Interleukin-7 Availability Is Maintained by a Hematopoietic Cytokine Sink Comprising Innate Lymphoid Cells and T Cells.

Interleukin-7 (IL-7) availability determines the size and proliferative state of the resting T cell pool. However, the mechanisms that regulate steady-state IL-7 amounts are unclear. Using experimental lymphopenic mouse models and IL-7-induced homeostatic proliferation to measure IL-7 availability in vivo, we found that radioresistant cells were the source of IL-7 for both CD4+ and CD8+ T cells. Hematopoietic lineage cells, although irrelevant as a source of IL-7, were primarily responsible for limiting IL-7 availability via their expression of IL-7R. Unexpectedly, innate lymphoid cells were found to have a potent influence on IL-7 amounts in the primary and secondary lymphoid tissues. These results demonstrate that IL-7 homeostasis is achieved through consumption by multiple subsets of innate and adaptive immune cells.

Specimen collection is essential for modern science.

Natural history museums are vital repositories of specimens, samples and data that inform about the natural world; this Formal Comment revisits a Perspective that advocated for the adoption of compassionate collection practices, querying whether it will ever be possible to completely do away with whole animal specimen collection.

Estimating error rates for single molecule protein sequencing experiments.

The practical application of new single molecule protein sequencing (SMPS) technologies requires accurate estimates of their associated sequencing error rates. Here, we describe the development and application of two distinct parameter estimation methods for analyzing SMPS reads produced by fluorosequencing. A Hidden Markov Model (HMM) based approach, extends whatprot, where we previously used HMMs for SMPS peptide-read matching. This extension offers a principled approach for estimating key parameters for fluorosequencing experiments, including missed amino acid cleavages, dye loss, and peptide detachment. Specifically, we adapted the Baum-Welch algorithm, a standard technique to estimate transition probabilities for an HMM using expectation maximization, but modified here to estimate a small number of parameter values directly rather than estimating every transition probability independently. We demonstrate a high degree of accuracy on simulated data, but on experimental datasets, we observed that the model needed to be augmented with an additional error type, N-terminal blocking. This, in combination with data pre-processing, results in reasonable parameterizations of experimental datasets that agree with controlled experimental perturbations. A second independent implementation using a hybrid of DIRECT and Powell's method to reduce the root mean squared error (RMSE) between simulations and the real dataset was also developed. We compare these methods on both simulated and real data, finding that our Baum-Welch based approach outperforms DIRECT and Powell's method by most, but not all, criteria. Although some discrepancies between the results exist, we also find that both approaches provide similar error rate estimates from experimental single molecule fluorosequencing datasets.

Genitourinary cancer and family: The reverberating psychological and cardiovascular effects of a genitourinary cancer diagnosis on first-degree relatives and spouses.

BACKGROUND: The psychological and cardiovascular health impacts on family members of patients who have been diagnosed with cancer have not been well characterized. The purpose of this study is to determine whether a family member's cancer diagnosis influences the risk of psychological illness and cardiovascular disease in first-degree relatives and spouses of patients affected by cancer. METHODS: This retrospective cohort analysis evaluated the risk of psychological illness and cardiovascular disease in first-degree relatives and spouses of patients diagnosed with a genitourinary cancer between 1990 and 2015 compared to relatives of those not diagnosed with a genitourinary cancer. The Utah Population Database was used and familial linkage was determined. Follow-up included 1-, 3-, and 5-year intervals. Patients residing outside of Utah and first-degree relatives and spouses with psychological or cardiovascular disease diagnosed before a family member's cancer diagnosis were excluded. RESULTS: A total of 49,284 patients with a genitourinary cancer were identified with 77,938 first-degree relatives and spouses. A matched control group included 246,775 patients with 81,022 first-degree relatives and spouses. Via Cox proportional hazards models, a 10% increased risk of developing a psychological illness (hazard ratio [HR], 1.10; 95% CI, 1.00-1.20) and a 28% increased risk of developing cardiovascular disease (HR, 1.28; 95% CI, 1.17-1.41) at 1 year after a family member's cancer diagnosis were found. CONCLUSIONS: This study provides population-level evidence to support the hypothesis that cancer diagnoses will lead to adverse health outcomes for family members of patients with cancer. Increased clinical attention and support are needed to reduce the harm to families caused by cancer.

Ethnicity and outcomes for patients with gastrointestinal disorders attending an emergency department serving a multi-ethnic population.

BACKGROUND: Ethnic inequalities in acute health acute care are not well researched. We examined how attendee ethnicity influenced outcomes of emergency care in unselected patients presenting with a gastrointestinal (GI) disorder. METHODS: A descriptive, retrospective cohort analysis of anonymised patient level data for University Hospitals of Leicester emergency department attendees, from 1 January 2018 to 31 December 2021, receiving a diagnosis of a GI disorder was performed. The primary exposure of interest was self-reported ethnicity, and the two outcomes studied were admission to hospital and whether patients underwent clinical investigations. Confounding variables including sex and age, deprivation index and illness acuity were adjusted for in the analysis. Chi-squared and Kruskal-Wallis tests were used to examine ethnic differences across outcome measures and covariates. Multivariable logistic regression was used to examine associations between ethnicity and outcome measures. RESULTS: Of 34,337 individuals, median age 43 years, identified as attending the ED with a GI disorder, 68.6% were White. Minority ethnic patients were significantly younger than White patients. Multiple emergency department attendance rates were similar for all ethnicities (overall 18.3%). White patients had the highest median number of investigations (6, IQR 3-7), whereas those from mixed ethnic groups had the lowest (2, IQR 0-6). After adjustment for age, sex, year of attendance, index of multiple deprivation and illness acuity, all ethnic minority groups remained significantly less likely to be investigated for their presenting illness compared to White patients (Asian: aOR 0.80, 95% CI 0.74-0.87; Black: 0.67, 95% CI 0.58-0.79; mixed: 0.71, 95% CI 0.59-0.86; other: 0.79, 95% CI 0.67-0.93; p < 0.0001 for all). Similarly, after adjustment, minority ethnic attendees were also significantly less likely to be admitted to hospital (Asian: aOR 0.63, 95% CI 0.60-0.67; Black: 0.60, 95% CI 0.54-0.68; mixed: 0.60, 95% CI 0.51-0.71; other: 0.61, 95% CI 0.54-0.69; p < 0.0001 for all). CONCLUSIONS: Significant differences in usage patterns and disparities in acute care outcomes for patients of different ethnicities with GI disorders were observed in this study. These differences persisted after adjustment both for confounders and for measures of deprivation and illness acuity and indicate that minority ethnic individuals are less likely to be investigated or admitted to hospital than White patients.

Cardiovascular medication adherence testing in patients living with HIV: A single-centre observational study.

INTRODUCTION: People with HIV (PWH) are at an increased risk of developing cardiovascular disease (CVD) compared to HIV-negative individuals. We sought to evaluate the adherence to medications for CVD in PWH and identify factors associated with non-adherence to these medications. METHODS: We conducted a cross-sectional study at the University Hospitals of Leicester NHS Trust between 16 April 2019 and 8 November 2022. We recruited consecutive PWH, who were attending a routine follow-up outpatient appointment and were prescribed at least one medication for CVD. In addition, we included urinary adherence results of patients with samples collected as part of routine clinical care. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess if their prescribed medications (antihypertensives, diuretics, beta-blockers, lipid-lowering agents, antiplatelets, anticoagulants, antidiabetic medications) were present in the participant's urine sample. Multivariable models were used to identify demographic or clinical features that were associated with non-adherence. RESULTS: A total of 162 PWH were included in the analysis. Median age was 55 [interquartile range (IQR): 50-61] years, 63% were male, average time living with HIV was 15 years (IQR: 11-19) and the majority (98%) had an undetectable HIV viral load. In approximately one-third of patients (59/162), at least one prescribed medication of interest was not detected in urine. Non-adherence to lipid-lowering agents was common (35/88, 40%). On multivariable logistic regression, the number of prescribed cardiovascular medications, was associated with medication non-adherence [medication non-adherence, per one medication increase: adjusted odds ratio (95% confidence interval) = 1.78 (1.34-2.36); p < 0.001]. CONCLUSION: We found sub-optimal adherence to medications for CVD in PWH. In order to maximize the clinical benefit of statin therapy in PWH, factors requiring consideration include: improved medication adherence, awareness of polypharmacy, educational interventions and quantitative assessment of sub-optimal adherence through chemical adherence testing.

A multi-peak performance landscape for scale biting in an adaptive radiation of pupfishes.

The physical interactions between organisms and their environment ultimately shape diversification rates, but the contributions of biomechanics to evolutionary divergence are frequently overlooked. Here, we estimated a performance landscape for biting in an adaptive radiation of Cyprinodon pupfishes, including scale-biting and molluscivore specialists, and compared performance peaks with previous estimates of the fitness landscape in this system. We used high-speed video to film feeding strikes on gelatin cubes by scale eater, molluscivore, generalist and hybrid pupfishes and measured bite dimensions. We then measured five kinematic variables from 227 strikes using the SLEAP machine-learning model. We found a complex performance landscape with two distinct peaks best predicted gel-biting performance, corresponding to a significant non-linear interaction between peak gape and peak jaw protrusion. Only scale eaters and their hybrids were able to perform strikes within the highest performance peak, characterized by larger peak gapes and greater jaw protrusion. A performance valley separated this peak from a lower performance peak accessible to all species, characterized by smaller peak gapes and less jaw protrusion. However, most individuals exhibited substantial variation in strike kinematics and species could not be reliably distinguished by their strikes, indicating many-to-many mapping of morphology to performance. The two performance peaks observed in the lab were partially consistent with estimates of a two-peak fitness landscape measured in the wild, with the exception of the new performance peak for scale eaters. We thus reveal a new bimodal non-linear biomechanical model that connects morphology to performance to fitness in a sympatric radiation of trophic niche specialists.

Whole-genome sequencing of non-typeable Haemophilus influenzae isolated from a tertiary care hospital in Surabaya, Indonesia.

BACKGROUND: Haemophilus influenzae causes life-threatening invasive diseases such as septicaemia and meningitis. Reports on circulating H. influenzae causing invasive disease in lower-middle income settings, including Indonesia, are lacking. This study describes the serotype distributions and whole-genome sequence (WGS) data of H. influenzae isolated from hospitalized patients at Soetomo Hospital, Surabaya, Indonesia. METHODS: H. influenzae isolates were isolated from blood and pleural fluid specimens and identified using culture-based and molecular methods, followed by serotyping and WGS using RT‒PCR and Illumina MiSeq, respectively. Sequencing reads were assembled, and further analyses were undertaken to determine the genomic content and reconstruct the phylogeny. A second dataset consisting of publicly available H. influenzae genomes was curated to conduct phylogenetic analyses of isolates in this study in the context of globally circulating isolates. RESULTS: Ten H. influenzae isolates from hospitalized patients were collected, and septicaemia was the most common diagnosis (n=8). RT‒PCR and WGS were performed to determine whether all the isolates were nontypeable H. influenzae (NTHi). There were four newly identified STs distributed across the two main clusters. A total of 91 out of 126 virulence factor (VF)-related genes in Haemophilus sp. were detected in at least one isolate. Further evaluation incorporating a global collection of H. influenzae genomes confirmed the diverse population structure of NTHi in this study. CONCLUSION: This study showed that all H. influenzae recovered from invasive disease patients were nonvaccine-preventable NTHi isolates. The inclusion of WGS revealed four novel STs and the possession of key VF-associated genes.

A vertebrate adaptive radiation is assembled from an ancient and disjunct spatiotemporal landscape.

To investigate the origins and stages of vertebrate adaptive radiation, we reconstructed the spatial and temporal histories of adaptive alleles underlying major phenotypic axes of diversification from the genomes of 202 Caribbean pupfishes. On a single Bahamian island, ancient standing variation from disjunct geographic sources was reassembled into new combinations under strong directional selection for adaptation to the novel trophic niches of scale-eating and molluscivory. We found evidence for two longstanding hypotheses of adaptive radiation: hybrid swarm origins and temporal stages of adaptation. Using a combination of population genomics, transcriptomics, and genome-wide association mapping, we demonstrate that this microendemic adaptive radiation of novel trophic specialists on San Salvador Island, Bahamas experienced twice as much adaptive introgression as generalist populations on neighboring islands and that adaptive divergence occurred in stages. First, standing regulatory variation in genes associated with feeding behavior (prlh, cfap20, and rmi1) were swept to fixation by selection, then standing regulatory variation in genes associated with craniofacial and muscular development (itga5, ext1, cyp26b1, and galr2) and finally the only de novo nonsynonymous substitution in an osteogenic transcription factor and oncogene (twist1) swept to fixation most recently. Our results demonstrate how ancient alleles maintained in distinct environmental refugia can be assembled into new adaptive combinations and provide a framework for reconstructing the spatiotemporal landscape of adaptation and speciation.

Sleep deprivation and medication administration errors in registered nurses-A scoping review.

AIM: To explore whether sleep deprivation contributes to medication errors in registered nurses (RNs). BACKGROUND: Sleep deprivation is a potential issue for RNs, particularly those who work shifts. Sleep deprivation has been found to have a negative impact on numerous cognitive processes. Nurses administer several medications to patients a day, potentially while sleep deprived-anecdotal reports suggest that this could result in an increased risk of error occurring. DESIGN: A scoping review was conducted using the Prisma-ScR extension framework to explore what is known about the effect of RNs' sleep deprivation on medication administration errors. METHODS: A search of databases generated 171 results. When inclusion and exclusion criteria were applied, 18 empirical studies were analysed. Studies included retrospective analysis of errors, surveys of perceptions of causes and observational studies. RESULTS: Data indicated that RNs consider fatigue, which may be caused by sleep deprivation, to be a contributing factor to medication errors. The search only identified three observer studies, which provided conflicting results as to whether lack of sleep contributes to the error rate. Of the numerous tools used to measure sleep, the Pittsburgh Sleep Quality Index was the most frequently used. CONCLUSION: Although RNs anecdotally consider a lack of sleep potentially contributes to medication errors, there is insufficient research to provide robust evidence to confirm this assumption. NO PATIENT OR PUBLIC CONTRIBUTIONS: Patient or public contributions were not required for this scoping review. RELEVANCE TO CLINICAL PRACTICE: Sleep deprivation is a potential issue for nurses, especially those who work shifts. Poor sleep impacts cognitive processes that potentially could increase errors. Nurses should be aware of the impact sleep may have on patient safety.

Association between ethnicity and migration status with the prevalence of single and multiple long-term conditions in UK healthcare workers.

BACKGROUND: Healthcare workers' (HCW) well-being has a direct effect on patient care. However, little is known about the prevalence and patterns of long-term medical conditions in HCWs, especially those from ethnic minorities. This study evaluated the burden of multiple long-term conditions (MLTCs), i.e. the presence of two or more single long-term conditions (LTCs), among HCWs in the United Kingdom (UK) and variation by ethnicity and migration status. METHODS: We used baseline data from the UK-REACH cohort study collected December 2020-March 2021. We used multivariable logistic regression, adjusting for demographic, occupational and lifestyle factors to examine the relationship between self-reported LTCs/MLTCs and ethnicity, migration status and time since migration to the UK. RESULTS: Of 12,100 included HCWs, with a median age of 45 years (IQR: 34-54), 27% were overseas-born, and 30% were from non-White ethnic groups (19% Asian, 4% Black, 4% Mixed, 2% Other). The most common self-reported LTCs were anxiety (14.9%), asthma (12.2%), depression (10.7%), hypertension (8.7%) and diabetes (4.0%). Mental health conditions were more prevalent among UK-born than overseas-born HCWs for all ethnic groups (adjusted odds ratio (aOR) using White UK-born as the reference group each time: White overseas-born 0.77, 95%CI 0.66-0.95 for anxiety). Diabetes and hypertension were more common among Asian (e.g. Asian overseas, diabetes aOR 2.97, 95%CI 2.30-3.83) and Black (e.g. Black UK-born, hypertension aOR 1.77, 95%CI 1.05-2.99) groups than White UK-born. After adjustment for age, sex and deprivation, the odds of reporting MLTCs were lower in most ethnic minority groups and lowest for those born overseas, compared to White UK-born (e.g. White overseas-born, aOR 0.68, 95%CI 0.55-0.83; Asian overseas-born aOR 0.75, 95%CI 0.62-0.90; Black overseas-born aOR 0.52, 95%CI 0.36-0.74). The odds of MLTCs in overseas-born HCWs were equivalent to the UK-born population in those who had settled in the UK for ≥ 20 years (aOR 1.14, 95%CI 0.94-1.37). CONCLUSIONS: Among UK HCWs, the prevalence of common LTCs and odds of reporting MLTCs varied by ethnicity and migrant status. The lower odds of MLTCs in migrant HCWs reverted to the odds of MLTCs in UK-born HCWs over time. Further research on this population should include longitudinal studies with linkage to healthcare records. Interventions should be co-developed with HCWs from different ethnic and migrant groups focussed upon patterns of conditions prevalent in specific HCW subgroups to reduce the overall burden of LTCs/MLTCs.

Jaw size variation is associated with a novel craniofacial function for galanin receptor 2 in an adaptive radiation of pupfishes.

Understanding the genetic basis of novel adaptations in new species is a fundamental question in biology. Here we demonstrate a new role for galr2 in vertebrate craniofacial development using an adaptive radiation of trophic specialist pupfishes endemic to San Salvador Island, Bahamas. We confirmed the loss of a putative Sry transcription factor binding site upstream of galr2 in scale-eating pupfish and found significant spatial differences in galr2 expression among pupfish species in Meckel's cartilage using in situ hybridization chain reaction (HCR). We then experimentally demonstrated a novel role for Galr2 in craniofacial development by exposing embryos to Garl2-inhibiting drugs. Galr2-inhibition reduced Meckel's cartilage length and increased chondrocyte density in both trophic specialists but not in the generalist genetic background. We propose a mechanism for jaw elongation in scale-eaters based on the reduced expression of galr2 due to the loss of a putative Sry binding site. Fewer Galr2 receptors in the scale-eater Meckel's cartilage may result in their enlarged jaw lengths as adults by limiting opportunities for a circulating Galr2 agonist to bind to these receptors during development. Our findings illustrate the growing utility of linking candidate adaptive SNPs in non-model systems with highly divergent phenotypes to novel vertebrate gene functions.

Transmission of monkeypox/mpox virus: A narrative review of environmental, viral, host, and population factors in relation to the 2022 international outbreak.

Monkeypox virus (MPXV) has spread globally. Emerging studies have now provided evidence regarding MPXV transmission, that can inform rational evidence-based policies and reduce misinformation on this topic. We aimed to review the evidence on transmission of the virus. Real-world studies have isolated viable viruses from high-touch surfaces for as long as 15 days. Strong evidence suggests that the current circulating monkeypox (mpox) has evolved from previous outbreaks outside of Africa, but it is yet unknown whether these mutations may lead to an inherently increased infectivity of the virus. Strong evidence also suggests that the main route of current MPXV transmission is sexual; through either close contact or directly, with detection of culturable virus in saliva, nasopharynx, and sperm for prolonged periods and the presence of rashes mainly in genital areas. The milder clinical presentations and the potential presence of presymptomatic transmission in the current circulating variant compared to previous clades, as well as the dominance of spread amongst men who have sex with men (MSMs) suggests that mpox has a developed distinct clinical phenotype that has increased its transmissibility. Increased public awareness of MPXV transmission modalities may lead to earlier detection of the spillover of new cases into other groups.

Coverage, completion and outcomes of COVID-19 risk assessments in a multi-ethnic nationwide cohort of UK healthcare workers: a cross-sectional analysis from the UK-REACH Study.

INTRODUCTION: There are limited data on the outcomes of COVID-19 risk assessment in healthcare workers (HCWs) or the association of ethnicity, other sociodemographic and occupational factors with risk assessment outcomes. METHODS: We used questionnaire data from UK-REACH (UK Research study into Ethnicity And COVID-19 outcomes in Healthcare workers), an ethnically diverse, nationwide cohort of UK HCWs. We derived four binary outcomes: (1) offered a risk assessment; (2) completed a risk assessment; (3) working practices changed as a result of the risk assessment; (4) wanted changes to working practices after risk assessment but working practices did not change.We examined the association of ethnicity, other sociodemographic/occupational factors and actual/perceived COVID-19 risk variables on our outcomes using multivariable logistic regression. RESULTS: 8649 HCWs were included in total. HCWs from ethnic minority groups were more likely to report being offered a risk assessment than white HCWs, and those from Asian and black ethnic groups were more likely to report having completed an assessment if offered. Ethnic minority HCWs had lower odds of reporting having their work change as a result of risk assessment. Those from Asian and black ethnic groups were more likely to report no changes to their working practices despite wanting them.Previous SARS-CoV-2 infection was associated with lower odds of being offered a risk assessment and having adjustments made to working practices. DISCUSSION: We found differences in risk assessment outcomes by ethnicity, other sociodemographic/occupational factors and actual/perceived COVID-19 risk factors. These findings are concerning and warrant further research using actual (rather than reported) risk assessment outcomes in an unselected cohort.

Orangutans and the evolution of sharp stone tools.

Orangutans use stone tools in a variety of modes, including cutting. This behavior appears to be learned from trusted social partners.

Does A Hinged Operating Table Facilitate Sagittal Correction in Transforaminal Lumbar Interbody Fusion With Smith-Peterson Osteotomy? A Radiographic Analysis.

BACKGROUND: Osteotomies allow the restoration of appropriate sagittal alignment; however, closure of osteotomies can be challenging. Typical closure involves compressing pedicle screw heads across the rods, potentially causing screw loosening and failure. Motorized hinged operating tables are often used to assist with controlled closure of osteotomies without manual compression, but there is no published research quantifying the amount of correction provided solely by changes in the table angle. QUESTION/PURPOSE: What is the incremental amount of correction achieved by change in the table angle versus instrumented manipulation during osteotomy closure in transforaminal lumbar interbody fusion (TLIF) with Smith-Petersen osteotomy? METHODS: Sixty-one patients undergoing Smith-Peterson osteotomy and bilateral TLIF using a motorized hinged table from October 2019 to March 2022 were prospectively enrolled. Two patients did not undergo surgery, two did not have table extension, and seven did not have data collected intraoperatively because of disruptions in research protocols owing to the coronavirus-19 pandemic. Fifty patients (24 male, 26 female) who underwent a total of 73 osteotomies were included in the final analysis. The mean ± standard deviation age was 61 ±11 years, and the mean BMI was 31 ± 6 kg/m2. Patients were positioned prone on the table and flexed to 10° for decompression, Smith-Petersen osteotomy, and TLIF. The table was then extended in 5° increments, and radiographs were taken until 10° of extension was achieved or the osteotomy was fully closed. Changes in segmental lordosis across the operative site for each 5° increment were measured to the nearest degree by two reviewers. Intraclass correlation coefficients for segmental lordosis measurements at each table angle change were calculated as 0.97 to 0.98, with all p values < 0.001, indicating excellent agreement. RESULTS: Table change from 10° to 5° yielded a mean segmental lordosis change of 1.9° ± 1.5° (73 osteotomies), 5° to 0° yielded a change of 1.3° ± 0.9° (73 osteotomies), 0° to -5° yielded a change of 1.3° ± 1.0° (69 osteotomies), and -5° to -10° yielded a change of 1.1° ± 1.3° (61 osteotomies). Rod placement and compression yielded a mean 1.8° ± 2.0° of additional segmental lordosis. CONCLUSION: Using a motorized hinged table facilitated an average of 5.6° of total segmental lordosis correction during controlled Smith-Peterson osteotomy closure without the need for cantilevering forces across spinal instrumentation. Surgeons can use this technique to reduce the compression forces needed to close osteotomies, which could eliminate a potential source of complications.Level of Evidence Level II, therapeutic study.

Sacroiliac joint fusion navigation: how accurate is pin placement?

OBJECTIVE: Sacroiliac joint (SIJ) fusion utilizing intraoperative navigation requires a standard reference frame, which is often placed using a percutaneous pin. Proper placement ensures the correct positioning of SIJ fusion implants. There is currently no grading scheme for evaluation of pin placement into the pelvis. The purpose of this study was to evaluate the occurrence of ideal percutaneous pin placement into the posterior ilium during navigated SIJ fusion. METHODS: After IRB approval was obtained, electronic medical records and intraoperative computed tomography images of patients who underwent navigated SIJ fusion by the senior author between October 2013 and January 2020 were reviewed. A pin placement grading scheme and the definition of "ideal" placement were developed by the authors and deemed acceptable by fellow attending surgeons. Six attending surgeons completed two rounds of pin placement grading, and statistical analysis was conducted. RESULTS: Of 90 eligible patients, 73.3% had ideal pin placement, 17.8% medial/lateral breach, and 8.9% complete miss. Male patients were 3.7 times more likely to have ideal placement than females (p < 0.05). There was no relationship between BMI, SIJ fusion laterality, or pin placement laterality and ideal placement. Interobserver reliability was 0.72 and 0.70 in the first and second rounds, respectively, and defined as "substantial agreement." Intraobserver reliability ranged from 0.74 (substantial agreement) to 0.92 (almost perfect agreement). CONCLUSIONS: Nonideal pin placement occurred in 26.7% of cases, but a true "miss" into the sacrum was rare. Ideal pin placement was more likely in males and was not associated with BMI, SIJ fusion laterality, or pin placement laterality. The grading scheme developed has high intraobserver and interobserver reliability, indicating that it is reproducible and can be used for future studies. When placing percutaneous pins, surgeons must be aware of factors that can decrease placement accuracy, regardless of location.

Few Fixed Variants between Trophic Specialist Pupfish Species Reveal Candidate Cis-Regulatory Alleles Underlying Rapid Craniofacial Divergence.

Investigating closely related species that rapidly evolved divergent feeding morphology is a powerful approach to identify genetic variation underlying variation in complex traits. This can also lead to the discovery of novel candidate genes influencing natural and clinical variation in human craniofacial phenotypes. We combined whole-genome resequencing of 258 individuals with 50 transcriptomes to identify candidate cis-acting genetic variation underlying rapidly evolving craniofacial phenotypes within an adaptive radiation of Cyprinodon pupfishes. This radiation consists of a dietary generalist species and two derived trophic niche specialists-a molluscivore and a scale-eating species. Despite extensive morphological divergence, these species only diverged 10 kya and produce fertile hybrids in the laboratory. Out of 9.3 million genome-wide SNPs and 80,012 structural variants, we found very few alleles fixed between species-only 157 SNPs and 87 deletions. Comparing gene expression across 38 purebred F1 offspring sampled at three early developmental stages, we identified 17 fixed variants within 10 kb of 12 genes that were highly differentially expressed between species. By measuring allele-specific expression in F1 hybrids from multiple crosses, we found that the majority of expression divergence between species was explained by trans-regulatory mechanisms. We also found strong evidence for two cis-regulatory alleles affecting expression divergence of two genes with putative effects on skeletal development (dync2li1 and pycr3). These results suggest that SNPs and structural variants contribute to the evolution of novel traits and highlight the utility of the San Salvador Island pupfish system as an evolutionary model for craniofacial development.

Risk factors associated with SARS-CoV-2 infection in a multiethnic cohort of United Kingdom healthcare workers (UK-REACH): A cross-sectional analysis.

BACKGROUND: Healthcare workers (HCWs), particularly those from ethnic minority groups, have been shown to be at disproportionately higher risk of infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) compared to the general population. However, there is insufficient evidence on how demographic and occupational factors influence infection risk among ethnic minority HCWs. METHODS AND FINDINGS: We conducted a cross-sectional analysis using data from the baseline questionnaire of the United Kingdom Research study into Ethnicity and Coronavirus Disease 2019 (COVID-19) Outcomes in Healthcare workers (UK-REACH) cohort study, administered between December 2020 and March 2021. We used logistic regression to examine associations of demographic, household, and occupational risk factors with SARS-CoV-2 infection (defined by polymerase chain reaction (PCR), serology, or suspected COVID-19) in a diverse group of HCWs. The primary exposure of interest was self-reported ethnicity. Among 10,772 HCWs who worked during the first UK national lockdown in March 2020, the median age was 45 (interquartile range [IQR] 35 to 54), 75.1% were female and 29.6% were from ethnic minority groups. A total of 2,496 (23.2%) reported previous SARS-CoV-2 infection. The fully adjusted model contained the following dependent variables: demographic factors (age, sex, ethnicity, migration status, deprivation, religiosity), household factors (living with key workers, shared spaces in accommodation, number of people in household), health factors (presence/absence of diabetes or immunosuppression, smoking history, shielding status, SARS-CoV-2 vaccination status), the extent of social mixing outside of the household, and occupational factors (job role, the area in which a participant worked, use of public transport to work, exposure to confirmed suspected COVID-19 patients, personal protective equipment [PPE] access, aerosol generating procedure exposure, night shift pattern, and the UK region of workplace). After adjustment, demographic and household factors associated with increased odds of infection included younger age, living with other key workers, and higher religiosity. Important occupational risk factors associated with increased odds of infection included attending to a higher number of COVID-19 positive patients (aOR 2.59, 95% CI 2.11 to 3.18 for ≥21 patients per week versus none), working in a nursing or midwifery role (1.30, 1.11 to 1.53, compared to doctors), reporting a lack of access to PPE (1.29, 1.17 to 1.43), and working in an ambulance (2.00, 1.56 to 2.58) or hospital inpatient setting (1.55, 1.38 to 1.75). Those who worked in intensive care units were less likely to have been infected (0.76, 0.64 to 0.92) than those who did not. Black HCWs were more likely to have been infected than their White colleagues, an effect which attenuated after adjustment for other known risk factors. This study is limited by self-selection bias and the cross sectional nature of the study means we cannot infer the direction of causality. CONCLUSIONS: We identified key sociodemographic and occupational risk factors associated with SARS-CoV-2 infection among UK HCWs, and have determined factors that might contribute to a disproportionate odds of infection in HCWs from Black ethnic groups. These findings demonstrate the importance of social and occupational factors in driving ethnic disparities in COVID-19 outcomes, and should inform policies, including targeted vaccination strategies and risk assessments aimed at protecting HCWs in future waves of the COVID-19 pandemic. TRIAL REGISTRATION: The study was prospectively registered at ISRCTN (reference number: ISRCTN11811602).

Hesitancy for receiving regular SARS-CoV-2 vaccination in UK healthcare workers: a cross-sectional analysis from the UK-REACH study.

BACKGROUND: Regular vaccination against SARS-CoV-2 may be needed to maintain immunity in 'at-risk' populations, which include healthcare workers (HCWs). However, little is known about the proportion of HCWs who might be hesitant about receiving a hypothetical regular SARS-CoV-2 vaccination or the factors associated with this hesitancy. METHODS: Cross-sectional analysis of questionnaire data collected as part of UK-REACH, a nationwide, longitudinal cohort study of HCWs. The outcome measure was binary, either a participant indicated they would definitely accept regular SARS-CoV-2 vaccination if recommended or they indicated some degree of hesitancy regarding acceptance (probably accept or less likely). We used logistic regression to identify factors associated with hesitancy for receiving regular vaccination. RESULTS: A total of 5454 HCWs were included in the analysed cohort, 23.5% of whom were hesitant about regular SARS-CoV-2 vaccination. Black HCWs were more likely to be hesitant than White HCWs (aOR 2.60, 95%CI 1.80-3.72) as were those who reported a previous episode of COVID-19 (1.33, 1.13-1.57 [vs those who tested negative]). Those who received influenza vaccination in the previous two seasons were over five times less likely to report hesitancy for regular SARS-CoV-2 vaccination than those not vaccinated against influenza in either season (0.18, 0.14-0.21). HCWs who trusted official sources of vaccine information (such as NHS or government adverts or websites) were less likely to report hesitancy for a regular vaccination programme. Those who had been exposed to information advocating against vaccination from friends and family were more likely to be hesitant. CONCLUSIONS: In this study, nearly a quarter of UK HCWs were hesitant about receiving a regular SARS-CoV-2 vaccination. We have identified key factors associated with hesitancy for regular SARS-CoV-2 vaccination, which can be used to identify groups of HCWs at the highest risk of vaccine hesitancy and tailor interventions accordingly. Family and friends of HCWs may influence decisions about regular vaccination. This implies that working with HCWs and their social networks to allay concerns about SARS-CoV-2 vaccination could improve uptake in a regular vaccination programme. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN11811602.