The acceptability of implementation of group B Streptococcus testing: Perspectives from women and health professionals in the GBS3 trial: A qualitative study.

OBJECTIVE: To determine the acceptability of different methods of routine testing for group B Streptococcus (GBS) colonisation to pregnant women and health care professionals (HCPs), and to examine barriers and facilitators to their implementation. DESIGN: Qualitative study, embedded in a cluster randomised trial SETTING: Four NHS maternity units participating in the GBS3 Trial: two conducting routine antenatal enriched culture medium (ECM) testing; and two using routine rapid intrapartum testing. Sample 39 women and 25 HCPs purposively sampled to ensure representation of women with various birthing experiences and different professions. Methods Women were interviewed approximately 12 weeks postpartum by telephone or online video call, using a semi-structured topic guide. HCPs were interviewed during the testing period of the trial. Interviews were transcribed for thematic analysis and summarised using the framework method. RESULTS: Four categories of interest emerged: (1) views of routine testing; (2) acceptability of the testing procedure; (3) preferences on the types of test; (4) improving the testing procedure. Routine GBS testing was well received by both women and HCPs. Most participants found the procedure acceptable and were willing to receive the offer of testing in the future. Preferences for different testing methods varied, with participants emphasising the importance of evidence and informed choice. CONCLUSIONS: Routine GBS testing is acceptable to most women and HCPs. Areas for consideration and the practicalities of implementing testing in maternity services are highlighted.

The non-inferiority of piperonyl-butoxide Yorkool® G3 insecticide-treated nets compared to Olyset®Plus measured by Anopheles arabiensis mortality in experimental huts in Tanzania.

BACKGROUND: Non-inferiority trials are recommended by the World Health Organization (WHO) to demonstrate that health products show comparable efficacy to that of existing standard of care. As part of the WHO Global Malaria Programme (GMP) process of assessment of malaria vector control products, a second-in-class insecticide-treated net (ITN) must be shown to be non-inferior to a first-in-class product based on mosquito mortality. The public health impact of the first-in-class pyrethroid-piperonyl butoxide (PBO) ITN, Olyset® Plus, has been demonstrated in epidemiological trials in areas with insecticide-resistant mosquitoes, but there is a need to determine the efficacy of other pyrethroid-PBO nets to ensure timely market availability of nets in order to increase access to ITNs. The non-inferiority of a deltamethrin-PBO ITN Yorkool® G3 was evaluated entomologically against Olyset® Plus in experimental huts in Tanzania, following WHO guidelines for non-inferiority trials. METHODS: The trial of the two pyrethroid-PBO ITNs was conducted in experimental huts in Lupiro, Tanzania, using a randomized 7 × 7 Latin square block design. The study ran for 49 nights in 14 huts assessing the mosquito mortality and blood-feeding of wild, free-flying, pyrethroid-resistant Anopheles arabiensis. Using the non-inferiority approach, the comparative efficacy (primary endpoint was mosquito mortality at 24 h and secondary endpoint was blood-feeding) of unwashed and 20 times field-washed pyrethroid-PBO Yorkool® G3 ITNs, were compared with the first-in-class product Olyset® Plus and against a pyrethroid-only ITN, PermaNet® 2.0 ITNs, as a standard comparator. RESULTS: The experimental hut trial demonstrated non-inferiority and superiority of Yorkool® G3 to Olyset® Plus based on mosquito mortality [51% vs. 39%, OR 1.68 (95% CI 1.50-1.88)], given that lower 95% CI exceeded 0.74 (delta of 39%) and the margin of no difference (1). Blood-feeding inhibition was high for all treated ITNs (> 90%) and Yorkool® G3 was non-inferior to Olyset® Plus [4% vs. 2%, OR 1.81 (95% CI 1.46-2.39)], given that upper 95% CI was less than 4.85 (delta of 4%). The pyrethroid-PBO ITNs were superior to the pyrethroid-only net, PermaNet® 2.0, as determined by both the proportion of mortality and blood-feeding of mosquitoes (p-value < 0.05). CONCLUSION: Yorkool® G3 ITNs demonstrated non-inferiority to the first-in-class Olyset® Plus and superiority over the standard pyrethroid-only ITN, PermaNet® 2.0 as measured by mortality and blood-feeding inhibition of wild pyrethroid-resistant An. arabiensis mosquitoes. Yorkool® G3 ITNs are potential tools for the control of metabolic insecticide-resistant malaria vectors, and their market availability will contribute to the cost-effective selection of ITNs by malaria control programmes to improve population access to ITNs.

Effectiveness of surgical interventions for managing obesity in children and adolescents: A systematic review and meta-analysis framed using minimal important difference estimates based on GRADE guidance to inform a clinical practice guideline.

OBJECTIVE: To summarize the literature on bariatric surgery for managing pediatric obesity, including intervention effects to improve patient-reported outcome measures (PROMs), cardiometabolic risk factors, anthropometry, and assess adverse events (AEs). METHODS: Eligible studies were published between January 2012 and January 2022 and included randomized controlled trials (RCTs) and observational (controlled and uncontrolled) studies before and after surgery with a mean age <18 years old. Outcomes and subgroups were selected a priori by stakeholders; estimates of effect for outcomes were presented relative to minimal important differences (MIDs) and GRADE certainty of evidence. We examined data on PROMs, cardiometabolic risk factors, anthropometry, and AEs. Subgroup analyses examined outcomes by follow-up duration and surgical technique, when possible. RESULTS: Overall, 63 publications (43 original studies) met our inclusion criteria (n = 6128 participants; 66% female). Studies reported six different surgical techniques that were evaluated using uncontrolled single arm observational (n = 49), controlled observational (n = 13), and RCT (n = 1) designs. Most studies included short-term follow-up (<18 months) only. PROMs were measured in 12 (28%) studies. Surgery led to large improvements in health-related quality of life compared to baseline and control groups, and moderate to very large improvements in cardiometabolic risk factors compared to baseline. Large to very large improvements in BMIz were noted compared to baseline across all follow-up periods. There was limited evidence of AEs with most reporting mild or non-specific AEs; serious AEs were uncommon. CONCLUSION: Bariatric surgery demonstrated primarily moderate to very large improvements across diverse outcomes with limited evidence of AEs, albeit with low to moderate certainty of evidence.

Technology-Based Interventions in Tobacco Use Treatment Among People Who Identify as African American/Black, Hispanic/Latina/o, and American Indian/Alaska Native: Scoping Review.

BACKGROUND: Although tobacco use has significantly declined in the general population, traditional tobacco use treatment uptake and success rates remain disproportionately low among people who identify as African American/Black, Hispanic/Latina/o, and American Indian/Alaska Native. Technology-based interventions (TBIs) for tobacco use are promising alternatives to traditional tobacco use treatments. OBJECTIVE: This scoping review aims to investigate the extent to which the use of digital TBIs in tobacco use treatment research promotes health equity among people who identify as African American/Black, Hispanic/Latina/o, and American Indian/Alaska Native. METHODS: This scoping review identifies US-based studies (between January 2000 and March 2021) that enlist TBIs for tobacco use treatment and include people who identify as African American/Black, Hispanic/Latina/o, and American Indian/Alaska Native at ≥50% of the sample when combined; features studies that are also race and ethnicity conscious; and highlights health equity-promoting insights from included studies. RESULTS: In 85% (22/26) of the studies, the largest proportion of the sample was African American/Black, most participants had low socioeconomic status, and recruitment was most commonly from medical settings. In total, 58% (15/26) of the studies were race and ethnicity conscious, and 67% (10/15) of these studies sought to partner with potential end users. An array of TBIs were represented; however, SMS text messaging was most prevalent. Most TBIs were combined with other evidence-based intervention components (eg, nicotine replacement therapy). Approximately one-third of the studies (8/26, 31%) required participants to have their own device or internet access. The majority were underpowered to detect substantial differences. CONCLUSIONS: The modest number of studies, particularly for persons who identify as Hispanic/Latina/o and American Indian/Alaska Native, demonstrates the limited application of TBIs for tobacco use and that additional research is needed to determine the extent to which TBIs for tobacco use promote health equity among these populations. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/34508.

Comparing rates of recurrent infection for first occurrence of Clostridioides difficile between tapered oral vancomycin and standard vancomycin: a retrospective, propensity matched cohort study.

OBJECTIVE: To compare rates of Clostridioides difficile infection (CDI) recurrence following initial occurrence treated with tapered enteral vancomycin compared to standard vancomycin. DESIGN: Retrospective cohort study. SETTING: Community health system. PATIENTS: Adults ≥18 years of age hospitalized with positive C. difficile polymerase chain reaction or toxin enzyme immunoassay who were prescribed either standard 10-14 days of enteral vancomycin four times daily or a 12-week tapered vancomycin regimen. METHODS: Retrospective propensity score pair matched cohort study. Groups were matched based on age < or ≥ 65 years and receipt of non-C. difficile antibiotics during hospitalization or within 6 months post-discharge. Recurrence rates were analyzed via logistic regression conditioned on matched pairs and reported as conditional odds ratios. The primary outcome was recurrence rates compared between standard vancomycin versus tapered vancomycin for treatment of initial CDI. RESULTS: The CDI recurrence rate at 6 months was 5.3% (4/75) in the taper cohort versus 28% (21/75) in the standard vancomycin cohort. The median time to CDI recurrence was 115 days versus 20 days in the taper and standard vancomycin cohorts, respectively. When adjusted for matching, patients in the taper arm were less likely to experience CDI recurrence at 6 months when compared to standard vancomycin (cOR = 0.19, 95% CI 0.07-0.56, p < 0.002). CONCLUSIONS: Larger prospective trials are needed to elucidate the clinical utility of tapered oral vancomycin as a treatment option to achieve sustained clinical cure in first occurrences of CDI.

Effectiveness of pharmacological interventions for managing obesity in children and adolescents: A systematic review and meta-analysis framed using minimal important difference estimates based on GRADE guidance to inform a clinical practice guideline.

OBJECTIVE: To summarize the literature on pharmacotherapy for managing paediatric obesity. METHODS: A systematic review and meta-analysis were conducted of randomized controlled trials (RCTs) with <18-year-olds of pharmacotherapeutic agents published up to November 2022. Estimates of effect for outcomes were presented relative to minimal important differences and GRADE certainty of evidence. We examined data on patient/proxy-reported outcome measures (PROMs), cardiometabolic risk factors, anthropometry and adverse events (AEs). RESULTS: Overall, 35 RCTs were included. Trials examined metformin (n = 26), glucagon-like peptide-1 receptor agonists (GLP1RAs) (n = 7) and a lipase inhibitor (orlistat; n = 2). Intervention duration varied (3-24 months). Metformin had little to no benefit on PROMs (e.g., health-related quality of life [HRQoL]; 6 RCTs), moderate reductions in triglycerides, a moderate decline in insulin resistance, a small to moderate decline in BMI z-score (BMIz) and a moderate increase in mild to moderate gastrointestinal AEs. Response to GLP1RAs was heterogeneous and results of subgroup analysis demonstrated variability of impact. Liraglutide (2 RCTs) resulted in a small reduction in HOMA-IR and BMIz, but little to no benefit on other outcomes. Exenatide (4 RCTs) had a moderate reduction on blood pressure and a small decrease in BMIz with little to no benefit on other outcomes. Semaglutide (1 RCT) had a small benefit on HRQoL, a small reduction on SBP, a moderate reduction on total cholesterol and LDL-cholesterol, a large reduction on triglyceride, and a very large decline in BMIz accompanied by a small increase in mild to moderate gastrointestinal AEs. Orlistat had a moderate reduction in DBP and little to no benefit in other outcomes measured, but had a very large increased risk of mild to moderate gastrointestinal AEs. Serious AEs were rare and for interventions with sufficent AE reporting, were considered not likely attributable to the interventions. CONCLUSION: Few studies examined the impact of pharmacotherapy on PROMs. There is evidence that metformin and GLP1RAs lead to important improvements in cardiometabolic and anthropometric outcomes while accompanied by mild to moderate AEs. Long-term effectiveness and safety of GLP1RAs remain to be evaluated.

Bilateral Blistering Rash Following Gastric Bypass Procedure and Mushroom Soup Diet: Hepatitis C Virus-Seronegative Necrolytic Acral Erythema.

Necrolytic acral erythema (NAE) is an uncommon cutaneous disorder characterized by a symmetric acral distribution of erythematous plaques with underlying epidermal necrosis. While typically presenting in the context of hepatitis C virus (HCV) infection, NAE can also present secondary to nutritional deficiency or systemic disease. We present a case of NAE in a 66-year-old patient with no history of HCV infection status post gastric bypass who had a three-month history of eating only mushroom soup. The patient underwent a punch biopsy and was tested for a variety of nutritional deficiencies. Biopsy demonstrated partial necrosis of the upper epidermis, with subjacent re-epithelialization, squamatization, and vacuolopathy of the basal epidermis. He was treated with zinc replacement therapy after initial trials of tacrolimus and clobetasol were unsuccessful. At follow-up, he had significant improvement of the lesions. This case provides an example of an atypical presentation of NAE in the absence of HCV infection that presented as a complication of gastric bypass-associated nutritional deficiency.

Persistent Autonomic and Immunologic Abnormalities in Neurologic Post-Acute Sequelae of SARS-CoV2 Infection.

OBJECTIVES: After acute coronavirus disease-2019 (COVID-19), people often experience fatigue, "brain fog," or other central neurologic symptoms (neuro-post-acute SARS-CoV2, or "Neuro-PASC"). In this observational study we evaluated whether abnormalities noted on initial evaluation persist after at least another year. METHODS: Neuro-PASC research participants who had undergone comprehensive inpatient testing at the NIH Clinical Center returned after at least 1 year for follow-up assessments including symptoms rating scales, MRI, lumbar puncture for tests of the CSF, physiologic recordings during the Valsalva maneuver and head-up tilting (with serial plasma catechols and cardiac Doppler ultrasound during the tilting), blood volume measurement, skin biopsies to examine sympathetic innervation, and blood sampling for neuroendocrine and immunologic measures. RESULTS: 7 patients with Neuro-PASC (6 women, age range 42-63 years) underwent follow-up testing. 71% of initially abnormal test results remained abnormal at follow-up, including the pattern of CSF and serum oligoclonal bands, CSF indices of central catecholamine deficiency, baroreflex-cardiovagal dysfunction, the occurrence of tilt-evoked sudden hypotension, white matter hyperintensities on MRI, and adaptive responses in CSF. DISCUSSION: In Neuro-PASC most of the autonomic and immunologic abnormalities found initially are still present after more than a year.

"Losing access to outdoor spaces was the biggest challenge for children to be healthy": pandemic restrictions and community supports for children's movement in Nova Scotia.

Introduction: Health-focused communities can promote physical activity for children by providing them with safe and supportive environments to move. Across the COVID-19 pandemic many community spaces and services were closed due to public health restrictions. During the pandemic, Atlantic Canada uniquely implemented an agreement between four provinces to restrict travel and reduce the spread of the virus. The "Atlantic bubble" led to fewer cases of COVID-19 and restrictions to community spaces and services. With restrictions now removed, community spaces and services likely play a critical role in facilitating the recalibration of children's movement. Perspectives from families who experienced the "Atlantic bubble" may offer valuable insights to the use of these spaces during and after the removal of restrictions. Objective: This study explored the role of community spaces and services on their child's physical activity across the COVID-19 pandemic from the perspectives of Nova Scotia caregivers. Methods: We employed a qualitative description approach and conducted semi-structured interviews with 14 caregivers of children aged 5-11 years who lived in Nova Scotia, Canada. Interviews were transcribed verbatim and analyzed using reflexive thematic analysis. Results: Four themes were generated: (1) Public health restrictions limited community movement behaviors and social connections, (2) Spaces, locations, and environments influenced how families experienced physical activity during public health restrictions, (3) Virtual realities: screens supported a new sense of community for children throughout the pandemic, and (4) "Facilitated" and "forced adaptability": public health restrictions changed family dynamics, routines, and movement behaviors. Conclusion: Despite living in the "Atlantic bubble," Nova Scotian caregivers shared that COVID-19 related public health restrictions shifted their family's dynamics, routines, and ability to engage in physical activity within their communities. Community spaces and services can be leveraged to recalibrate children's movement as pandemic-related restrictions are reduced. In future public health crises, community spaces and services should remain in place to whatever extent possible to reduce the collateral consequences of public health restrictions on children's health.

Preliminary evaluation of a novel method for computed tomography quantification of lumbosacral articular process displacement in dogs with and without degenerative lumbosacral stenosis.

Objective: This study aimed to describe the diagnostic discrimination and reliability of a novel technique for quantifying lumbosacral articular process displacement (LSAPD) on dorsal plane computed tomography (DPCT) imaging in dogs with and without degenerative lumbosacral stenosis (DLSS). Study design: DPCT surveys of the lumbosacral vertebral column were performed with dogs positioned in extension and flexion. LSAPD is defined as the distance between the cranial aspects of the L7 and S1 articular processes. The LSAPD ratio is identified by dividing the LSAPD by the length of the L7 articular process. Intraclass correlation coefficients (ICCs) for intra- and inter-observer reliability were calculated, and logistic regressions were used to test for the association of LSAPD and LSAPD ratio with odds of DLSS. Significance was set at 0.05. Receiver operator characteristic (ROC) curves were calculated to determine diagnostic discrimination and optimal cutoff for LSAPD and LSAPD ratio in the diagnosis of DLSS. Results: Intra- and inter-observer reliabilities were excellent for most measurements. In the current cohort, excluding covariates, the area under the curve (AUC) (95%CI) for LSAPD and LSAPD ratio measured in a flexed position were both 0.89 (0.82-0.96), suggesting potentially excellent discrimination for using this measurement as a marker for diagnosing DLSS, pending further studies. The cutoffs for flexed LSAPD and LSAPD ratio that maximizes Youden's index were ≥ 1.2 mm and ≥ 9%, respectively. When age and weight were subsequently included as covariates in a multivariable analysis, a significant relationship between LSAPD or LSAPD ratio and odds of diagnosis of DLSS was not demonstrated, suggesting the need for a larger sample size. Conclusion: The results of this study suggest that measurements of LSAPD and LSAPD ratio on DPCT are feasible and reliable, although their diagnostic discrimination in DLSS should be evaluated further in future prospective studies.

A review of selective indoor residual spraying for malaria control.

BACKGROUND: Indoor residual spraying (IRS) is one of the most effective malaria control tools. However, its application has become limited to specific contexts due to the increased costs of IRS products and implementation programmes. Selective spraying-selective spray targeted to particular areas/surfaces of dwellings-has been proposed to maintain the malaria control and resistance-management benefits of IRS while decreasing the costs of the intervention. METHODS: A literature search was conducted to find (1) studies that assessed the resting behaviour of Anopheles mosquitoes and (2) studies that evaluated the impact of selective spraying on entomological and malaria outcomes. Additional articles were identified through hand searches of all references cited in articles identified through the initial search. A cost model was developed from PMI VectorLink IRS country programmes, and comparative cost analysis reports to describe the overall cost benefits of selective IRS. RESULTS: In some studies, there appeared to be a clear resting preference for certain Anopheles species in terms of the height at which they rested. However, for other species, and particularly the major African malaria vectors, a clear resting pattern was not detected. Furthermore, resting behaviour was not measured in a standardized way. For the selective spray studies that were assessed, there was a wide range of spray configurations, which complicates the comparison of methods. Many of these spray techniques were effective and resulted in reported 25-68% cost savings and reduced use of insecticide. The reported cost savings in the literature do not always consider all of the IRS implementation costs. Using the IRS cost model, these savings ranged from 17 to 29% for programs that targeted Anopheles spp. and 18-41% for programmes that targeted Aedes aegypti. CONCLUSIONS: Resting behaviour is generally measured in a simplistic way; noting the resting spot of mosquitoes in the morning. This is likely an oversimplification, and there is a need for better monitoring of resting mosquitoes. This may improve the target surface for selective spray techniques, which could reduce the cost of IRS while maintaining its effectiveness. Reporting of cost savings should be calculated considering the entire implementation costs, and a cost model was provided for future calculations.

Field evaluation of a volatile pyrethroid spatial repellent and etofenprox treated clothing for outdoor protection against forest malaria vectors in Cambodia.

Cambodia's goal to eliminate malaria by 2025 is challenged by persistent transmission in forest and forest fringe areas, where people are exposed to Anopheles mosquito bites during the day and night. Volatile pyrethroid spatial repellents (VPSRs) and insecticide-treated clothing (ITC) could address these gaps. This study evaluated the outdoor application of one passive transfluthrin-based VPSR, four etofenprox-ITCs paired with a picaridin topical repellent, and a combination of VPSR and ITC against wild Anopheles landing in Cambodia. A 7 × 7 Latin-square study was conducted over 49 collection nights in temporary open structures in Mondulkiri Province. All interventions substantially reduced Anopheles landing, with protective efficacy ranging from 61 to 95%. Mathematical modeling showed significant reductions in vectoral capacity, especially with the combined ITC and VPSR and VPSR alone, albeit with decreased effectiveness over time. These interventions have the potential to reduce outdoor and daytime Anopheles biting, offering valuable contributions to malaria elimination efforts in Cambodia and the Greater Mekong Subregion, contingent upon achieving effective coverage and adherence.

Additional blood meals increase sporozoite infection in Anopheles mosquitoes but not Plasmodium falciparum genetic diversity.

The availability of nutrients from mosquito blood meals accelerates the development of Plasmodium falciparum laboratory strains in artificially infected Anopheles gambiae mosquitoes. The impact of multiple blood meals on the number of P. falciparum genotypes developing from polyclonal natural human malaria infections (field-isolates) remains unexplored. Here, we experimentally infect An. gambiae with P. falciparum field-isolates and measure the impact of an additional non-infectious blood meal on parasite development. We also assess parasite genetic diversity at the blood stage level of the parasite in the human host and of the sporozoites in the mosquito. Additional blood meals increase the sporozoite infection prevalence and intensity, but do not substantially affect the genetic diversity of sporozoites in the mosquito. The most abundant parasite genotypes in the human blood were transmitted to mosquitoes, suggesting that there was no preferential selection of specific genotypes. This study underlines the importance of additional mosquito blood meals for the development of parasite field-isolates in the mosquito host.

Occupational exposure to malaria, leishmaniasis and arbovirus vectors in endemic regions: A systematic review.

Vector-borne diseases, including dengue, leishmaniasis and malaria, may be more common among individuals whose occupations or behaviours bring them into frequent contact with these disease vectors outside of their homes. A systematic review was conducted to ascertain at-risk occupations and situations that put individuals at increased risk of exposure to these disease vectors in endemic regions and identify the most suitable interventions for each exposure. The review was conducted in accordance with PRISMA guidelines on articles published between 1945 and October 2021, searched in 16 online databases. The primary outcome was incidence or prevalence of dengue, leishmaniasis or malaria. The review excluded ecological and qualitative studies, abstracts only, letters, commentaries, reviews, and studies of laboratory-acquired infections. Studies were appraised, data extracted, and a descriptive analysis conducted. Bite interventions for each risk group were assessed. A total of 1170 articles were screened and 99 included. Malaria, leishmaniasis and dengue were presented in 47, 41 and 24 articles, respectively; some articles presented multiple conditions. The most represented populations were soldiers, 38% (43 of 112 studies); refugees and travellers, 15% (17) each; migrant workers, 12.5% (14); miners, 9% (10); farmers, 5% (6); rubber tappers and missionaries, 1.8% (2) each; and forest workers, 0.9% (1). Risk of exposure was categorised into round-the-clock or specific times of day/night dependent on occupation. Exposure to these vectors presents a critical and understudied concern for outdoor workers and mobile populations. When devising interventions to provide round-the-clock vector bite protection, two populations are considered. First, mobile populations, characterized by their high mobility, may find potential benefits in insecticide-treated clothing, though more research and optimization are essential. Treated clothing offers personal vector protection and holds promise for economically disadvantaged individuals, especially when enabling them to self-treat their clothing to repel vectors. Secondly, semi-permanent and permanent settlement populations can receive a combination of interventions that offer both personal and community protection, including spatial repellents, suitable for extended stays. Existing research is heavily biased towards tourism and the military, diverting attention and resources from vulnerable populations where these interventions are most required like refugee populations as well as those residing in sub-Saharan Africa.

Germ line ERG haploinsufficiency defines a new syndrome with cytopenia and hematological malignancy predisposition.

ABSTRACT: The genomics era has facilitated the discovery of new genes that predispose individuals to bone marrow failure (BMF) and hematological malignancy (HM). We report the discovery of ETS-related gene (ERG), a novel, autosomal dominant BMF/HM predisposition gene. ERG is a highly constrained transcription factor that is critical for definitive hematopoiesis, stem cell function, and platelet maintenance. ERG colocalizes with other transcription factors, including RUNX family transcription factor 1 (RUNX1) and GATA binding protein 2 (GATA2), on promoters or enhancers of genes that orchestrate hematopoiesis. We identified a rare heterozygous ERG missense variant in 3 individuals with thrombocytopenia from 1 family and 14 additional ERG variants in unrelated individuals with BMF/HM, including 2 de novo cases and 3 truncating variants. Phenotypes associated with pathogenic germ line ERG variants included cytopenias (thrombocytopenia, neutropenia, and pancytopenia) and HMs (acute myeloid leukemia, myelodysplastic syndrome, and acute lymphoblastic leukemia) with onset before 40 years. Twenty ERG variants (19 missense and 1 truncating), including 3 missense population variants, were functionally characterized. Thirteen potentially pathogenic erythroblast transformation specific (ETS) domain missense variants displayed loss-of-function (LOF) characteristics, thereby disrupting transcriptional transactivation, DNA binding, and/or nuclear localization. Selected variants overexpressed in mouse fetal liver cells failed to drive myeloid differentiation and cytokine-independent growth in culture and to promote acute erythroleukemia when transplanted into mice, concordant with these being LOF variants. Four individuals displayed somatic genetic rescue by copy neutral loss of heterozygosity. Identification of predisposing germ line ERG variants has clinical implications for patient and family diagnoses, counseling, surveillance, and treatment strategies, including selection of bone marrow donors and cell or gene therapy.

Comparison of the Trapping Efficacy of Locally Modified Gravid Aedes Trap and Autocidal Gravid Ovitrap for the Monitoring and Surveillance of Aedes aegypti Mosquitoes in Tanzania.

The study assessed the trapping efficacy of locally modified (1) Gravid Aedes Trap (GAT) lined with insecticide-treated net (ITN) as a killing agent and (2) Autocidal Gravid Ovitrap (AGO) with sticky board in the semi-field system (SFS) and field setting. Fully balanced Latin square experiments were conducted to compare GAT lined with ITN vs. AGO, both with either yeast or grass infusion. Biogent-Sentinel (BGS) with BG-Lure and no CO2 was used as a standard trap for Aedes mosquitoes. In the SFS, GAT outperformed AGO in collecting both nulliparous (65% vs. 49%, OR = 2.22, [95% CI: 1.89-2.60], p < 0.001) and gravid mosquitoes (73% vs. 64%, OR = 1.67, [95% CI: 1.41-1.97], p < 0.001). Similar differences were observed in the field. Yeast and grass infusion did not significantly differ in trapping gravid mosquitoes (OR = 0.91, [95% CI: 0.77-1.07], p = 0.250). The use of ITN improved mosquito recapture from 11% to 70% in the SFS. The same trend was observed in the field. Yeast was chosen for further evaluation in the optimized GAT due to its convenience and bifenthrin net for its resistance management properties. Mosquito density was collected when using 4× GATs relative to BGS-captured gravid mosquitoes 64 vs. 58 (IRR = 0.82, [95% CI: 0.35-1.95], p = 0.658) and showed no density dependence. Deployment of multiple yeast-baited GAT lined with bifenthrin net is cost-effective (single GAT < $8) compared to other traps such as BGS ($160).

The acceptability of group B streptococcal bacteria (GBS) testing to women, including self-swabbing procedures: A qualitative study.

BACKGROUND: Group B streptococcus (GBS) is a bacterium carried by 20-25 % of pregnant women in the UK, which can be transmitted from pregnant women to their babies at the time of birth. Women can be tested for GBS in pregnancy using a vaginal-rectal swab, however, this testing is currently not routinely offered in the UK. A large clinical trial is underway to determine the clinical and cost-effectiveness of routine testing (ISRCTN reference number ISRCTN49639731). A crucial part of understanding whether this type of test should be implemented is women's views on the acceptability of being offered GBS tests, their preferences towards testing procedures and their willingness to receive these tests. AIM: To explore women's views on the acceptability of different methods of Group B streptococcal bacteria (GBS) testing in pregnancy, including self-swabbing procedures. METHODS: A convenience sample of 19 women (5 pregnant and 14 postpartum) were interviewed using a semi-structured interview guide. Interviews were transcribed and analysed using systematic thematic analysis. RESULTS: Findings show that many of the women interviewed were not concerned about being offered a GBS test, were willing to provide a sample and felt positive towards samples being taken to detect GBS. Women varied in their preferences on the best time for sampling. Some thought being approached during pregnancy gave them time to understand the purpose of testing, prepare for what may happen next and ask questions about potential treatment if needed. Others thought labour was a good time to provide accurate results on GBS carriage at birth and reduce unnecessary worry during pregnancy. However, women were concerned that they may be unable to make an informed decision in labour due to time, pain and the prospect of birthing quickly. Women perceived clinician swabbing as more accurate than self-sampling; however, many thought clinician swabbing might be embarrassing so self-swabs should be available to increase uptake for some women. CONCLUSIONS: Overall, women thought both pregnancy and labour were acceptable times to test for GBS. The majority found both clinician and self-swabbing procedures acceptable; however, many had a preferred swabbing option and thought women should be given the choice of the swabbing procedure most acceptable to them. It is important that women are given information about GBS testing and its procedures in pregnancy regardless of when the GBS swabbing is performed.

Clinical research self-efficacy in academic veterinary clinicians in the United States.

OBJECTIVE: Clinical research is a growing part of the academic clinician's job, and documenting areas of low self-efficacy can inform training initiatives. SAMPLE: 182 US academic veterinary clinicians. METHODS: A survey of academic veterinary clinicians was distributed to 31 US institutions. Self-efficacy was assessed with a modified Clinical Research Appraisal Instrument-12. The relationship between research self-efficacy and completion of formal research training and years of experience was evaluated. RESULTS: Respondents were predominantly junior to midcareer faculty. The lowest reported confidence was in performing advanced statistical analyses (3; 0 to 10). Other low-confidence tasks included designing a qualitative methods study (4; 0 to 10), terminating a collaboration that isn't working (5; 0 to 10), describing a funding agency's review/award process (5; 0 to 10), establishing a timeline for a grant application (5; 0 to 10), establishing collaborator and consultant agreements (5; 0 to 10), and asking staff to leave the project team (5; 0 to 10). Completion of a formal research training program was significantly associated with improved self-efficacy in many tasks. Years of experience was also associated, especially in project management and interpersonal interactions. CLINICAL RELEVANCE: These results highlight the need for targeted training opportunities for academic veterinary clinicians in biostatistical support, qualitative study design methods, and aspects of communication and interpersonal skills that are important for developing and leading effective research teams. Range of confidence suggests that development opportunities in all domains will improve self-efficacy for some clinicians. Future studies should focus on the impact of formal training sessions on various domains of self-efficacy and on targeted mentoring in supporting confidence in more experiential learning domains.