate = 0.19, SE = 0.08, P = 0.03) and attention functioning (Estimate = 0.26, SE = 0.11, P = 0.03). Compared with survivors who reported less sleep problems, those who had more sleep problems demonstrated poorer emotional functioning (Estimate = 0.30, SE = 0.08, P = 0.001). Survivors who had a longer duration of screen usage per day reported more impairment on attention and behavior functioning than those who had a shorter duration of screen usage per day (both PConclusionSurvivors who were diagnosed at a younger age or had unaddressed/untreated health problems may require additional psychological evaluation. The implementation of psychosocial assessments during routine long-term follow-up care may help to identify high-risk patients during the early phase of survivorship. Rehabilitation interventions should address modifiable behavioral factors (e.g. sleep habits, screen time and chronic pain).

Chronic hepatitis B (CHB) is a global health care challenge and a major cause of liver disease. To find new therapeutic avenues with a potential to functionally cure chronic Hepatitis B virus (HBV) infection, we performed a focused screen of epigenetic modifiers to identify potential inhibitors of replication or gene expression. From this work we identified isonicotinic acid inhibitors of the histone lysine demethylase 5 (KDM5) with potent anti-HBV activity. To enhance the cellular permeability and liver accumulation of the most potent KDM5 inhibitor identified (GS-080) an ester prodrug was developed (GS-5801) that resulted in improved bioavailability and liver exposure as well as an increased H3K4me3:H3 ratio on chromatin. GS-5801 treatment of HBV-infected primary human hepatocytes reduced the levels of HBV RNA, DNA and antigen. Evaluation of GS-5801 antiviral activity in a humanized mouse model of HBV infection, however, did not result in antiviral efficacy, despite achieving pharmacodynamic levels of H3K4me3:H3 predicted to be efficacious from the in vitro model. Here we discuss potential reasons for the disconnect between in vitro and in vivo efficacy, which highlight the translational difficulties of epigenetic targets for viral diseases.

IntroductionYoung adults are considered one of the most hesitant groups towards getting vaccinated in the UK, which threatens the success of the vaccination program in ending the pandemic. Identifying and understanding the socio-cognitive beliefs is important to effectively design and implement health communication interventions. Therefore, the aim of this study was to identify the underlying beliefs regarding COVID-19 vaccinations among young adults in the UK.MethodsThe study consisted of online, one-on-one interviews with 18 individuals (6 males, 12 females) aged between 18 and 29 years, conducted in June 2021. The guiding theoretical framework was the I-Change Model. Interviews were recorded and transcribed verbatim. The transcripts were independently coded by two researchers by using the constructs of the I-Change Model. Belief statements were elicited from the codes and the frequency of belief statements was recorded and compared between intenders and non-intenders.ResultsSimilar beliefs were observed in intenders and non-intenders for most constructs of the I-Change Model. However, non-intenders distinguished themselves from intenders by their higher perceived risks of side effects and higher perceived disadvantages of being vaccinated. Non-intenders expressed the belief that the risk of unknown or long-term side effects, such as blood clotting and impact on fertility, were the main reason for them not to be willing to vaccinate. In addition, in both groups, participants had mostly similar beliefs as their friends and family.ConclusionThis research provides insights in the specific beliefs of the young adult population of the UK regarding COVID-19 vaccinations, which could have implications for health communication interventions. The findings suggest that such interventions should focus on reducing the uncertainty regarding short- and long-term effects and potentially having a focus on the entire social environment of young adults.

[This corrects the article DOI: 10.1371/journal.pone.0122592.].

Background The clinical implementation of pharmacogenomics (PGx) could be one of the first milestones towards realizing personalized medicine in routine care. However, its widespread adoption requires the availability of suitable clinical decision support (CDS) systems, which is often impeded by the fragmentation or absence of adequate health IT infrastructures. We report results of CDS implementation in the large-scale European research project Ubiquitous Pharmacogenomics (U-PGx), in which PGx CDS was rolled out and evaluated across more than 15 clinical sites in the Netherlands, Spain, Slovenia, Italy, Greece, United Kingdom and Austria, covering a wide variety of healthcare settings. Methods We evaluated the CDS implementation process through qualitative and quantitative process indicators. Quantitative indicators included statistics on generated PGx reports, median time from sampled upload until report delivery and statistics on report retrievals via the mobile-based CDS tool. Adoption of different CDS tools, uptake and usability were further investigated through a user survey among healthcare providers. Results of a risk assessment conducted prior to the implementation process were retrospectively analyzed and compared to actual encountered difficulties and their impact. Results As of March 2021, personalized PGx reports were produced from 6884 genotyped samples with a median delivery time of twenty minutes. Out of 131 invited healthcare providers, 65 completed the questionnaire (response rate: 49.6%). Overall satisfaction rates with the different CDS tools varied between 63.6% and 85.2% per tool. Delays in implementation were caused by challenges including institutional factors and complexities in the development of required tools and reference data resources, such as genotype-phenotype mappings. Conclusions We demonstrated the feasibility of implementing a standardized PGx decision support solution in a multinational, multi-language and multi-center setting. Remaining challenges for future wide-scale roll-out include the harmonization of existing PGx information in guidelines and drug labels, the need for strategies to lower the barrier of PGx CDS adoption for healthcare institutions and providers, and easier compliance with regulatory and legal frameworks.

A recent consensus guideline recommends migrating the therapeutic drug monitoring practice for intravenous vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infection from the traditional trough-based approach to the Bayesian approach based on area under curve to improve clinical outcomes. To support the implementation of the new strategy for hospitals under Hospital Authority, Hong Kong, this study is being proposed to (1) estimate and validate a population pharmacokinetic model of intravenous vancomycin for local adults, (2) develop a web-based individual dose optimization application for clinical use, and (3) evaluate the performance of the application by comparing the treatment outcomes and clinical satisfaction against the traditional approach. 300 adult subjects prescribed with intravenous vancomycin and not on renal replacement therapy will be recruited for population pharmacokinetic model development and validation. Sex, age, body weight, serum creatinine level, intravenous vancomycin dosing records, serum vancomycin concentrations etc. will be collected from several electronic health record systems maintained by Hospital Authority. Parameter estimation will be performed using non-linear mixed-effect modeling techniques. The web-based individual dose optimization application is based on a previously reported application and is built using R and the package shiny. Data from another 50 subjects will be collected during the last three months of the study period and treated as informed by the developed application and compared against historical control for clinical outcomes. Since the study will incur extra blood-taking procedures from patients, informed consent is required. Other than that, recruited subjects should receive medical treatments as usual. Identifiable patient data will be available only to site investigators and clinicians in each hospital. The study protocol and informed consent forms have been approved by the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (reference number: NTEC-2021-0215) and registered at the Chinese Clinical Trial Registry (registration number: ChiCTR2100048714).

Patients with cystic fibrosis (CF) often suffer recurrent bronchial bacterial infections that lead to deterioration of lung function over time. The infections in CF patients are often due to S. aureus and P. aeruginosa that colonize the airways. Significantly, methicillin-resistant S. aureus (MRSA) makes it challenging for treatment in CF patients due to its feature of multiple antibiotic resistance. In bronchial airways, cationic antimicrobial peptides are often present in mucosa cells, neutrophils, and macrophages that interfere with bacterial proliferation. The major mechanism for resistance to the bactericidal activity of cationic peptides in S. aureus is mediated by the GraRS two-component system that activates expression of MprF and DltABCD to increase surface positive charge to repel interactions with cationic peptides. We recently found that VraG, a membrane permease component of the VraFG efflux pumps, harbors a long 200-residue extracellular loop (EL) that utilizes K380 to interact with the negatively charged 9-residue extracellular loop of the membrane sensor GraS to control mprF expression in a community-acquired MRSA strain JE2. In this study, we extended this observation to a CF MRSA strain CF32A1 where we affirmed that the EL loop of VraG controls GraS-mediated signal transduction; however, in contrast to community acquired MRSA strain JE2, the CF MRSA strain CF32A1 requires both K380 and K388 in the EL of VraG to properly modulate signal transduction mediated by GraS. This effect was not attributable to the several single nucleotide polymorphisms that exist between VraG and GraS in the two MRSA strains.

Purpose(1) To investigate the relative importance of convenience (consultation frequency and injection frequency) against treatment outcomes (visual and anatomical outcomes) and out-of-pocket medical costs via a discrete choice experiment (DCE), and (2) to investigate how patient characteristics affect patient treatment preferences.MethodsEligibility criteria were: (1) receiving a neovascular age-related macular degeneration (nAMD) diagnosis; (2) receiving anti-VEGF treatment; (3) being ≥21 years old, and (4) being able to speak and understand English/Mandarin. Patients were presented with eight choice tasks and asked to choose between their current treatment and two hypothetical treatments that varied by six attributes: number of clinic visits in a year, number of injections in a year, vision quality, control of swelling in retina, drug labelling and out-of-pocket cost.ResultsThis analysis involved 180 patients. Based on latent class logistic regressions, vision quality was the most important attribute (34%) followed by cost (24%). The frequency of total clinic visits (15%) was the third most-important attribute, closely followed by labelling (12%) and control of retina swelling (11%). Injection frequency was the least important attribute (4%).ConclusionsVision quality was the most important attribute followed by the out-of-pocket costs. Given the same outcomes, patients preferred treatment regimens which require fewer total clinic visits. In comparison, injection frequency alone did not influence patient preferences. With increasing treatment options for nAMD, understanding patients' preferences can help clinicians in selecting agents and treatment regimen most preferred for each patient, which may lead to improved long-term adherence and outcomes.

In Australia, research evidence has shown that Aboriginal and/or Torres Strait Islander children experience a higher burden of oral health diseases compared to other non-Indigenous children. The impact of oral health diseases on children's functional and psychosocial outcomes led to the development of several instruments to evaluate child oral health-related quality of life (COHQoL), such as the Parental-Caregiver Perception Questionnaire (P-CPQ) and the Family Impact Scale (FIS). However, the psychometric properties of these instruments have been evaluated only in Western cultures and have not been investigated for Aboriginal children in Australia. The current study aimed to examine the psychometric properties of the short-forms P-CPQ and FIS for Aboriginal and/or Torres Strait Islander children aged 2-3 years. Data were collected from the South Australian Aboriginal Birth Cohort (SAABC), including 270 Aboriginal children aged 2-3 years. Network psychometric models were used to investigate dimensionality, item redundancy, structural consistency and item stability, model fit, internal consistency reliability and criterion validity. We propose an instrument named Aboriginal Children's Oral Health-Related Quality of Life Questionnaire (A-COHQoL). Our findings indicated that, after the exclusion of four problematic items, the A-COHQoL showed a three-dimensional structure ("Parent/Family Activities", "COHQoL" and "Family Conflict") with good model fit and reliability. The A-COHQoL is a psychometrically robust and sensitive instrument that is readily available for Aboriginal and/or Torres Strait Islander children aged 2-3 years in Australia and can be adapted in the future for Indigenous child groups in other countries.

Attitudes toward aggression is a controversial phenomenon in psychiatry. This study examined and compared attitudes toward patient aggression in psychiatric hospitals from the perspectives of nurses, patients and informal caregivers and identified factors associated to these attitudes. A total of 2,424 participants completed a self-reported instrument regarding attitudes toward aggression (12-items Perception of Aggression Scale; POAS-S). We analysed data from nurses (n = 782), patients (n = 886), and informal caregivers (n = 765). Pearson's r correlations were used to examine associations between variables. Differences between group scores were analysed using ANOVA/MANOVA with post-hoc Sheffe tests. Multivariate logistic regression models and logistic regression analysis were used to examine the effects of respondents' characteristics on their attitudes toward aggression. Nurses had significantly more negative and less tolerant perceptions toward aggression (mean [SD] 47.1 [7.5], p

High-risk human papillomavirus (HR-HPV) testing has become an increasing important strategy in primary cervical cancer screening in recent years. It warrants the evaluation of molecular-based HPV tests for accuracy and efficacy of screening. The performance of Roche Cobas 4800 HPV test was validated and compared with Digene Hybrid Capture 2 (HC2) high-risk HPV DNA test for primary screening in a large Chinese screening cohort. Of 6345 women screened, overall agreement between Cobas and HC2 was 92.23% (95% CI: 91.57-92.89). The inter-assay agreement was correlated with the severity of underlying biology, with an increasing concordance found in samples with more severe abnormalities. Most of the discordant samples had the test signal strength closer to the test limits of the detection than concordant samples, reflecting a low viral load and infection of a cluster of low-risk HPV in these samples. The Cobas test demonstrated significantly higher specificity in identifying CIN2+/CIN3+ cases than HC2 test (66.46% vs 43.67% and 65.42% vs 42.86%, p

IntroductionVision is critical for children's development. However, prevalence of visual impairment (VI) is high in students with special educational needs (SEN). Other than VI, SEN students are prone to having functional deficits. Whether visual problems relate to these functional deficits is unclear. This study aimed to assess the impact of vision on visual processing functions and balance in SEN students through a community service.MethodsVisual acuity (VA) and contrast sensitivity were measured in a total of 104 (aged 14.3±4.3) SEN students as the visual outcomes, followed by retinoscopy. Visual processing function assessment included facial expression recognition by card matching examiner's facial expression matching, and visual orientation recognition. Dynamic balance, by Timed Up and Go test, and static standing balance (postural sway in double-legged standing with feet-together and tandem-stance for open-eye and closed-eye conditions) were assessed. Static balance was presented in terms of the maximal medial-lateral and antero-posterior sways.ResultsOf the 104 students, 62 (59.6%) were classified as visually impaired according to WHO classification of visual impairment based on presenting distance acuity. Ocular problems (e.g. optic nerve anomaly, uncorrected/ under-corrected refractive errors) and neurological anomalies were the major causes of vision loss. VA was positively associated with visual processing functions (all p ≤ 0.01), as SEN students with better vision tended to perform better in visual orientation and facial expression recognition tasks, as well as dynamic balance function (p = 0.04). For the static balance, postural sway and VA showed a positive relationship under open-eye and tandem stance conditions. However, the relationship between postural sway and VA became negative under closed-eye and tandem stance conditions.ConclusionThis study found a high prevalence of SEN students with visual impairment, in which many of them were undetected. Optometric examination is important to improve their visual function to minimize the effect of vision on functional performance. Vision is critical in visual processing as well as playing an important role in maintaining balance in SEN students.

BackgroundCurrent clinical evidence suggests that a well-planned physiotherapeutic scoliosis specific exercise (PSSE) program is effective for scoliosis regression.ObjectivesWe investigated the effect of curve patterns on Cobb angles with PSSE.MethodsThis was a non-randomized prospective clinical trial that recruited participants with adolescent idiopathic scoliosis between January and June 2017. Participants were grouped by curve pattern into major thoracic and major lumbar groups. An outpatient-based PSSE program was conducted with the following schedule of intensive exercise: ≥ 1 session of supervised PSSE per month and > 30min of home exercise 5 days/week in the first 6 months, after which exercise frequency was reduced to 1 session of supervised PSSE every three months and > 30min of home exercise 5 days/week until 2 years after study initiation. Radiographic Cobb angle progressions were identified at the 1, 1.5 and 2-year follow-ups. A mixed model analysis of variance (ANOVA) was performed to examine the differences in Cobb angles between groups at four testing time points. The two-tailed significance level was set to 0.05.ResultsIn total, 40 participants were recruited, including 22 with major thoracic curves (5 males and 17 females; mean age 13.5±1.8 years; Cobb angle 18-45 degrees) and 18 with major lumbar curves (7 males and 11 females; mean age 12.7±1.7 years; Cobb angle 15-48 degrees). Curve regressions, namely the reduction of Cobb angles between 7 to 10 degrees were noted in 9.1% of participants in the major thoracic group; reductions of 6 to 13 degrees were noted in 33.3% of participants in the major lumbar group at the 2-year follow-up. Repeated measurements revealed a significant time effect (F2.2,79.8 = 4.1, p = 0.02), but no group (F2.2,79.8 = 2.3, p = 0.1) or time × group (F1,37 = 0.97, p = 0.3) effects in reducing Cobb angles after 2 years of PSSE. A logistic regression analysis revealed that no correlation was observed between curve pattern and curve regression or stabilization (OR: 0.2, 95% CI: 0.31-1.1, p = 0.068) at the 2-year follow-up.ConclusionThis was the first study to investigate the long-term effects of PSSE in reducing Cobb angles on the basis of major curve location. No significant differences in correction were observed between major thoracic and major lumbar curves. A regression effect and no curve deterioration were noted in both groups at the 2-year follow-up.Trial registrationChiCTR1900028073.

ObjectivesTo assess the success of a human papillomavirus (HPV) vaccination program among adolescent girls aged 9-14 years in Haiti and to understand predictors of completion of a two-dose HPV vaccination series.MethodsData collection was conducted during HPV vaccination campaigns in Port-au-Prince between August 2016 and April 2017. Descriptive statistics and logistic regression models were used to examine characteristics associated with vaccination series completion of school based and non-school based vaccination delivery modalities.ResultsOf the 2,445 adolescent girls who participated in the awareness program, 1,994 participants (1,307 in non-school program, 687 in school program) received the first dose of the vaccine; 1,199 (92%) in the non-school program and 673 (98%) in the school program also received the second dose. Menarche (OR: 1.87; 95% CI, 1.11-3.14), if the participant was a prior patient at the GHESKIO clinics (OR: 2.17; 95% CI, 1.32-3.58), and participating in the school-based program (OR: 4.17; 95% CI, 2.14-8.12) were significantly associated with vaccination completion.ConclusionsVaccination in school- and non-school-based settings was successful, suggesting that a nationwide HPV vaccination campaign using either approach would be successful using either approach.

Reduced exercise capacity is common in people with chronic obstructive pulmonary diseases (COPD) and chronic smokers and is suggested to be related to skeletal muscle dysfunction. Previous studies using human muscle biopsies have shown fiber-type shifting in chronic smokers particularly those with COPD. These results, however, are confounded with aging effects because people with COPD tend to be older. In the present study, we implemented an acute 7-day cigarette smoke-exposed model using Sprague-Dawley rats to evaluate early effects of cigarette smoking on soleus muscles. Rats (n = 5 per group) were randomly assigned to either a sham air (SA) or cigarette smoking (CS) groups of three different concentrations of total particulate matters (TPM) (CSTPM2.5, CSTPM5, CSTPM10). Significantly lower percentages of type I and higher type IIa fiber were detected in the soleus muscle in CS groups when compared with SA group. Of these, only CSTMP10 group exhibited significantly lower citrate synthase activity and higher muscle tumor necrosis factor-α level than that of SA group. Tumor necrosis factor-α level was correlated with the percentage of type I and IIa fibers. However, no significant between-group differences were found in fiber cross-sectional area, physical activities, or lung function assessments. In conclusion, acute smoking may directly trigger the onset of glycolytic fiber type shift in skeletal muscle independent of aging.

BackgroundInternal medicine fellowship programs have an incentive to select fellows who will ultimately publish. Whether an applicant's publication record predicts long term publishing remains unknown.MethodsUsing records of fellowship bound internal medicine residents, we analyzed whether publications at time of fellowship application predict publications more than 3 years (2 years into fellowship) and up to 7 years after fellowship match. We calculate the sensitivity, specificity, positive and negative predictive values and likelihood ratios for every cutoff number of application publications, and plot a receiver operator characteristic curve of this test.ResultsOf 307 fellowship bound residents, 126 (41%) published at least one article 3 to 7 years after matching, and 181 (59%) of residents do not publish in this time period. The area under the receiver operator characteristic curve is 0.59. No cutoff value for application publications possessed adequate test characteristics.ConclusionThe number of publications an applicant has at time of fellowship application is a poor predictor of who publishes in the long term. These findings do not validate the practice of using application publications as a tool for selecting fellows.

ObjectiveDue to its anti-oxidant and anti-inflammatory properties, bilirubin has been associated with reduced cardiovascular risk. A recent study demonstrated an L-shaped association of pre-treatment total bilirubin levels with total mortality in a statin-treated cohort. We therefore investigated the association of total bilirubin levels with total mortality in a nationally representative sample of older adults from the general population.MethodsA total of 4,303 participants aged ≥ 60 years from the United States National Health and Nutrition Examination Survey 1999-2004 with mortality data followed up through December 31, 2006 were included in this analysis, with a mean follow-up period of 4.5 years.ResultsParticipants with total bilirubin levels of 0.1-0.4 mg/dl had the highest mortality rate (19.8%). Compared with participants with total bilirubin levels of 0.5-0.7 mg/dl and in a multivariable regression model, a lower total bilirubin level of 0.1-0.4 mg/dl was associated with higher risk of total mortality (hazard ratios, 1.36; 95% confidence interval, 1.07-1.72; P = 0.012), while higher levels (≥ 0.8 mg/dl) also tended to be associated with higher risk of total mortality, but this did not reach statistical significance (hazard ratios, 1.24; 95% confidence interval, 0.98-1.56; P = 0.072).ConclusionIn this nationally representative sample of older adults, the association of total bilirubin levels with total mortality was the highest among those with a level between 0.1 and 0.4 mg/dl. Further studies are needed to investigate whether higher total bilirubin levels could be associated with a higher mortality risk, compared to a level of 0.5-0.7 mg/dl.

BackgroundSickle cell anemia is an inherited disorder of hemoglobin that leads to a variety of acute and chronic complications. Abnormal cellular adhesion, mediated in part by selectins, has been implicated in the pathophysiology of the vaso-occlusion seen in sickle cell anemia, and selectin inhibition was able to restore blood flow in a mouse model of sickle cell disease.MethodsWe performed a Phase 1 study of the selectin inhibitor GMI 1070 in patients with sickle cell anemia. Fifteen patients who were clinically stable received GMI 1070 in two infusions.ResultsThe drug was well tolerated without significant adverse events. There was a modest increase in total peripheral white blood cell count without clinical symptoms. Plasma concentrations were well-described by a two-compartment model with an elimination T1/2 of 7.7 hours and CLr of 19.6 mL/hour/kg. Computer-assisted intravital microscopy showed transient increases in red blood cell velocity in 3 of the 4 patients studied.ConclusionsGMI 1070 was safe in stable patients with sickle cell anemia, and there was suggestion of increased blood flow in a subset of patients. At some time points between 4 and 48 hours after treatment with GMI 1070, there were significant decreases in biomarkers of endothelial activation (sE-selectin, sP-selectin, sICAM), leukocyte activation (MAC-1, LFA-1, PM aggregates) and the coagulation cascade (tissue factor, thrombin-antithrombin complexes). Development of GMI 1070 for the treatment of acute vaso-occlusive crisis is ongoing.Trial registrationClinicalTrials.gov NCT00911495.

Background: The left ventricular (LV) changes which occur in Friedreich ataxia (FRDA) are incompletely understood. Methods: Cardiac magnetic resonance (CMR) imaging was performed using a 1.5T scanner in subjects with FRDA who are homozygous for an expansion of an intron 1 GAA repeat in the FXN gene. Standard measurements were performed of LV mass (LVM), LV end-diastolic volume (LVEDV) and LV ejection fraction (LVEF). Native T1 relaxation time and the extracellular volume fraction (ECV) were utilised as markers of left ventricular (LV) diffuse myocardial fibrosis and late gadolinium enhancement (LGE) was utilised as a marker of LV replacement fibrosis. FRDA genetic severity was assessed using the shorter FXN GAA repeat length (GAA1). Results: There were 93 subjects with FRDA (63 adults, 30 children, 54% males), 9 of whom had a reduced LVEF (<55%). A LVEDV below the normal range was present in 39%, a LVM above the normal range in 22%, and an increased LVM/LVEDV ratio in 89% subjects. In adults with a normal LVEF, there was an independent positive correlation of LVM with GAA1, and a negative correlation with age, but no similar relationships were seen in children. GAA1 was positively correlated with native T1 time in both adults and children, and with ECV in adults, all these associations independent of LVM and LVEDV. LGE was present in 21% of subjects, including both adults and children, and subjects with and without a reduced LVEF. None of GAA1, LVM or LVEDV were predictors of LGE. Conclusion: An association between diffuse interstitial LV myocardial fibrosis and genetic severity in FRDA was present independently of FRDA-related LV structural changes. Localised replacement fibrosis was found in a minority of subjects with FRDA and was not associated with LV structural change or FRDA genetic severity in subjects with a normal LVEF. [ABSTRACT FROM AUTHOR]

Background: Most U.S. K-12 schools have adopted safety tactics and policies like arming teachers and installing metal detectors, to address intentional school gun violence. However, there is minimal research on their effectiveness. Furthermore, sociodemographic factors may influence their implementation. Controlled studies are necessary to investigate their impact on gun violence and related disciplinary outcomes. Objective: The paper outlines the protocol for a case-control study examining gun violence prevention policies in U.S. K-12 schools. The study aims to investigate if there is an association between the total number and type of specific safety tactics and policies and the occurrence of intentional shootings in K-12 public schools, student disciplinary outcomes, and if urbanicity, economic, and racial factors modify these associations. Methods: We will create a nationally representative dataset for this study and ascertain a full census of case schools (schools that experienced intentional gunfire on the campus during school hours since 2015) through national school shooting databases. Matched control schools will be randomly selected from U.S. Department of Education's national database of all public schools. We will analyze 27 school safety strategies organized into seven key exposure groupings. Results: Supported by the National Institutes for Child Health and Development (R01HD108027-01) and having received Institutional Review Board approval, our study is currently in the data collection phase. Our analytical plan will determine the association between the number and type of school safety tactics and policies with the occurrence of intentional shootings and suspensions and expulsions in a national sample of approximately 650 K-12 public schools. Additional analyses will investigate the effect modification of specific covariates. Conclusion: As the first national, controlled study, its results will provide novel and needed data on the effectiveness of school safety tactics and policies in preventing intentional shootings at K-12 public schools. [ABSTRACT FROM AUTHOR]

Background: The liking for sweet taste is a powerful driver for consuming added sugars, and therefore, understanding how sweet liking is formed is a critical step in devising strategies to lower added sugars consumption. However, current research on the influence of genetic and environmental factors on sweet liking is mostly based on research conducted with individuals of European ancestry. Whether these results can be generalized to people of other ancestry groups warrants investigation. Methods: We will determine the differences in allele frequencies in sweet-related genetic variants and their effects on sweet liking in 426 adults of either African or East Asian ancestry, who have the highest and lowest average added sugars intake, respectively, among ancestry groups in the U.S. We will collect information on participants' sweet-liking phenotype, added sugars intake (sweetness exposure), anthropometric measures, place-of-birth, and for immigrants, duration of time living in the U.S. and age when immigrated. Ancestry-specific polygenic scores of sweet liking will be computed based on the effect sizes of the sweet-related genetic variants on the sweet-liking phenotype for each ancestry group. The predictive validity of the polygenic scores will be tested using individuals of African and East Asian ancestry from the UK Biobank. We will also compare sweet liking between U.S.-born individuals and immigrants within each ancestry group to test whether differences in environmental sweetness exposure during childhood affect sweet liking in adulthood. Discussion: Expanding genetic research on taste to individuals from ancestry groups traditionally underrepresented in such research is consistent with equity goals in sensory and nutrition science. Findings from this study will help in the development of a more personalized nutrition approach for diverse populations. Trial registration: This protocol has been preregistered with the Center for Open Science (https://doi.org/10.17605/OSF.IO/WPR9E). [ABSTRACT FROM AUTHOR]

BackgroundA high proportion of COVID-19 patients were reported to have cardiac involvements. Data pertaining to cardiac sequalae is of urgent importance to define subsequent cardiac surveillance.MethodsWe performed a systematic cardiac screening for 97 consecutive COVID-19 survivors including electrocardiogram (ECG), echocardiography, serum troponin and NT-proBNP assay 1-4 weeks after hospital discharge. Treadmill exercise test and cardiac magnetic resonance imaging (CMR) were performed according to initial screening results.ResultsThe mean age was 46.5 ± 18.6 years; 53.6% were men. All were classified with non-severe disease without overt cardiac manifestations and did not require intensive care. Median hospitalization stay was 17 days and median duration from discharge to screening was 11 days. Cardiac abnormalities were detected in 42.3% including sinus bradycardia (29.9%), newly detected T-wave abnormality (8.2%), elevated troponin level (6.2%), newly detected atrial fibrillation (1.0%), and newly detected left ventricular systolic dysfunction with elevated NT-proBNP level (1.0%). Significant sinus bradycardia with heart rate below 50 bpm was detected in 7.2% COVID-19 survivors, which appeared to be self-limiting and recovered over time. For COVID-19 survivors with persistent elevation of troponin level after discharge or newly detected T wave abnormality, echocardiography and CMR did not reveal any evidence of infarct, myocarditis, or left ventricular systolic dysfunction.ConclusionCardiac abnormality is common amongst COVID-survivors with mild disease, which is mostly self-limiting. Nonetheless, cardiac surveillance in form of ECG and/or serum biomarkers may be advisable to detect more severe cardiac involvement including atrial fibrillation and left ventricular dysfunction.

ImportanceKnowledge and attitude influence compliance and individuals' practices. The risk and protective factors associated with high compliance to these preventive measures are critical to enhancing pandemic preparedness.ObjectiveThis survey aims to assess differences in mental health, knowledge, attitudes, and practices (KAP) of preventive measures for COVID-19 amongst healthcare professionals (HCP) and non-healthcare professionals.DesignMulti-national cross-sectional study was carried out using electronic surveys between May-June 2020.SettingMulti-national survey was distributed across 36 countries through social media, word-of-mouth, and electronic mail.ParticipantsParticipants ≥21 years working in healthcare and non-healthcare related professions.Main outcomeRisk factors determining the difference in KAP towards personal hygiene and social distancing measures during COVID-19 amongst HCP and non-HCP.ResultsHCP were significantly more knowledgeable on personal hygiene (AdjOR 1.45, 95% CI -1.14 to 1.83) and social distancing (AdjOR 1.31, 95% CI -1.06 to 1.61) compared to non-HCP. They were more likely to have a positive attitude towards personal hygiene and 1.5 times more willing to participate in the contact tracing app. There was high compliance towards personal hygiene and social distancing measures amongst HCP. HCP with high compliance were 1.8 times more likely to flourish and more likely to have a high sense of emotional (AdjOR 1.94, 95% CI (1.44 to 2.61), social (AdjOR 2.07, 95% CI -1.55 to 2.78), and psychological (AdjOR 2.13, 95% CI (1.59-2.85) well-being.Conclusion and relevanceWhile healthcare professionals were more knowledgeable, had more positive attitudes, their higher sense of total well-being was seen to be more critical to enhance compliance. Therefore, focusing on the well-being of the general population would help to enhance their compliance towards the preventive measures for COVID-19.

BackgroundDuring COVID-19, the public actively sought non-pharmacological and self-management approaches to prevent infection. Little is known on the use of traditional, complementary and integrative medicine (TCIM) by the public as preventive measures. This study investigated the prevalence and patterns of TCIM use during the pandemic, and identified factors associated with its use among the general population in Hong Kong.MethodsAn online cross-sectional survey was conducted from November to December 2020. The survey solicited information on the respondents' sociodemographic characteristics, risk perception of the pandemic, and use of TCIM before and during the pandemic. Logistic regression analysis was conducted to determine predictors of TCIM use.ResultsIn total, 632 responses (completion rate = 88.1%) were analyzed. TCIM was used by 44.0% of respondents during the pandemic. The most popular forms of TCIM were vitamins or other dietary supplements (n = 160, 25.3%) and Chinese herbal medicine (n = 122, 19.3%) during the pandemic. The most frequently reported indication was strengthening the immune system, especially for vitamins or other dietary supplements (n = 142/160, 88.8%). Respondents who reported using TCIM were more likely to be female (adjusted odds ratio [aOR] = 1.82, 95% confidence interval [CI] = 1.29-2.59), had higher education attainment (aOR = 2.21, 95% CI = 1.39-3.59), and older-aged (age >55 years: aOR = 1.77, 95% CI = 1.04-3.02). Respondents who resided in districts with moderate to high number of confirmed COVID-19 cases (aOR = 1.60, 95% CI = 1.07-2.42) and had a higher level of risk perception (aOR = 1.04, 95% CI = 1.01-1.07) were also more likely to use TCIM.ConclusionTCIM was used commonly in Hong Kong during the COVID-19 pandemic. While vaccination and social distancing remain the mainstay of controlling the pandemic, professional bodies should proactively consider public preferences and provide information regarding the effectiveness and safety of TCIM for COVID-19 prevention and treatment.

Respiratory failure is a common condition faced by critically ill neonates with respiratory distress syndrome (RDS). High frequency oscillatory ventilation (HFOV) is often used for neonates with refractory respiratory failure related to RDS. Volume guarantee (VG) mode has been added to some HFOV ventilators for providing consistent tidal volume. We sought to examine the impact of adding the VG mode during HFOV on systemic and cerebral hemodynamics, which has not been studied to date. A neonatal piglet model of moderate to severe RDS was induced by saline lavage. Piglets (full term, age 1-3 days, weight 1.5-2.4 kg) were randomized to have RDS induced and receive either HFOV or HFOV+VG (n = 8/group) or sham-operation (n = 6) without RDS. Cardiac function measured by a Millar® catheter placed in the left ventricle as well as systemic and carotid hemodynamic and oxygen tissue saturation parameters were collected over 240 min of ventilation. Mean airway pressure, alveolar-arterial oxygen difference and left ventricular cardiac index of piglets on HFOV vs. HFOV+VG were not significantly different during the experimental period. Right common carotid artery flow index by in-situ ultrasonic flow measurement and cerebral tissue oxygen saturation (near-infrared spectroscopy) significantly decreased in HFOV+VG at 240 min compared to HFOV (14 vs. 31 ml/kg/min, and 30% vs. 43%, respectively; p