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BACKGROUND: Previous studies have focused on the development and evaluation of care bundles to reduce the risk of surgical site infection (SSI) throughout the perioperative period. A focused examination of the technical/surgical aspects of SSI reduction during CRS has not been conducted. This study aimed to develop an expert consensus on intraoperative technical/surgical aspects of SSI prevention by the surgical team during colorectal surgery (CRS). STUDY DESIGN: In a modified Delphi process, a panel of 15 colorectal surgeons developed a consensus on intraoperative technical/surgical aspects of SSI prevention undertaken by surgical personnel during CRS using information from a targeted literature review and expert opinion. Consensus was developed with up to three rounds per topic, with a prespecified threshold of ≥70% agreement. RESULTS: In 3 Delphi rounds, the 15 panelists achieved consensus on 16 evidence-based statements. The consensus panel supported the use of wound protectors/retractors, sterile incision closure tray, preclosure glove change, and antimicrobial sutures in reducing SSI along with wound irrigation with aqueous iodine and closed-incision negative pressure wound therapy in high-risk, contaminated wounds. CONCLUSIONS: Using a modified Delphi method, consensus has been achieved on a tailored set of recommendations on technical/surgical aspects that should be considered by surgical personnel during CRS to reduce the risk of SSI, particularly in areas where the evidence base is controversial or lacking. This document forms the basis for ongoing evidence for the topics discussed in this article or new topics based on newly emerging technologies in CRS.

Autoimmune hepatitis (AIH) is a poorly understood, chronic disease, for which corticosteroids are still the mainstay of therapy and most patients undergo liver biopsy to obtain a diagnosis. We aimed to determine if there was a transcriptomic signature of AIH in the peripheral blood and investigate underlying biologic pathways revealed by gene expression analysis. Whole blood RNA from 75 AIH patients and 25 healthy volunteers was extracted and sequenced. Differential gene expression analysis revealed 249 genes that were significantly differentially expressed in AIH patients compared to controls. Using a random forest algorithm, we determined that less than 10 genes were sufficient to differentiate the two groups in our cohort. Interferon signaling was more active in AIH samples compared to controls, regardless of treatment status. Pegivirus sequences were detected in five AIH samples and 1 healthy sample. The gene expression data and clinical metadata were used to determine 12 genes that were significantly associated with advanced fibrosis in AIH. AIH patients with a partial response to therapy demonstrated decreased evidence of a CD8+ T cell gene expression signal. These findings represent progress in understanding a disease in need of better tests, therapies, and biomarkers.

Hybrid incompatibilities occur when interactions between opposite ancestry alleles at different loci reduce the fitness of hybrids. Most work on incompatibilities has focused on those that are "intrinsic," meaning they affect viability and sterility in the laboratory. Theory predicts that ecological selection can also underlie hybrid incompatibilities, but tests of this hypothesis using sequence data are scarce. In this article, we compiled genetic data for F2 hybrid crosses between divergent populations of threespine stickleback fish (Gasterosteus aculeatus L.) that were born and raised in either the field (seminatural experimental ponds) or the laboratory (aquaria). Because selection against incompatibilities results in elevated ancestry heterozygosity, we tested the prediction that ancestry heterozygosity will be higher in pond-raised fish compared to those raised in aquaria. We found that ancestry heterozygosity was elevated by approximately 3% in crosses raised in ponds compared to those raised in aquaria. Additional analyses support a phenotypic basis for incompatibility and suggest that environment-specific single-locus heterozygote advantage is not the cause of selection on ancestry heterozygosity. Our study provides evidence that, in stickleback, a coarse-albeit indirect-signal of environment-dependent hybrid incompatibility is reliably detectable and suggests that extrinsic incompatibilities can evolve before intrinsic incompatibilities.

Cancers arising from germline DNA mismatch repair deficiency or polymerase proofreading deficiency (MMRD and PPD) in children harbour the highest mutational and microsatellite insertion-deletion (MS-indel) burden in humans. MMRD and PPD cancers are commonly lethal due to the inherent resistance to chemo-irradiation. Although immune checkpoint inhibitors (ICIs) have failed to benefit children in previous studies, we hypothesized that hypermutation caused by MMRD and PPD will improve outcomes following ICI treatment in these patients. Using an international consortium registry study, we report on the ICI treatment of 45 progressive or recurrent tumors from 38 patients. Durable objective responses were observed in most patients, culminating in a 3 year survival of 41.4%. High mutation burden predicted response for ultra-hypermutant cancers (>100 mutations per Mb) enriched for combined MMRD + PPD, while MS-indels predicted response in MMRD tumors with lower mutation burden (10-100 mutations per Mb). Furthermore, both mechanisms were associated with increased immune infiltration even in 'immunologically cold' tumors such as gliomas, contributing to the favorable response. Pseudo-progression (flare) was common and was associated with immune activation in the tumor microenvironment and systemically. Furthermore, patients with flare who continued ICI treatment achieved durable responses. This study demonstrates improved survival for patients with tumors not previously known to respond to ICI treatment, including central nervous system and synchronous cancers, and identifies the dual roles of mutation burden and MS-indels in predicting sustained response to immunotherapy.

Innate lymphoid cells (ILC) promote lung inflammation in asthma through cytokine production. RNA-binding proteins (RBPs) are critical post-transcriptional regulators, although less is known about RBPs in ILC biology. Here, we demonstrate that RNA-binding motif 3 (RBM3) is highly expressed in lung ILCs and is further induced by alarmins TSLP and IL-33. Rbm3-/- and Rbm3-/-Rag2-/- mice exposed to asthma-associated Alternaria allergen develop enhanced eosinophilic lung inflammation and ILC activation. IL-33 stimulation studies in vivo and in vitro show that RBM3 suppressed lung ILC responses. Further, Rbm3-/- ILCs from bone marrow chimeric mice display increased ILC cytokine production suggesting an ILC-intrinsic suppressive function of RBM3. RNA-sequencing of Rbm3-/- lung ILCs demonstrates increased expression of type 2/17 cytokines and cysteinyl leukotriene 1 receptor (CysLT1R). Finally, Rbm3-/-Cyslt1r-/- mice show dependence on CysLT1R for accumulation of ST2+IL-17+ ILCs. Thus, RBM3 intrinsically regulates lung ILCs during allergen-induced type 2 inflammation that is partially dependent on CysLT1R.

β-adrenoceptor (β-AR) agonists are known to antagonize thrombin-induced impairment (TII) of bovine and ovine lung endothelial barrier function. The effects of adrenoceptor agonists and other vasoactive agents on human lung microvascular endothelial cell (HULEC-5a) barrier function upon thrombin exposure have not been studied. Furthermore, it is unknown whether the in vitro effects of adrenoceptor agonists translate to lung protective effects in vivo. We observed that epinephrine, norepinephrine, and phenylephrine enhanced normal and prevented TII of HULEC-5a barrier function. Arginine vasopressin and angiotensin II were ineffective. α1B-, α2A/B-, and β1/2-ARs were detectable in HULEC-5a by RT-PCR. Propranolol but not doxazosin blocked the effects of all adrenoceptor agonists. Phenylephrine stimulated β2-AR-mediated Gαs activation with 13-fold lower potency than epinephrine. The EC50 to inhibit TII of HULEC-5a barrier function was 1.8 ± 1.9 nM for epinephrine and >100 nM for phenylephrine. After hemorrhagic shock and fluid resuscitation in rats, Evans blue extravasation into the lung increased threefold (p < 0.01 vs. sham). Single low-dose (1.8 μg/kg) epinephrine administration at the beginning of resuscitation had no effects on blood pressure and reduced Evans blue extravasation by 60% (p < 0.05 vs. vehicle). Our findings confirm the effects of β-adrenoceptor agonists in HULEC-5a and suggest that low-dose β-adrenoceptor agonist treatment protects lung vascular barrier function after traumatic hemorrhagic shock.

The Arctic and boreal regions are experiencing a rapid increase in temperature, resulting in a changing cryosphere, increasing human activity, and potentially increasing high-latitude methane emissions. Satellite observations from Sentinel-5P TROPOMI provide an unprecedented coverage of a column-averaged dry-air mole fraction of methane (XCH4) in the Arctic, compared to previous missions or in situ measurements. The purpose of this study is to support and enhance the data used for high-latitude research through presenting a systematic evaluation of TROPOMI methane products derived from two different processing algorithms: the operational product (OPER) and the scientific product (WFMD), including the comparison of recent version changes of the products (OPER, OPER rpro, WFMD v1.2, and WFMD v1.8). One finding is that OPER rpro yields lower XCH4 than WFMD v1.8, the difference increasing towards the highest latitudes. TROPOMI product differences were evaluated with respect to ground-based high-latitude references, including four Fourier Transform Spectrometer in the Total Carbon Column Observing Network (TCCON) and five EM27/SUN instruments in the Collaborative Carbon Column Observing Network (COCCON). The mean TROPOMI–TCCON GGG2020 daily median XCH4 difference was site-dependent and varied for OPER rpro from −0.47 ppb to 22.4 ppb, and for WFMD v1.8 from 1.2 ppb to 19.4 ppb with standard deviations between 13.0 and 20.4 ppb and 12.5–15.0 ppb, respectively. The TROPOMI–COCCON daily median XCH4 difference varied from −26.5 ppb to 5.6 ppb for OPER rpro, with a standard deviation of 14.0–28.7 ppb, and from −5.0 ppb to 17.2 ppb for WFMD v1.8, with a standard deviation of 11.5–13.0 ppb. Although the accuracy and precision of both TROPOMI products are, on average, good compared to the TCCON and COCCON, a persistent seasonal bias in TROPOMI XCH4 (high values in spring; low values in autumn) is found for OPER rpro and is reflected in the higher standard deviation values. A systematic decrease of about 7 ppb was found between TCCON GGG2014 and GGG2020 product update highlighting the importance of also ensuring the reliability of ground-based retrievals. Comparisons to atmospheric profile measurements with AirCore carried out in Sodankylä, Northern Finland, resulted in XCH4 differences comparable to or smaller than those from ground-based remote sensing.

For electric vehicle (EV) charging in North America, three AC connectors are standardized, resulting in a proliferation of charging stations which can only charge one of the three types of EV. We propose a “Universal EV Outlet” that works with an EV “carry along” charging cable—one end of the cable has a connector specific to that user’s EV, the other a plug for the Universal EV Outlet. This proposal does not interfere with, nor require change to, any existing charging stations. It does not require any new types of inlets on EVs. The components are already standardized. Eight use cases are examined to illustrate the advantages, and some limitations, of the Universal EV Outlet. The use cases illustrate how this solution: resolves the problem of multiple AC charging connectors, makes today’s “EV Ready” building codes more adaptable, lowers capital and maintenance costs, creates a solution to curbside and urban charging, increases energy efficiency, enables higher power three-phase AC charging for heavy vehicles, and facilitates use of EVs for building backup power and for vehicle-to-grid. Finally, we propose a standards-based active cable used with the Universal EV Outlet, which would allow fast and secure EV identification for curbside or other shared charging locations, usable today without modifications to current EVs.

Black-White disparities in gifted enrollment persist across U.S. school systems. In this study, we examined whether these disparities depend on county-level rates of anti-Black bias. We drew data from the Civil Rights Data Collection, the Education Opportunity Project, and the Race Implicit Association Database. Based on a series of heteroskedastic fractional probit regression models, we found that county-level rates of anti-Black bias predict Black-White disparities in gifted and talented enrollment, with gaps being largest in counties with elevated rates of anti-Black bias and virtually non-existent in counties with low levels of anti-Black bias. These findings persist after accounting for achievement and other observable differences across counties, unobserved variation in state-level gifted and talented policies and are consistent for county-level estimates of both explicit and implicit measures of anti-Black bias.

Background: In the United States, approximately seven million students are chronically absent from school each year. Students with disabilities are more likely to be chronically absent than students without a disability. Using the bioecological systems theory, this study examined the impact of individual developmental disabilities and disability severity on frequent school absenteeism. Methods: This study conducted a secondary analysis using combined data from the National Survey of Children's Health, 2016 to 2017. Bivariate relationships were examined using x2 tests, and odds ratios adjusting for individual, microsystem, and macrosystem factors were calculated using multivariable logistic regressions. Results: Children with selected developmental disabilities had significantly higher odds of absenteeism compared to children without developmental disabilities. The odds of absenteeism differed between age ranges and developmental disability conditions. A dose-response relationship was also present for certain developmental disabilities in that children with a moderate to severe condition had higher odds of absenteeism. Conclusions: Children with one or more developmental disabilities had higher odds of absenteeism compared to children with typical development. However, odds were not consistent across age, condition, or condition severity. This population may benefit from tailored school interventions to promote regular attendance and mitigate the impact of frequent school absenteeism on education.

Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials cost-effectiveness analyses and key areas for future research.

Scientific communication is facilitated by a data-driven, scientifically sound taxonomy that considers the end-user's needs and established successful practice. In 2013, the Fusarium community voiced near unanimous support for a concept of Fusarium that represented a clade comprising all agriculturally and clinically important Fusarium species, including the F. solani species complex (FSSC). Subsequently, this concept was challenged in 2015 by one research group who proposed dividing the genus Fusarium into seven genera, including the FSSC described as members of the genus Neocosmospora, with subsequent justification in 2018 based on claims that the 2013 concept of Fusarium is polyphyletic. Here, we test this claim and provide a phylogeny based on exonic nucleotide sequences of 19 orthologous protein-coding genes that strongly support the monophyly of Fusarium including the FSSC. We reassert the practical and scientific argument in support of a genus Fusarium that includes the FSSC and several other basal lineages, consistent with the longstanding use of this name among plant pathologists, medical mycologists, quarantine officials, regulatory agencies, students, and researchers with a stake in its taxonomy. In recognition of this monophyly, 40 species described as genus Neocosmospora were recombined in genus Fusarium, and nine others were renamed Fusarium. Here the global Fusarium community voices strong support for the inclusion of the FSSC in Fusarium, as it remains the best scientific, nomenclatural, and practical taxonomic option available.

PurposeConstitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals.Patients and methodsData were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation.ResultsA total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically (P < .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively (P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance (P < .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years.ConclusionSurveillance and early cancer detection are associated with improved OS for individuals with CMMRD.

This article shares development of a mentor teacher training program to support teacher candidates in their student teaching internship. The mentor teacher training program includes three parts: (a) online training on internship processes and procedures, co-teaching, and a department developed Framework for Extended Oral and Written Feedback, (b) face-to-face orientation session to clarify co-teaching and feedback framework, and (c) co-observation of intern candidates by faculty supervisor and mentor teacher. The goal of the mentor teacher training program is to orient mentor teachers to the internship and to train them in providing high quality, actionable feedback that leads the teacher candidate to improved practice.

Abstract Background The Connemara pony (CP) is an Irish breed that has experienced varied selection by breeders over the last fifty years, with objectives ranging from the traditional hardy pony to an agile athlete. We compared these ponies with well-studied Warmblood (WB) horses, which are also selectively bred for athletic performance but with a much larger census population. Using genome-wide single nucleotide polymorphism (SNP) and whole-genome sequencing data from 116 WB (94 UK WB and 22 European WB) and 36 CP (33 UK CP and 3 US CP), we studied the genomic diversity, inbreeding and population structure of these breeds. Results The k-means clustering approach divided both the CP and WB populations into four genetic groups, among which the CP genetic group 1 (C1) associated with non-registered CP, C4 with US CP, WB genetic group 1 (W1) with Holsteiners, and W3 with Anglo European and British WB. Maximum and mean linkage disequilibrium (LD) varied significantly between the two breeds (mean from 0.077 to 0.130 for CP and from 0.016 to 0.370 for WB), but the rate of LD decay was generally slower in CP than WB. The LD block size distribution peaked at 225 kb for all genetic groups, with most of the LD blocks not exceeding 1 Mb. The top 0.5% harmonic mean pairwise fixation index (FST) values identified ontology terms related to cancer risk when the four CP genetic groups were compared. The four CP genetic groups were less inbred than the WB genetic groups, but C2, C3 and C4 had a lower proportion of shorter runs of homozygosity (ROH) (74 to 76%

Background: Over 48,000 people died by firearm in the United States in 2021. Firearm violence has many inciting factors, but the full breadth of associations has not been characterized. We explored several state-level factors including factors not previously studied or insufficiently studied, to determine their association with state firearm-related death rates. Methods: Several state-level factors, including firearm open carry (OC) and concealed carry (CC) laws, state rank, partisan lean, urbanization, poverty rate, anger index, and proportion of college-educated adults, were assessed for association with total firearm-related death rates (TFDR). Secondary outcomes were firearm homicide (FHR) and firearm suicide rates (FSR). Exploratory data analysis with correlation plots and ANOVA was performed. Univariable and multivariable linear regression on the rate of firearm-related deaths was also performed. Results: All 50 states were included. TFDR and FSR were higher in permitless OC and permitless CC states. FHR did not differ based on OC or CC category. Open carry and CC were eliminated in all three regression models due to a lack of significance. Significant factors for each model were: 1) TFDR – partisan lean, urbanization, poverty rate, and state ranking; 2) FHR – poverty rate; 3) FSR – partisan lean and urbanization. Conclusions: Neither open nor concealed carry is associated with firearm-related death rates when socioeconomic factors are concurrently considered. Factors associated with firearm homicide and suicide differ and will likely require separate interventions to reduce firearm-related deaths. Key message: Neither open carry nor concealed carry law are associated with total firearm-related death rate, but poverty rate, urbanization, partisan lean, and state ranking are associated. When analyzing firearm homicide and suicide rates separately, poverty rate is strongly associated with firearm homicide rate, while urbanization and partisan lean are associated with firearm suicide rate.

Abstract Sleep is responsible for maintenance and regulatory functions in human physiology. Insufficient sleep has been associated with cardiovascular disease, weight gain, obesity, inflammation, and morbidity. University students are at high risk under normal circumstances of stress and anxiety due to extracurricular demands, competing pressures on student time, long study hours, and financial concerns. The COVID 19 pandemic has disrupted normal college students’ lives adding stresses such as lost jobs and family responsibilities such as serving as caregivers, which disproportionally affect minority and rural student. This study aimed to assess the correlation of sleep disorders in New Mexico State University students during COVID 19 with selected variates including base demographics (e.g., gender, age, etc.), lifestyle metrics (e.g., employment status, discipline, class, etc.), living arrangements (e.g., housing type, number of children, etc.), alcohol and tobacco use, vaccination status, family COVID status, and family vaccination status. Single- and multi-factor logistic regressions were performed to analyze the data on the students. Qualtrics software was used to collect data on demographics and sleep disorders. R software was used for data analysis. Correlations were found between sleeping less, sleeping more, and disturbed sleep among several covariate categories. For all three responses, being married (sleeping less: OR = 0.342, 95% CI = 0.181–0.642, sleeping more: OR = 0.265, 95% CI = 0.111–0.591; disturbed sleeping: OR = 0.345, 95% CI = 0.182–0.650), frequency of feeling sleepy-very often (OR = 16.87, 95% CI = 6.571–47.434; OR = 8.393, 95% CI = 3.086–25.298; OR = 13.611, 95% CI = 5.409–36.975) and change in diet- quality decreased (OR = 7.304, 95% CI = 3.615–15.270; OR = 5.250, 95% CI = 2.309–12.558; OR = 4.181, 95% CI = 2.145–8.359) were all significant correlated to change in sleeping behavior. Other correlations were found among covariates and sleep changes. Several covariates were determined to be correlated with the effect of COVID-19 on sleeping.

Abstract Background Randomized controlled trials (RCTs) are a critical component of evidence-based medicine and the evolution of patient care. However, the costs of conducting a RCT can be prohibitive. A promising approach toward reduction of costs and lessening of the burden of intensive and lengthy patient follow-up is the use of routinely collected healthcare data (RCHD), commonly called real-world data. We propose a scoping review to identify existing RCHD case definitions of breast cancer progression and survival and their diagnostic performance. Methods We will search MEDLINE, EMBASE, and CINAHL to identify primary studies of women with either early-stage or metastatic breast cancer, managed with established therapies, that evaluated the diagnostic accuracy of one or more RCHD-based case definitions or algorithms of disease progression (i.e., recurrence, progression-free survival, disease-free survival, or invasive disease-free survival) or survival (i.e., breast-cancer-free survival or overall survival) compared with a reference standard measure (e.g., chart review or a clinical trial dataset). Study characteristics and descriptions of algorithms will be extracted along with measures of the diagnostic accuracy of each algorithm (e.g., sensitivity, specificity, positive predictive value, negative predictive value), which will be summarized both descriptively and in structured figures/tables. Discussion Findings from this scoping review will be clinically meaningful for breast cancer researchers globally. Identification of feasible and accurate strategies to measure patient-important outcomes will potentially reduce RCT budgets as well as lessen the burden of intensive trial follow-up on patients. Systematic review registration Open Science Framework ( https://doi.org/10.17605/OSF.IO/6D9RS )

Abstract Background As a COVID-19 risk mitigation measure, Australia closed its international borders for two years with significant socioeconomic disruption including impacting approximately 30% of the Australian population who are migrants. Migrant populations during the peripartum often rely on overseas relatives visiting for social support. High quality social support is known to lead to improved health outcomes with disruption to support a recognised health risk. Aim To explore women’s experience of peripartum social support during the COVID-19 pandemic in a high migrant population. To quantify type and frequency of support to identify characteristics of vulnerable perinatal populations for future pandemic preparedness. Methods A mixed methods study with semi-structured interviews and a quantitative survey was conducted from October 2020 to April 2021. A thematic approach was used for analysis. Results There were 24 participants interviewed both antenatally and postnatally (22 antenatal; 18 postnatal). Fourteen women were migrants and 10 Australian born. Main themes included; ‘Significant disruption and loss of peripartum support during the COVID-19 pandemic and ongoing impact for migrant women’; ‘Husbands/partners filling the support gap’ and ‘Holding on by a virtual thread’. Half of the participants felt unsupported antenatally. For Australian born women, this dissipated postnatally, but migrants continued to feel unsupported. Migrant women discussed partners stepped into traditional roles and duties of absent mothers and mothers-in-law who were only available virtually. Conclusion This study identified disrupted social support for migrant women during the pandemic, providing further evidence that the pandemic has disproportionately impacted migrant populations. However, the benefits identified in this study included high use of virtual support, which could be leveraged for improving clinical care in the present and in future pandemics. The COVID-19 pandemic impacted most women’s peripartum social support with migrant families having ongoing disruption. Gains in the pandemic included greater gender equity for domestic work as husbands/partners increased their contribution to domestic work and childcare.

Abstract Background Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections play a key role in treating a range of macular diseases. The effectiveness of these therapies is dependent on patients’ adherence (the extent to which a patient takes their medicines as per agreed recommendations from the healthcare provider) and persistence (continuation of the treatment for the prescribed duration) to their prescribed treatment regimens. The aim of this systematic review was to demonstrate the need for further investigation into the prevalence of, and factors contributing to, patient-led non-adherence and non-persistence, thus facilitating improved clinical outcomes. Methods Systematic searches were conducted in Google Scholar, Web of Science, PubMed, MEDLINE, and the Cochrane Library. Studies in English conducted before February 2023 that reported the level of, and/or barriers to, non-adherence or non-persistence to intravitreal anti-VEGF ocular disease therapy were included. Duplicate papers, literature reviews, expert opinion articles, case studies, and case series were excluded following screening by two independent authors. Results Data from a total of 409,215 patients across 52 studies were analysed. Treatment regimens included pro re nata, monthly and treat-and-extend protocols; study durations ranged from 4 months to 8 years. Of the 52 studies, 22 included a breakdown of reasons for patient non-adherence/non-persistence. Patient-led non-adherence varied between 17.5 and 35.0% depending on the definition used. Overall pooled prevalence of patient-led treatment non-persistence was 30.0% (P = 0.000). Reasons for non-adherence/non-persistence included dissatisfaction with treatment results (29.9%), financial burden (19%), older age/comorbidities (15.5%), difficulty booking appointments (8.5%), travel distance/social isolation (7.9%), lack of time (5.8%), satisfaction with the perceived improvement in their condition (4.4%), fear of injection (4.0%), loss of motivation (4.0%), apathy towards eyesight (2.5%), dissatisfaction with facilities 2.3%, and discomfort/pain (0.3%). Three studies found non-adherence rates between 51.6 and 68.8% during the COVID-19 pandemic, in part due to fear of exposure to COVID-19 and difficulties travelling during lockdown. Discussion Results suggest high levels of patient-led non-adherence/non-persistence to anti-VEGF therapy, mostly due to dissatisfaction with treatment results, a combination of comorbidities, loss of motivation and the burden of travel. This study provides key information on prevalence and factors contributing to non-adherence/non-persistence in anti-VEGF treatment for macular diseases, aiding identification of at-risk individuals to improve real-world visual outcomes. Improvements in the literature can be achieved by establishing uniform definitions and standard timescales for what constitutes non-adherence/non-persistence. Systematic review registration PROSPERO CRD42020216205.

Abstract Improving cattle feed efficiency through selection of residual feed intake (RFI) is a widely accepted approach to sustainable beef production. A greater understanding of the molecular control of RFI in various breeds offered contrasting diets is necessary for the accurate identification of feed efficient animals and will underpin accelerated genetic improvement of the trait. The aim of this study was to determine genes and biological processes contributing to RFI across varying breed type and dietary sources in skeletal muscle tissue. Residual feed intake was calculated in Charolais and Holstein–Friesian steers across multiple dietary phases (phase-1: high concentrate (growing-phase); phase-2: zero-grazed grass (growing-phase); phase-3: high concentrate (finishing-phase). Steers divergent for RFI within each breed and dietary phase were selected for muscle biopsy collection, and muscle samples subsequently subjected to RNAseq analysis. No gene was consistently differentially expressed across the breed and diet types examined. However, pathway analysis revealed commonality across breeds and diets for biological processes including fatty acid metabolism, immune function, energy production and muscle growth. Overall, the lack of commonality of individual genes towards variation in RFI both within the current study and compared to the published literature, suggests other genomic features warrant further evaluation in relation to RFI.

Abstract Background The purpose of this study was to investigate associations between self‐reported distress (anxiety/depression) and satisfaction with and desire for virtual follow‐up (VFU) care among cancer patients during and beyond the COVID‐19 pandemic. Methods Breast and prostate cancer patients receiving VFU at an urban cancer centre in Toronto, Canada completed an online survey on their sociodemographic, clinical, and technology, characteristics and experience with and views on VFU. EQ5D‐5 L was used to assess distress. Statistical models adjusted for age, gender, education, income and Internet confidence. Results Of 352 participants, average age was 65 years, 48% were women,79% were within 5 years of treatment completion, 84% had college/university education and 74% were confident Internet users. Nearly, all (98%) had a virtual visit via phone and 22% had a virtual visit via video. The majority of patients (86%) were satisfied with VFU and 70% agreed that they would like VFU options after the COVID‐19 pandemic. Participants who reported distress and who were not confident using the Internet for health purposes were significantly less likely to be satisfied with VFU (OR = 0.4; 95% CI: 0.2–0.8 and OR = 0.19; 95% CI: 0.09–0.38, respectively) and were less likely to desire VFU option after the COVID‐19 pandemic (OR = 0.49; 95% CI: 0.30–0.82 and OR = 0.41; 95% CI: 0.23–0.70, respectively). Conclusions The majority of respondents were satisfied with VFU and would like VFU options after the COVID‐19 pandemic. Future research should determine how to optimize VFU options for cancer patients who are distressed and who are less confident using virtual care technology.

Introduction: Individuals living with sickle cell disease experience high levels of morbidity that result in frequent utilization of the emergency department. The objective of this study was to provide updated national estimates of emergency department utilization associated with sickle cell disease in the U.S. Methods: Data from the National Hospital Ambulatory Medical Care Survey for the years 1999–2020 were analyzed. Complex survey analysis was utilized to produce national estimates overall and by patient age groups. Results: On average, approximately 222,612 emergency department visits occurred annually among individuals with sickle cell disease, a nearly 13% increase from prior estimates. The annual volume of emergency department visits steadily increased over time, and pain remains the most common patient-cited reason for visiting the emergency department. Patient-reported pain levels for individuals with sickle cell disease were high, with 64% of visits associated with severe pain and 21% associated with moderate pain. Public insurance sources continue to cover most visits, with Medicaid paying for 60% of visits and Medicare paying for 12% of visits. The average time spent in the emergency department increased from previous estimates by about an hour, rising to approximately 6 hours. The average wait time to see a provider was 53 minutes. Conclusions: Utilization of the emergency department by individuals living with sickle cell disease remains high, especially for pain. With more than half of patients with sickle cell disease reporting severe pain levels, emergency department staff should be prepared to assess and treat sickle cell disease–related pain following evidence-based guidelines and recommendations. The findings of this study can help improve care in this population.

Caregiver-assisted testing using HIV self-test (CG-HIVST) kits has been proposed to enhance paediatric HIV case finding and contribute toward ending paediatric HIV/AIDS by 2030. We conducted a systematic review to assess the risks and benefits of CG-HIVST. We searched nine electronic databases and consulted experts to identify relevant articles through 5 February, 2022. Studies comparing CG-HIVST to other testing services among children over 18-months, or to no intervention, were included. Outcomes included uptake, acceptability, diagnostic accuracy, feasibility, HIV positivity, linkage to care, social harm, values and preferences, costs, and cost-effectiveness. Risk of bias was assessed using relevant Cochrane tools and certainty of evidence was evaluated with GRADE. Among 2203 screened articles, nine observational studies from sub-Saharan Africa were included. All studies used and assessed caregiver-assisted testing using oral fluid-based HIVST. In one non-randomized intervention study of 6062 children, overall CG-HIVST uptake was lower than other standard testing services (3.30% vs. 56.71%). In the same study, HIV positivity following CG-HIVST appeared lower or comparable to standard testing (RR = 0.44; 95% CI: 0.06, 3.20). Two single-arm studies reported high linkage to confirmatory testing (97.48%) and treatment initiation (97.7%) among children reported positive with CG-HIVST. Pooled positive predictive value was 36.72% across three non-randomized intervention studies. Reported social harms were rare, and acceptability appeared high among caregivers taking up the intervention, but feasibility was unclear as some reported anxiety in relation to reactive results. Evidence was appraised very low certainty. Average CG-HIVST costs varied widely and were consistently higher than standard testing services. CG-HIVST may be acceptable, but feasibility remains uncertain with potential higher costs. Current evidence favours standard testing for uptake and positivity. Low positive predictive values raise concerns about false positives and potential harm. Programmes should prioritize evidence-based approaches for paediatric case-finding, while research to fully evaluate this approach continues.

IntroductionInfection causes a vast burden of disease, with significant mortality, morbidity and costs to health-care systems. However, identifying the pathogen causative infection can be challenging, resulting in high use of broad-spectrum antibiotics, much of which may be inappropriate. Novel metagenomic methods have potential to rapidly identify pathogens, however their clinical utility for many infections is currently unclear. Outcome from infection is also impacted by the effectiveness of immune responses, which can be impaired by age, co-morbidity and the infection itself. The aims of this study are twofold: To compare diversity of organisms identified and time-to-result using metagenomic methods versus traditional culture -based techniques, to explore the potential clinical role of metagenomic approaches to pathogen identification in a range of infections.To characterise the ex vivo function of immune cells from patients with acute infection, exploring host and pathogen-specific factors which may affect immune function and overall outcomes.MethodsThis is a prospective observational study of patients with acute infection. Patients with symptoms suggestive of an acute infection will be recruited, and blood and bodily fluid relevant to the site of infection collected (for example, sputum and naso-oropharyngeal swabs for respiratory tract infections, or urine for a suspected urinary tract infection). Metagenomic analysis of samples will be compared to traditional microbiology, alongside the antimicrobials received. Blood and respiratory samples such as bronchoalveolar lavage will be used to isolate immune cells and interrogate immune cell function. Where possible, similar samples will be collected from matched participants without a suspected infection to determine the impact of infection on both microbiome and immune cell function.

This study examined how single nucleotide polymorphisms (SNPs) related to choline synthesis and metabolism, processes largely regulated by estrogen, influenced hippocampal volume and neuropsychological function following menopause. We investigated the effect of choline kinase alpha (CHKA) genotype on brain volume and neuropsychological performance in postmenopausal women. The effect alleles of certain CHKA SNPs (rs6591331 T, rs10791957 A) are associated with varied responses to choline deficiency and delegation of choline to physiological pathways. The presence of these alleles was hypothesized to correlate with worse cognitive performance in women after menopause. Results from structural MRI scans revealed larger right hippocampal volumes in subjects with a T/T CHKA rs6591331 genotype compared to A/A subjects. Delayed memory scores from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were lower in subjects with T/T genotypes compared to those with the A/T genotype and the A/A genotype. Based on these findings, we proposed a CHKA-dependent mechanism present within the brain to compensate for the decreased estrogen and biosynthesized choline associated with menopause.

BackgroundMothers of very preterm (