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Myelodysplastic syndromes/neoplasms (MDS) are heterogeneous stem cell malignancies characterized by poor prognosis and no curative therapies outside of allogeneic hematopoietic stem cell transplantation. Despite some recent approvals by the United States Food and Drug Administration (FDA), (e.g., luspatercept, ivosidenib, decitabine/cedazuridine and imetelstat), there has been little progress in the development of truly transformative therapies for the treatment of patients with MDS. Challenges to advancing drug development in MDS are multifold but may be grouped into specific categories including criteria for risk stratification and eligibility, response definitions, time-to-event endpoints, transfusion endpoints, functional assessments, and biomarker development. Strategies to address these challenges and optimize future clinical trial design for patients with MDS are presented here., (Copyright © 2024 American Society of Hematology.)

Objective: To examine the factors that make such programs successful, this systematic review compared the outcomes of children's participation in cooking interventions based on intervention characteristics., Design: Systematic review of randomized controlled trials of children's participation in cooking interventions published between 1998 and 2022 guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement., Setting: All settings PARTICIPANTS: Children and parents., Main Outcome Measures: Cooking skills, food acceptance and dietary behavior., Analysis: Systematic search of 1,104 articles and review of 23 studies (42 articles) meeting inclusion criteria., Results: Interventions varied in participant age, settings, cooking sessions, and program length. Knowledge of cooking skills, self-efficacy, and child cooking involvement were the most frequent positive outcomes; improvements in dietary intake were rarely achieved. Seven studies had a high rating for research quality., Conclusion and Implications: Lack of standardized assessment, large variability in program characteristics, and insufficient intervention description made it difficult to discern best practices for children's cooking programs. Improvements in intervention development and measurement instruments are needed. Interventions that include hands-on cooking lessons seem promising in improving knowledge and self-efficacy; however, further exploration is required on the factors that make cooking programs successful in the long term., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction. Strongyloides stercoralis , the human threadworm, is a parasitic nematode with global distribution, estimated to infect over 600 million people. Chronic infection is often asymptomatic, but hyperinfection and dissemination syndromes can occur in the immunosuppressed with high case fatality rates. Whilst strongyloidiasis is endemic in Fiji, its prevalence in Fijian migrant groups in the UK is unknown. Gap Statement. No previous studies have been conducted on the prevalence of Strongyloides and other gastrointestinal parasites (GIPs) in Fijian migrants to the UK. Aim. We conducted a cross-sectional study of the prevalence of GIPs in a Fijian migrant population. Methodology. Participants completed a questionnaire on residence, travel and clinical symptoms and were asked to provide a serum sample for S. stercoralis IgG ELISA, venous blood samples for eosinophil count and a faecal sample for charcoal culture, multiplex real-time PCR (rtPCR) and microscopy after formalin-ethyl acetate concentration. Sequencing was performed on pooled Strongyloides larvae for nuclear 18S rRNA hyper-variable regions (HVRs) I and IV. Results. A total of 250 participants (94% male) with median (range) age 37 (20-51) years entered the study, 15 (1-24) years since leaving Fiji. S. stercoralis IgG ELISA was positive in 87/248 (35.1 %) and 14/74 (18.9 %) had a GIP detected in faeces. This included 7/74 (9.5 %) with Strongyloides and 5/74 (6.8 %) with hookworms. Dermatological symptoms were more common in those with Strongyloides, and eosinophilia (>0.5×10 9 cells per litre) was present in 55.6% of those with positive S. stercoralis IgG. rtPCR was the most sensitive faecal diagnostic test for Strongyloides and hookworms in faeces. Sequences of nuclear 18S rRNA for HVRs I and IV confirmed the presence of S. stercoralis . Conclusion. This first cross-sectional study in Fijian migrants found a high rate of chronic infection with GIPs, particularly S. stercoralis . Faecal microscopy was insensitive compared to charcoal culture, rtPCR or serology, demonstrating the importance of specialist parasitological tests when investigating people with a suspected chronic infection. Our study highlights an overlooked burden of strongyloidiasis in the UK and has implications for screening and treatment programmes in Fiji and for migrants from Fiji.

Background:  A comprehensive understanding of changes in health-related quality of life after head and neck cancer surgery is necessary for effective preoperative counseling. The goal of this study was to perform a longitudinal analysis of postoperative quality of life outcomes after fibula free flap (FFF) mandible reconstruction., Methods:  A retrospective review was performed for all patients who underwent oncologic mandible reconstruction with an FFF between 2000 and 2021. Completion of at least one postoperative FACE-Q questionnaire was necessary for inclusion. FACE-Q scores were divided into five time periods for analysis. Functional outcomes measured with speech language pathology (SLP) assessments and tracheostomy and gastrostomy tube status were analyzed at three time points., Results:  One hundred and nine patients were included. Of these, 68 patients also had at least one SLP assessment. All outcomes as measured by the various FACE-Q scales did not improve significantly from the immediate postoperative time point to the last evaluated time point ( p  > 0.05). SLP functional outcomes showed some deterioration over time, but these were not significant ( p  > 0.05). The percentage of patients who required a tracheostomy (18 to 2%, p  = 0.002) or gastrostomy tube (25 to 11%, p  = 0.035) decreased significantly from the immediate postoperative time point to the last evaluated time point., Conclusion:  Subjective quality of life outcomes do not change significantly with time after oncologic FFF mandible reconstruction. Reconstructive surgeons can use these results to help patients establish appropriate and achievable quality of life goals after surgery. Further studies are warranted to elucidate the impact of specific relevant clinical variables on postoperative quality of life., Competing Interests: None declared., (Thieme. All rights reserved.)

Disclaimer: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time., Purpose: While the gold standard for vasomotor symptoms remains hormone therapy, prescription menopause therapies are significantly underutilized. Nonhormone therapies represent an alternative treatment modality that may improve access to care for patients who cannot or choose not to take hormones. This review aims to update pharmacists on the evidence behind new-to-market fezolinetant and all other nonhormone prescription treatment options for menopausal vasomotor symptoms., Summary: Prescription nonhormone therapy options for vasomotor symptoms include selective serotonin reuptake inhibitors, including Food and Drug Administration-approved low-dose paroxetine, serotonin-norepinephrine reuptake inhibitors, gabapentin, pregabalin, oxybutynin, and fezolinetant. Evidence supporting the use of these options is summarized in this review. All have an important place in treatment for those unable to take the gold standard of hormone therapy; however, most offer only mild to moderate improvement in symptoms. Fezolinetant has been shown to result in a significant reduction in vasomotor symptom frequency when compared to other nonhormone therapies and was not different when compared to hormone therapies. However, additional studies and efforts to address the affordability of fezolinetant and head-to-head comparisons with other agents are needed., Conclusion: Vasomotor symptoms of menopause can severely impact the health and well-being of individuals. However, treatment of these symptoms is underutilized due to real and perceived drawbacks of therapy. Pharmacists are ideally suited to bridge this gap, but first it is important for pharmacists to be knowledgeable about and comfortable with the evidence supporting all treatment options., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

DIGEST is a validated, open-source method to grade the severity of pharyngeal dysphagia from the modified barium swallow (MBS) study. Dissemination and implementation of DIGEST is rising, making it critical to understand reliability and facilitators of accurate implementation among users. The aim was to assess reliability of the tool among speech-language pathology (SLP) raters practicing at multiple sites before and after review of a DIGEST training manual and evaluate confidence of DIGEST use pre-and post-training. Thirty-two SLPs from 5 sites participated in a blinded longitudinal DIGEST rating study. Raters were provided a standardized training set of MBS (n = 19). Initial SLP ratings (round 1, R1) were followed by a 2-4 week break before raters rated a re-keyed MBS set (round 2, R2). A minimum 4-8 week wash-out period then preceded self-study of the DIGEST training manual which was followed by a final rating (round 3, R3) and a post-manual survey afterwards. Baseline reliability (R1) of overall DIGEST was on average k = 0.70, reflecting agreement in the substantial range. Seventy-five percent of raters (24/32) demonstrated reliability ≥ 0.61 in the substantial to almost perfect range prior to training. Inter-rater reliability significantly improved from R1 to R3 after review of the DIGEST manual, with the largest change in DIGEST-Efficiency (mean change: DIGEST k = .04, p = .009, DIGEST-Safety k = .07, p = 0.03, and DIGEST-Efficiency k = .14, p = 0.009). Although DIGEST reliability at baseline was adequate in the majority of raters, self-study of the DIGEST training manual significantly improved inter-rater reliability and rater confidence using the DIGEST method, particularly when assigning DIGEST-Efficiency grade. These early data show promise that provider training may be useful to aid in fidelity of DIGEST implementation among SLP clinical users with varying DIGEST experience., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Male Genital Schistosomiasis (MGS) remains an often-overlooked chronic sequela of urogenital schistosomiasis in endemic areas of sub-Saharan Africa. As part of a 2-year longitudinal study on Hybridization of UroGenital Schistosomiasis (HUGS) in Malawi, a MGS sub-study was conducted to assess whether hybrid schistosomes were incriminated., Methods: During recruitment, demographic, health and socio-economic data were collected through individual questionnaire interviews in Mthawira community from Nsanje District along Shire River and Samama community from Mangochi District along Lake Malawi shoreline. Urine and semen samples were collected and analysed to determine the identity of schistosome infection. Urine filtration and microscopy, direct microscopy of semen and its sediments (after centrifugation) were performed. Thereafter, the sediments were examined by molecular DNA analysis with a novel two-tube real-time PCR assay. The participants were also screened for Human papilloma virus (HPV) and other sexually transmitted infections (STIs)., Results: Twenty-two men were recruited for the sub-study, 8 in Nsanje District and 14 in Mangochi District, with a median age of 22.0 years. By microscopy, ten (45.7%) participants had Schistosoma ova in their urine, 11 (50.0%) in semen while 16 (72.7%) were positive by real-time PCR. One participant had both S. haematobium and S. mattheei ova in his semen, three showed symptoms, and one had a mixed infection of S. mansoni and possible S. haematobium-S. mattheei hybrid. Twelve men had detectable high-risk HPV serotypes 16, 18 and others while six had Trichomonas vaginalis and other STIs., Conclusion: Zoonotic and hybrid schistosomes can cause MGS similar to human schistosomes, which can be co-infected with HPV and STIs, thereby posing a new challenge in diagnosis, management and control measures in resource poor settings. Increased awareness of these infections among local communities and primary healthcare workers and improvement of disease management are needed and advocated., (© 2024. The Author(s).)

Medical Imaging Phantoms (MIPs) calibrate imaging devices, train medical professionals, and can help procedural planning. Traditional MIPs are costly and limited in customization. Additive manufacturing allows for customizable, patient-specific phantoms. This study examines the CT attenuation characteristics of contrast-injectable, chambered 3D-printed phantoms to optimize tissue-mimicking capabilities. A MIP was constructed from a CT of a complex pelvic tumor near the iliac bifurcation. A 3D reconstruction of these structures composed of three chambers (aorta, inferior vena cava, tumor) with ports for contrast injection was 3D printed. Desired attenuations were 200 HU (arterial I), 150 HU (venous I), 40 HU (tumor I), 150 HU (arterial II), 90 HU (venous II), and 400 HU (tumor II). Solutions of Optiray 350 and water were injected, and the phantom was scanned on CT. Attenuations were measured using ROIs. Mean attenuation for the six phases was as follows: 37.49 HU for tumor I, 200.50 HU for venous I, 227.92 HU for arterial I, 326.20 HU for tumor II, 91.32 HU for venous II, and 132.08 HU for arterial II. Although the percent differences between observed and goal attenuation were high, the observed relative HU differences between phases were similar to goal HU differences. The observed attenuations reflected the relative concentrations of contrast solutions used, exhibiting a strong positive correlation with contrast concentration. The contrast-injectable tumor phantom exhibited a useful physiologic range of attenuation values, enabling the modification of tissue-mimicking 3D-printed phantoms even after the manufacturing process.

Background: Inflammatory bowel disease may affect the pathogenesis and clinicopathologic course of colorectal cancer. We sought to characterize the impact of inflammatory bowel disease on outcomes after colectomy and/or proctectomy for a malignant indication., Methods: Patients diagnosed with colorectal cancer as well as a pre-existing comorbid diagnosis of Crohn's disease or ulcerative colitis between 2018 and 2021 were identified from Medicare claims data. The postoperative textbook outcome was defined as the absence of complications, as well as no extended hospital stay, 90-day readmission, or mortality. Postdischarge disposition and expenditures were also examined., Results: Among 191,684 patients with colorectal cancer, 4,770 (2.5%) had a pre-existing diagnosis of inflammatory bowel disease. Patients with inflammatory bowel disease-associated colorectal cancer were less likely to undergo surgical resection (no inflammatory bowel disease: 47.6% vs inflammatory bowel disease: 42.1%; P < .001). Among patients who did undergo colorectal surgery, individuals with inflammatory bowel disease were less likely to achieve a textbook outcome (odds ratio 0.64 [95% confidence interval 0.58-0.70]). In particular, patients with inflammatory bowel disease had higher odds of postoperative complications (odds ratio 1.24 [1.12-1.38]), extended hospital stay (odds ratio 1.41 [1.27-1.58]), and readmission within 90 days (odds ratio 1.56 [1.42-1.72]) (all P < .05). Patients with inflammatory bowel disease-associated colorectal cancer were less likely to be discharged to their home under independent care (odds ratio 0.77 [0.68-0.87]) and had 12.2% higher expenditures, which correlated with whether the patient had a postoperative textbook outcome., Conclusion: One in 40 patients with colorectal cancer had concomitant inflammatory bowel disease. Inflammatory bowel disease was associated with a lower probability of achieving ideal postoperative outcomes, higher postdischarge expenditure, as well as worse long-term survival after colorectal cancer resection., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Health care providers play a crucial role in increasing overall awareness, screening, and treatment of cancer, leading to reduced cancer mortality. We sought to characterize the impact of provider density on colorectal cancer population-level mortality., Methods: County-level provider data, obtained from the Area Health Resource File between 2016 and 2018, were used to calculate provider density per county. These data were merged with county-level colorectal cancer mortality 2016-2020 data from the Centers for Disease Control and Prevention. Multivariable regression was performed to define the association between provider density and colorectal cancer mortality., Results: Among 2,863 counties included in the analytic cohort, 1,132 (39.5%) and 1,731 (60.5%) counties were categorized as urban and rural, respectively. The colorectal cancer-related crude mortality rate was higher in counties with low provider density versus counties with moderate or high provider density (low = 22.9, moderate = 21.6, high = 19.3 per 100,000 individuals; P < .001). On multivariable analysis, the odds of colorectal cancer mortality were lower in counties with moderate and high provider density versus counties with low provider density (moderate odds ratio 0.97, 95% confidence interval 0.94-0.99; high odds ratio 0.88, 95% confidence interval 0.86-0.91). High provider density remained associated with a lower likelihood of colorectal cancer mortality independent of social vulnerability index (low social vulnerability index and high provider density: odds ratio 0.85, 95% confidence interval 0.81-0.89; high social vulnerability index and high provider density: odds ratio 0.93, 95% confidence interval 0.89-0.98)., Conclusion: Regardless of social vulnerability index, high county-level provider density was associated with lower colorectal cancer-related mortality. Efforts to increase access to health care providers may improve health care equity, as well as long-term cancer outcomes., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The primary goals during acute heart failure (AHF) hospitalization are decongestion and guideline-directed medical therapy (GDMT) optimization. Unlike diuretics or other GDMT, early dapagliflozin initiation could achieve both AHF goals., Objectives: The authors aimed to assess the diuretic efficacy and safety of early dapagliflozin initiation in AHF., Methods: In a multicenter, open-label study, 240 patients were randomized within 24 hours of hospital presentation for hypervolemic AHF to dapagliflozin 10 mg once daily or structured usual care with protocolized diuretic titration until day 5 or hospital discharge. The primary outcome, diuretic efficiency expressed as cumulative weight change per cumulative loop diuretic dose, was compared across treatment assignment using a proportional odds model adjusted for baseline weight. Secondary and safety outcomes were adjudicated by a blinded committee., Results: For diuretic efficiency, there was no difference between dapagliflozin and usual care (OR: 0.65; 95% CI: 0.41-1.02; P = 0.06). Dapagliflozin was associated with reduced loop diuretic doses (560 mg [Q1-Q3: 260-1,150 mg] vs 800 mg [Q1-Q3: 380-1,715 mg]; P = 0.006) and fewer intravenous diuretic up-titrations (P ≤ 0.05) to achieve equivalent weight loss as usual care. Early dapagliflozin initiation did not increase diabetic, renal, or cardiovascular safety events. Dapagliflozin was associated with improved median 24-hour natriuresis (P = 0.03) and urine output (P = 0.005), expediting hospital discharge over the study period., Conclusions: Early dapagliflozin during AHF hospitalization is safe and fulfills a component of GDMT optimization. Dapagliflozin was not associated with a statistically significant reduction in weight-based diuretic efficiency but was associated with evidence for enhanced diuresis among patients with AHF. (Efficacy and Safety of Dapagliflozin in Acute Heart Failure [DICTATE-AHF]; NCT04298229)., Competing Interests: Funding Support and Author Disclosures This study was funded by AstraZeneca as an investigator-initiated study. The authors designed the protocol, conducted the trial according to the protocol and statistical analysis plan, analyzed the data, and attest to the accuracy and completeness of the data. The REDCap database is supported by a grant from National Center for Advancing Translational Sciences/National Institutes of Health (NIH) (UL1 TR000445). Dr Cox has received research funding from AstraZeneca; and has received consulting fees from Roche and Translational Catalyst. Dr Collins has performed consulting for Boehringer Ingelheim, Reprieve Cardiovascular, Siemens, and Abbott; and has received research support from the Patient-Centered Outcomes Research Institute, NIH, U.S. Department of Defense, Agency for Healthcare Research and Quality, and Beckman Coulter. Dr Lindsell has received funding from AstraZeneca, bioMerieux, Entegrion, Endpoint Health, NIH, the U.S. Department of Defense, and the Centers for Disease Control and Prevention. Dr Stubblefield has received funding from the NIH/National Heart, Lung, and Blood Institute. Dr Lindenfeld has received research funding from AstraZeneca, Volumetrix, and NIH; and has received consulting fees from AstraZeneca, Abbott, Alleviant, Axon, Boston Scientific, CVRx, Edwards Lifesciences, Medtronic, Merck, Vascular Dynamics, VWave, and Whiteswell. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

This scoping review aimed to determine whether the COVID-19 pandemic influenced any modifications to patient selection methods or prioritisation and services provided by proton therapy (PT) centres. This review was conducted based on the PRISMA methodology and Joanna Briggs Institute scoping review guidelines. A literature search was performed in Medline, Embase, Web of Science and Scopus, as well as grey literature. Keywords such as "COVID-19" and "Proton Therapy" were used. Articles published from 1 January 2020 in English were included. In total, 138 studies were identified of which 11 articles met the inclusion criteria. A scoping review design was chosen to capture the full extent of information published relating to the aim. Six of 11 articles included statements regarding treatment of COVID-19 patients. Three publications recommended deferred or alternative treatment, two indicated to treat urgent/emergency patients and one reported continuous treatment for infectious patients. Recurring impacts on PT provision included more frequent use of unconventional therapies, reduced referrals, delayed treatment starts and CT simulation, change in treatment target volumes and staffing limitations due to pandemic restrictions. Consequently, telehealth consults, remote work, reduction in patient visitors, screening procedures and rigorous cleaning protocols were recommended. Few publications detailed changes to patient selection or workflow methods during the pandemic. Further research is needed to obtain more detailed information regarding current global patient selection methods in PT, collecting this data could aid in future planning for PT in Australia., (© 2023 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.)

Purpose: Standard curative-intent chemoradiotherapy for human papillomavirus (HPV)-related oropharyngeal carcinoma results in significant toxicity. Since hypoxic tumors are radioresistant, we posited that the aerobic state of a tumor could identify patients eligible for de-escalation of chemoradiotherapy while maintaining treatment efficacy., Methods: We enrolled patients with HPV-related oropharyngeal carcinoma to receive de-escalated definitive chemoradiotherapy in a phase II study (ClinicalTrials.gov identifier: NCT03323463). Patients first underwent surgical removal of disease at their primary site, but not of gross disease in the neck. A baseline 18 F-fluoromisonidazole positron emission tomography scan was used to measure tumor hypoxia and was repeated 1-2 weeks intratreatment. Patients with nonhypoxic tumors received 30 Gy (3 weeks) with chemotherapy, whereas those with hypoxic tumors received standard chemoradiotherapy to 70 Gy (7 weeks). The primary objective was achieving a 2-year locoregional control (LRC) of 95% with a 7% noninferiority margin., Results: One hundred fifty-eight patients with T0-2/N1-N2c were enrolled, of which 152 patients were eligible for analyses. Of these, 128 patients met criteria for 30 Gy and 24 patients received 70 Gy. The 2-year LRC was 94.7% (95% CI, 89.8 to 97.7), meeting our primary objective. With a median follow-up time of 38.3 (range, 22.1-58.4) months, the 2-year progression-free survival (PFS) and overall survival (OS) rates were 94% and 100%, respectively, for the 30-Gy cohort. The 70-Gy cohort had similar 2-year PFS and OS rates at 96% and 96%, respectively. Acute grade 3-4 adverse events were more common in 70 Gy versus 30 Gy (58.3% v 32%; P = .02). Late grade 3-4 adverse events only occurred in the 70-Gy cohort, in which 4.5% complained of late dysphagia., Conclusion: Tumor hypoxia is a promising approach to direct dosing of curative-intent chemoradiotherapy for HPV-related carcinomas with preserved efficacy and substantially reduced toxicity that requires further investigation.

Background: There is a lack of literature of health-related quality of life endpoints for radial forearm (RF) versus anterolateral thigh (ALT) free flap reconstruction for glossectomy defects. Our goal was to perform a comprehensive evaluation of clinical, functional, and quality of life outcomes after glossectomy reconstruction using a RF or ALT flap., Methods: A retrospective review was performed on patients who underwent glossectomy and immediate reconstruction with RF or ALT flaps between 2016 and 2021. Outcomes of interest included readmission and reoperation rates, functional assessments, tracheostomy and gastrostomy tube status, and FACE-Q Head and Neck Cancer scores., Results: Seventy-eight patients consisting of 54 RF and 24 ALT free flaps were included. ALT patients had a larger median flap size (72 vs. 48 cm 2 , p = 0.021) and underwent mandibulotomy (50% vs. 7.4%, p < 0.0001) and base of tongue resection (58.3% vs. 24.1%, p = 0.005) at higher rates. No significant differences were found with respect to other outcomes., Conclusion: The RF and ALT flaps are suitable for glossectomy reconstruction, with minimal differences seen in postoperative outcomes. Our study suggests that ALT can be used in patients with base of tongue and larger defect sizes, while providing similar functional and clinical outcomes to RF reconstruction., (© 2023 Wiley Periodicals LLC.)

Competing Interests: Conflicts of interest The authors declare no conflicts of interest.

Abstract: Familial platelet disorder with associated myeloid malignancies (FPDMM) is caused by germline RUNX1 mutations and characterized by thrombocytopenia and increased risk of hematologic malignancies. We recently launched a longitudinal natural history study for patients with FPDMM. Among 27 families with research genomic data by the end of 2021, 26 different germline RUNX1 variants were detected. Besides missense mutations enriched in Runt homology domain and loss-of-function mutations distributed throughout the gene, splice-region mutations and large deletions were detected in 6 and 7 families, respectively. In 25 of 51 (49%) patients without hematologic malignancy, somatic mutations were detected in at least 1 of the clonal hematopoiesis of indeterminate potential (CHIP) genes or acute myeloid leukemia (AML) driver genes. BCOR was the most frequently mutated gene (in 9 patients), and multiple BCOR mutations were identified in 4 patients. Mutations in 6 other CHIP- or AML-driver genes (TET2, DNMT3A, KRAS, LRP1B, IDH1, and KMT2C) were also found in ≥2 patients without hematologic malignancy. Moreover, 3 unrelated patients (1 with myeloid malignancy) carried somatic mutations in NFE2, which regulates erythroid and megakaryocytic differentiation. Sequential sequencing data from 19 patients demonstrated dynamic changes of somatic mutations over time, and stable clones were more frequently found in older adult patients. In summary, there are diverse types of germline RUNX1 mutations and high frequency of somatic mutations related to clonal hematopoiesis in patients with FPDMM. Monitoring changes in somatic mutations and clinical manifestations prospectively may reveal mechanisms for malignant progression and inform clinical management. This trial was registered at www.clinicaltrials.gov as #NCT03854318., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Abstract: Deleterious germ line RUNX1 variants cause the autosomal dominant familial platelet disorder with associated myeloid malignancy (FPDMM), characterized by thrombocytopenia, platelet dysfunction, and a predisposition to hematologic malignancies (HMs). We launched a FPDMM natural history study and, from January 2019 to December 2021, enrolled 214 participants, including 111 patients with 39 different RUNX1 variants from 45 unrelated families. Seventy of 77 patients had thrombocytopenia, 18 of 18 had abnormal platelet aggregometry, 16 of 35 had decreased platelet dense granules, and 28 of 55 had abnormal bleeding scores. Nonmalignant bone marrows showed increased numbers of megakaryocytes in 12 of 55 patients, dysmegakaryopoiesis in 42 of 55, and reduced cellularity for age in 30 of 55 adult and 17 of 21 pediatric cases. Of 111 patients, 19 were diagnosed with HMs, including myelodysplastic syndrome, acute myeloid leukemia, chronic myelomonocytic leukemia, acute lymphoblastic leukemia, and smoldering myeloma. Of those 19, 18 were relapsed or refractory to upfront therapy and referred for stem cell transplantation. In addition, 28 of 45 families had at least 1 member with HM. Moreover, 42 of 45 patients had allergic symptoms, and 24 of 30 had gastrointestinal (GI) symptoms. Our results highlight the importance of a multidisciplinary approach, early malignancy detection, and wider awareness of inherited disorders. This actively accruing, longitudinal study will genotype and phenotype more patients with FPDMM, which may lead to a better understanding of the disease pathogenesis and clinical course, which may then inform preventive and therapeutic interventions. This trial was registered at www.clinicaltrials.gov as #NCT03854318.

Objective: To develop a protocol for the defatting of steatotic liver grafts during long-term ex situ normothermic machine perfusion., Background: Despite the alarming increase in donor organ shortage, the highly prevalent fatty liver grafts are often discarded due to the risk of primary nonfunction. Effective strategies preventing such outcomes are currently lacking. An exciting new avenue is the introduction of ex situ normothermic machine perfusion (NMP), enabling a liver to remain fully functional for up to 2 weeks and providing a unique window of opportunity for defatting before transplantation., Methods: Over a 5-year period, 23 discarded liver grafts and 28 partial livers from our resection program were tested during ex situ normothermic machine perfusion. The steatosis degree was determined on serial biopsies by expert pathologists, and triglyceride contents were measured simultaneously., Results: Of 51 liver grafts, 20 were steatotic, with up to 85% macrovesicular steatosis, and were perfused for up to 12 days. Ten livers displayed marked (5 of which almost complete) loss of fat, while the other 10 did not respond to long-term perfusion. Successful defatting was related to prolonged perfusion, automated glucose control, circadian nutrition, and L-carnitine/fenofibrate supplementation. Pseudopeliotic steatosis and the associated activation of Kupffer/stellate cells were unexpected processes that might contribute to defatting. Synthetic and metabolic functions remained preserved for most grafts until perfusion ended., Conclusion: Ex situ long-term perfusion effectively reduces steatosis while preserving organ viability and may in the future allow transplantation of primarily unusable high-risk grafts, significantly increasing the number of organs available for transplantation., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The purpose of this study is to report the clinical and radiologic outcomes of patients undergoing primary or revision reverse total shoulder arthroplasty using custom 3D-printed components to manage severe glenoid bone loss with a minimum of 2-year follow-up., Methods: Following ethical approval, patients were identified and invited to participate. Inclusion criteria were (1) severe glenoid bone loss necessitating the need for custom implants and (2) patients with definitive glenoid and humeral components implanted more than 2 years prior. Included patients underwent clinical assessment using the Oxford Shoulder Score (OSS), Constant-Murley score, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), and the quick Disabilities of the Arm, Shoulder, and Hand questionnaire (QuickDASH). Radiographic assessment included anteroposterior and axial projections. Patients were invited to attend a computed tomography (CT) scan to confirm osseointegration. Statistical analysis used descriptive statistics (mean and standard deviation [SD]) and paired t test for parametric data., Results: Eleven patients declined to participate. Five patients were deceased prior to study commencement, leaving 42 remaining patients in this analysis. Three patients had revision surgery before the 2-year follow-up; of these, 2 retained their custom glenoid components. Mean follow-up was 31.6 months from surgery (range 24-52 months). All 4 scores improved: OSS from a mean 15 (SD 8.4) to 36 (SD 12) (P < .001), Constant-Murley score from a mean 15 (SD 11.2) to 52 (SD 20.1) (P < .001), QuickDASH from a mean 70 (SD 21) to 31 (SD 24.8) (P = .004), and the ASES score from a mean 22 (SD 17.8) to 71 (SD 23.3) (P = .007). Radiologic evaluation demonstrated good osseointegration in all but 1 included patient., Conclusion: The utility of custom 3D-printed components for managing severe glenoid bone loss in primary and revision reverse total shoulder arthroplasty yields significant clinical improvements in this complex cohort. Large complex glenoid bone defects can be managed successfully with custom 3D-printed glenoid components., (Copyright © 2023 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Animal models have historically been poor preclinical predictors of gastrointestinal (GI) directed therapeutic efficacy and drug-induced GI toxicity. Human stem and primary cell-derived culture systems are a major focus of efforts to create biologically relevant models that enhance preclinical predictive value of intestinal efficacy and toxicity. The inherent variability in stem-cell-based complex cultures makes development of useful models a challenge; the stochastic nature of stem-cell differentiation interferes with the ability to build and validate robust, reproducible assays that query drug responses and pharmacokinetics. In this study, we aimed to characterize and reduce potential sources of variability in a complex stem cell-derived intestinal epithelium model, termed RepliGut ® Planar, across cells from multiple human donors, cell lots, and passage numbers. Assessment criteria included barrier formation and integrity, gene expression, and cytokine responses. Gene expression and culture metric analyses revealed that controlling for stem/progenitor-cell passage number reduces variability and maximizes physiological relevance of the model. After optimizing passage number, donor-specific differences in cytokine responses were observed in a case study, suggesting biologic variability is observable in cell cultures derived from multiple human sources. Our findings highlight key considerations for designing assays that can be applied to additional primary-cell derived systems, as well as establish utility of the RepliGut ® Planar platform for robust development of human-predictive drug-response assays., Competing Interests: Conflict of interest: CMP, BZ, MKB, BEM, MC, CB, JMM, JAL, DCG, RL, WT, MKB and EMB are current or previous employees of Altis Biosystems, Inc. DP, MBM, DM, RS are employees of Sciome.

Biomarkers are powerful clinical diagnostics and predictors of patient outcome. However, robust measurements often require time and expensive laboratory equipment, which is insufficient to track rapid changes and limits direct use in the operating room. Here, this study presents a portable spectrophotometric device for continuous real-time measurements of fluorescent and non-fluorescent biomarkers at the point of care. This study measures the mitochondrial damage biomarker flavin mononucleotide (FMN) in 26 extended criteria human liver grafts undergoing hypothermic oxygenated perfusion to guide clinical graft assessment. Real-time data identified seven organs unsuitable for transplant that are discarded. The remaining grafts are transplanted and FMN values correlated with post-transplant indicators of liver function and patient recovery. Further, this study shows how this device can be used to monitor dialysis patients by measuring creatinine in real-time. Our approach provides a simple method to monitor biomarkers directly within biological fluids to improve organ assessment, patient care, and biomarker discovery., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Objective: Little information exists about horse-related injury admissions to Level 1 trauma centers in the Western United States. This study describes injury patterns in this population, to reveal potential areas for injury prevention initiatives., Methods: A retrospective database review of 512 non-fatal equine-related injuries over a 15-year period was conducted, using a Level 1 hospital trauma registry. To determine patterns of injury, patients injured by riding or being near a horse were classified according to age, sex, helmet use, abbreviated injury score, anatomical region injured, and length of stay., Results: Equine-related injury was more frequent among females than males, the anatomical region most at risk among adults was the lower extremity (including pelvis), and among children and youth, the head. 75% of head-injured patients were not wearing a helmet at the time of injury and those with the most severe head injuries were least likely to be wearing a helmet., Conclusion: Preventable equine-related injuries occur across all ages, are more frequent among females, and affect all regions of the body. Despite head-injury risks associated with horse activities, helmet use was not common among most of the injured. Decreasing the risk of these injuries requires use of appropriate protective equipment and enhanced education campaigns aimed at those in the horse industry and the general public.

Malnutrition and food insecurity remain high in rural Rwanda, where residents consume a low-diversity diet provided through subsistence farming. Agricultural interventions using kitchen gardens may improve diet diversity in some populations. However, little is known about their efficacy when developed using community-based participatory research in combination with nutrition education focused on the empowerment of women. The objective of this study was to develop and implement a kitchen garden and nutrition education intervention using a community-engaged model and examine its impact on household diet diversity and food security. Using a mixed methods community-level design, we assessed a 16-week intervention implemented in Cyanika, Rwanda. Stratified purposeful sampling was used to select women participants representing 42 households. Household diet diversity scores (HHDS) and hunger scores were calculated at the baseline, post-intervention and one-year follow-up. HDDS increased after intervention from a pre-intervention intake of 2.59 [1.3] food groups/day, to 4.85 [1.6] at four months post-intervention and at one year post-intervention, reaching 5.55 [1.3]. There were no significant changes in household hunger scores. Our results indicate that collaborative community-engaged nutrition-sensitive agricultural interventions can increase household diet diversity; however, future work should explore whether this type of intervention strategy can lead to sustained changes and impact nutritional adequacy in this population.

Purpose: Perihaematomal oedema (PHO) formation has gained increasing interest as a therapeutic target after spontaneous intracerebral haemorrhage (ICH). Whether PHO contributes to poor outcome is unclear. We aimed to determine the association between PHO and outcome in patients with spontaneous ICH., Method: We searched five databases up to 17 November 2021 for studies of ⩾10 adults with ICH reporting the presence of PHO and outcome. We assessed risk of bias, extracted aggregate data and used random effects meta-analysis to pool studies that reported odds ratios (OR) with 95% confidence intervals (CI). Primary outcome was poor functional outcome defined as modified Rankin Scale score of 3-6 at 3 months. Additionally, we assessed PHO growth and poor outcome at any time of follow-up. We prospectively registered the protocol in PROSPERO (CRD42020157088)., Findings: We identified 12,968 articles, of which we included 27 studies ( n  = 9534). Eighteen studies reported an association between larger PHO volume and poor outcome, six a neutral result and three an inverse relationship. Larger absolute PHO volume was associated with poor functional outcome at 3 months (OR per mL increase of absolute PHO 1.03, 95% CI 1.00-1.06, I 2 44%, four studies). Additionally, PHO growth was associated with poor outcome (OR 1.04, 95% CI 1.02-1.06, I 2 0%, seven studies)., Discussion: In patients with spontaneous ICH, larger PHO volume is associated with poor functional outcome at 3 months. These findings support the development and investigation of new therapeutic interventions targeting PHO formation to evaluate if reduction of PHO improves outcome after ICH.

Background: Due to its affordability in disease-affected communities and suitability for field application, microscopy has historically been considered the gold standard for field diagnosis of trypanosomosis in rural settings., Aim: This works aims to compare the performance of microscopists on bovine trypanosome microscopy by organizing the first comparative assessment on a correct reading of slides by laboratory professionals using the read slide results and a structured interviewer-administered questionnaire in North-central Nigeria., Methods: Ten participants were addressed, as they were sent a panel of two slides (Slide 1: No Trypanosome present; Slide 2: Trypanosome present) and a questionnaire., Results: All participants greater than 41 years old reported correctly the presence and absence of parasites on slides. Only 3/8 of microscopists from routine diagnostic laboratories reported correctly the presence of the parasite., Conclusion: Our study confirmed errors in reading slides. Therefore, training of microscopists besides a nationwide quality assessment is recommended., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper.

The choice to postpone treatment while awaiting genetic testing can result in significant delay in definitive therapies in patients with severe pancytopenia. Conversely, the misdiagnosis of inherited bone marrow failure (BMF) can expose patients to ineffectual and expensive therapies, toxic transplant conditioning regimens, and inappropriate use of an affected family member as a stem cell donor. To predict the likelihood of patients having acquired or inherited BMF, we developed a 2-step data-driven machine-learning model using 25 clinical and laboratory variables typically recorded at the initial clinical encounter. For model development, patients were labeled as having acquired or inherited BMF depending on their genomic data. Data sets were unbiasedly clustered, and an ensemble model was trained with cases from the largest cluster of a training cohort (n = 359) and validated with an independent cohort (n = 127). Cluster A, the largest group, was mostly immune or inherited aplastic anemia, whereas cluster B comprised underrepresented BMF phenotypes and was not included in the next step of data modeling because of a small sample size. The ensemble cluster A-specific model was accurate (89%) to predict BMF etiology, correctly predicting inherited and likely immune BMF in 79% and 92% of cases, respectively. Our model represents a practical guide for BMF diagnosis and highlights the importance of clinical and laboratory variables in the initial evaluation, particularly telomere length. Our tool can be potentially used by general hematologists and health care providers not specialized in BMF, and in under-resourced centers, to prioritize patients for genetic testing or for expeditious treatment.

Patient education (PE) is vital in reducing anxiety, increasing satisfaction with treatment, helping with self-management, and creating a sense of control for cancer patients. Patients access much of their material from health care providers through in-person visits, patient libraries, and in-person classes. Due to reductions in in-person visits throughout the pandemic, we sought to understand how PE programs responded under varying levels of COVID-19 restrictions to meet the information needs of patients and families. A cross-sectional survey was distributed to members of the Cancer Patient Education Network (CPEN) and the Health Care Education Association (HCEA) via the respective listservs. The survey consisted of five sections that included closed and opened questions. Participants were asked questions to describe their PE programs and how their duties were affected during the pandemic. Forty-two CPEN members completed the survey (N = 42, 66%) with a 35% response rate and a 55% completion rate, and 19 HCEA members completed the survey (N = 19, 30%) with a 5% response rate and 16% completion rate. The majority of staff surveyed were not furloughed (N = 57/64, 89%). Just under half reported a change in daily PE program activities (N = 23/52, 44%) and most reported a change in developing PE materials (e.g., pamphlets) (N = 10/26, 63%), finding information for patients/families (N = 11/19, 58%), and delivering classes (N = 12/21, 57%). COVID-19 has ushered in a new era in the delivery of PE with the rapid deployment of digital cancer patient education. Results can inform future directions for the delivery of PE post-pandemic., (© 2022. The Author(s) under exclusive licence to American Association for Cancer Education.)

Objective: Examine the impact of Fuel for Fun: Cooking with Kids Plus Parents and Play (FFF) on children's culinary self-efficacy, attitude, fruit and vegetable (FV) preferences, physical activity (PA), and body mass index., Design: Randomized controlled trial., Setting: Eight elementary schools in 2 Northern Colorado districts., Participants: Fourth-grade students; 7-month interventions: school (S.FFF)-theory-based cooking + tasting lessons, active recess, lesson-driven cafeteria promotions; or school + family (S+F.FFF) with added family nights and home activities., Main Outcome Measure(s): Cooking self-efficacy and attitudes, FV preferences, PA, and measured height/weight., Analysis: Individual outcomes nested by classroom, school, and district and assessed > 12 months with repeated measures controlled by sex and baseline cooking experience, with a significance level of P < 0.05., Results: The sample included 1,428 youth, 38 teachers, 4 cohorts, 50% boys, 75% White, and 15% Hispanic. No intervention effect was observed. Those who cooked retained higher self-efficacy, attitude, and FV preferences (P < 0.001). Girls reported higher self-efficacy and attitude than boys. Moderate-to-vigorous PA and metabolic equivalent minutes increased for all students; boys retained higher levels (P < 0.001). Body mass index percentile remained stable., Conclusions and Implications: Cooking and sex were associated with all outcome measures and should be considered for intervention tailoring. Treatment impacts were not evident nesting by classroom, school, and district. Accurate assessment of school-based interventions requires rejecting student independence from group assignment assumptions., (Copyright © 2022 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)

A case report of a dentist presenting with allergic contact dermatitis to methacrylates present in dental bonding agent applied on the dorsum of a gloved hand. The patient presented with a localized dermatitis to the dorsum of the non-dominant hand which can be described as a 'manual tray sign'., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Diol scaffolds have been utilized as highly effective catalysts and ligands in a wide range of catalytic asymmetric transformations. For scaffolds to be successful as broadly used motifs, they should be prepared cheaply through facile routes and be easily handled. Herein, the synthesis of a family of planar chiral diols based on a modular and robust three-step route is described, which yields catalytically active diols in >99 % de and >99 % ee, with up to seven different chiral elements. These diols have been characterized by X-ray crystallographic analysis, which provides clear evidence for the likely transition state when applied in the asymmetric hetero-Diels-Alder reaction. Without altering the stereochemistry of the catalyst backbone, it is possible to access both enantiomers of the product by varying the substitution of the catalyst at the α-position., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Germline RUNX1 mutations lead to familial platelet disorder with associated myeloid malignancies (FPDMM), which is characterized by thrombocytopenia and a life-long risk (35-45%) of hematological malignancies. We recently launched a longitudinal natural history study for patients with FPDMM at the NIH Clinical Center. Among 29 families with research genomic data, 28 different germline RUNX1 variants were detected. Besides missense mutations enriched in Runt homology domain and loss-of-function mutations distributed throughout the gene, splice-region mutations and large deletions were detected in 6 and 7 families, respectively. In 24 of 54 (44.4%) non-malignant patients, somatic mutations were detected in at least one of the clonal hematopoiesis of indeterminate potential (CHIP) genes or acute myeloid leukemia (AML) driver genes. BCOR was the most frequently mutated gene (in 9 patients), and multiple BCOR mutations were identified in 4 patients. Mutations in 7 other CHIP or AML driver genes ( DNMT3A, TET2, NRAS, SETBP1, SF3B1, KMT2C , and LRP1B ) were also found in more than one non-malignant patient. Moreover, three unrelated patients (one with myeloid malignancy) carried somatic mutations in NFE2 , which regulates erythroid and megakaryocytic differentiation. Sequential sequencing data from 19 patients demonstrated dynamic changes of somatic mutations over time, and stable clones were more frequently found in elderly patients. In summary, there are diverse types of germline RUNX1 mutations and high frequency of somatic mutations related to clonal hematopoiesis in patients with FPDMM. Monitoring dynamic changes of somatic mutations prospectively will benefit patients’ clinical management and reveal mechanisms for progression to myeloid malignancies., Key Points: Comprehensive genomic profile of patients with FPDMM with germline RUNX1 mutations. Rising clonal hematopoiesis related secondary mutations that may lead to myeloid malignancies.

Objective: To describe the implementation and process characteristics of Fuel for Fun: Cooking with Kids Plus Parents and Play (FFF)., Design: Mixed methods., Setting: Elementary schools in 2 Northern Colorado school districts., Participants: Fourth graders (aged 9-11 years), parents, school staff, and implementation researchers; measured over 2 consecutive years in 8 schools (851 students, 45 classrooms)., Intervention(s): Social Cognitive and active learning theory-based classroom cooking with tasting lessons, active recess games, cooking with tasting food promotion during school lunch, family nights, and take-home intervention reinforcements. A 7-month program delivered by a trained intervention team., Main Outcome Measure(s): Implementation measures (observations and debriefings) assessed context, reach, dose delivered, fidelity, and dose received; process measures (surveys) assessed student and parent perceptions and intervention participation., Analysis: Descriptive statistics for quantitative and themes for qualitative data., Results: Minor adjustments in program delivery plans were required to accommodate changes in school schedules and policies. Process measures demonstrated > 90% achievement of goals for nearly all child-centered activities. One-quarter of eligible families participated in evening events, with strong parent and student approval. Fifty out of 116 parents (43%) completing an online survey reported preparing ≥ 1 of 5 recipes with their child. Fifty-nine percent of eligible students completed >1 of 10 take-home activity sheets with their parents., Conclusions and Implications: Engagement and commitment of the intervention team and school staff supported strong implementation. Participant responses were positive, but improvement in parent engagement requires investigation., (Copyright © 2022 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)

This report describes the development and revision of core competencies for the Expanded Food and Nutrition Education Program and Supplemental Nutrition Assistance Program-Education program leaders, supervisors, and paraprofessional educators across the land-grant university system. The developing curriculum methodologies were used to engage panels of exemplary employees and an advisory panel of program leaders. A crosswalk examined key documents, and a gap analysis explored the competencies of similar professions. The resulting job duties and tasks reflect cultural, environmental, and educational trends. The core competencies are critical for writing job descriptions, guiding hiring, evaluating performance, and providing initial and ongoing training for the Expanded Food and Nutrition Education Program and Supplemental Nutrition Assistance Program-Education., (Copyright © 2022. Published by Elsevier Inc.)

We report a general, catalyst-controlled route to prostaglandin F2 α and its analogues. The approach uses a Rh-catalyzed dynamic kinetic asymmetric Suzuki-Miyaura coupling reaction between a racemic bicyclic allyl chloride and alkenyl boronic esters bearing chiral alcohols to give cyclopentyl intermediates bearing 3 contiguous stereocenters. The route provides advanced intermediates in 99% ee as a single diastereoisomer in all cases examined, with the absolute stereochemistry of the cyclopentane core controlled by the ligand. Intermediates that could be used to produce prostaglandin analogues such as bimatoprost, latanoprost, fluprostenol, and cloprostenol were synthesized. The final two stereocenters were installed via Pd-catalyzed Tsuji-Trost alkylation and iodolactonization. The synthesis of PG F2 α was achieved in 19% yield in 16 longest linear steps.

Csp 2 -Csp 2 Suzuki-Miyaura couplings (SMCs) are ubiquitous in the synthesis of small molecules, but analogous Csp 2 -Csp 3 bond-forming SMCs are rare, especially asymmetric variants. Recently, we developed a series of Rh-catalyzed couplings between racemic sp 3 -hybridized allyl chlorides and heteroaryl boronic acids. Here, we demonstrate that these catalytic asymmetric reactions can be scaled-up to give over 100 g of a product. The reaction we chose to test couples a heteroaromatic boronic acid derivative and a racemic bicyclic electrophile to give a product with three contiguous stereogenic centers. The SMC product was obtained as a single diastereomer in 90% yield and 98% ee. Kinetic analysis of the reaction reveals two exothermic steps in the reaction setup and revealed the means by which to prevent the generation of heat spikes detrimental to the stability of the catalyst., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Introduction: Although executive functioning (EF) correlates with execution of instrumental activities of daily living (IADLs), tests of EF have been criticized for having poor ecological validity. Attempts have been made to develop new tests that approximate naturalistic daily tasks. However, the incremental utility of such tests has not been convincingly demonstrated. The Night Out Task (NOT) is a novel measure designed to increase ecological validity. This study examined whether the NOT correlates with traditional lab- and home-based measures of EF and IADLs, and whether it outperforms traditional measures of EF in predicting IADLs., Method: Participants (50 adults aged 60 to 95) completed (1) the Delis Kaplan Executive Function System (D-KEFS) and IADLs in the laboratory, and (2) ecological momentary assessment of EF and daily IADL tasks at home across three weeks (using the Daily Assessment of Independent Living and Executive Skills protocol; DAILIES)., Results: The NOT correlated with a lab-based measure of EF beyond covariates, and lab-based IADLs beyond covariates and beyond the D-KEFS. However, it was unrelated to at-home variables beyond covariates. In contrast, the D-KEFS was a significant predictor of at-home IADLs, and this association was mediated by at-home EF performance., Conclusion: This study provides a preliminary validation of the NOT as a correlate of office-based performances in a primarily college educated white sample. Despite its high face validity, the NOT does not appear to sufficiently tap EF processes needed for home-based IADLs as measured by the DAILIES, although small sample size limits the interpretability of this negative finding.

Introduction: Policy, systems, and environmental (PSE) change approaches frequently address healthy eating and active living (HEAL) priorities. However, the health effects of PSE HEAL initiatives are not well known because of their design complexity and short duration. Planning and evaluation frameworks can guide PSE activities to generate collective impact. We applied a systematic mapping review to the Individual plus PSE Conceptual Framework for Action (I+PSE) to describe characteristics, achievements, challenges, and evaluation strategies of PSE HEAL initiatives., Methods: We identified peer-reviewed articles published from January 2009 through January 2021 by using CINAHL, Web of Science, MEDLINE, PsycINFO, and CAB Abstracts databases. Articles describing implementation and results of PSE HEAL initiatives were included. Activities were mapped against I+PSE components to identify gaps in evaluation efforts., Results: Independent reviewers examined 437 titles and abstracts; 52 peer-reviewed articles met all inclusion criteria. Twenty-four focused on healthy eating, 5 on active living, and 23 on HEAL. Descriptive analyses identified federal funding of initiatives (typically 1-3 years), multisector settings, and mixed-methods evaluation strategies as dominant characteristics. Only 11 articles reported on initiatives that used a formal planning and evaluation framework. Achievements focused on partnership development, individual behavior, environmental or policy changes, and provision of technical assistance. Challenges included lack of local coalition and community engagement in initiatives and evaluation activities and insufficient time and resources to accomplish objectives. The review team noted vague or absent descriptions of evaluation activities, resulting in questionable characterizations of processes and outcomes. Although formation of partnerships was the most commonly reported accomplishment, I+PSE mapping revealed a lack of engagement assessment and its contributions toward initiative impact., Conclusion: PSE HEAL initiatives reported successes in multiple areas but also challenges related to partnership engagement and community buy-in. These 2 areas are essential for the success of PSE HEAL initiatives and need to be adequately evaluated so improvements can be made.

The freshwater snail genus Bulinus plays a vital role in transmitting parasites of the Schistosoma haematobium group. A hybrid schistosome between S. haematobium and S. mattheei has been recently detected using DNA-based identification methods in school children along the Lake Malawi shoreline in Mangochi District. This finding raised the need for contemporary revaluation of local interactions between schistosomes and snails, with a particular focus on snail species within the Bulinus africanus group. In 2017 and 2018, malacological surveys sampled several freshwater sites in Mangochi District. Collected snails ( n = 250) were characterised using cytochrome oxidase subunit 1 gene ( cox 1), with DNA barcoding of the 'Folmer' region and a rapid PCR-RFLP typing assay with double digestion with Hae III and Sac I restriction enzymes. DNA cox 1 sequence analysis, with phylogenetic tree construction, suggested the presence of at least three B. africanus group taxa in Lake Malawi, B. globosus, alongside first reports of B. africanus and B. angolensis, which can be differentiated by PCR-RFLP methods. In addition, a total of 30 of the 106 B. africanus group snails (28.30%) were positive to the Schistosoma -specific screen using real-time PCR methods. This study provides new insight into the recent changes in the epidemiology of urogenital schistosomiasis as likely driven by a new diversity of B. africanus group snails within the Lake.

We report on a search for compact binary coalescences where at least one binary component has a mass between 0.2  M&#95;{⊙} and 1.0  M&#95;{⊙} in Advanced LIGO and Advanced Virgo data collected between 1 April 2019 1500 UTC and 1 October 2019 1500 UTC. We extend our previous analyses in two main ways: we include data from the Virgo detector and we allow for more unequal mass systems, with mass ratio q≥0.1. We do not report any gravitational-wave candidates. The most significant trigger has a false alarm rate of 0.14  yr^{-1}. This implies an upper limit on the merger rate of subsolar binaries in the range [220-24200]  Gpc^{-3} yr^{-1}, depending on the chirp mass of the binary. We use this upper limit to derive astrophysical constraints on two phenomenological models that could produce subsolar-mass compact objects. One is an isotropic distribution of equal-mass primordial black holes. Using this model, we find that the fraction of dark matter in primordial black holes in the mass range 0.2  M&#95;{⊙}

Introduction: Childhood obesity disproportionately affects low-income women, children, racial/ethnic minorities, and rural populations. To effectively promote sustainable change, healthy eating and active living initiatives should apply individual plus policy, systems, and environmental (I + PSE) approaches., Methods: Four public health maternal and child nutrition teams selected through an application process participated in 12 months of technical assistance (TA) to develop action plans incorporating I + PSE in nutrition programming. TA included: (1) online modules; (2) community of practice (CoP) meetings; and (3) individual coaching sessions. Teams completed midpoint and endpoint surveys to assess TA knowledge and process outcomes. Semi-structured, in-depth interviews conducted post TA were transcribed and content analysis used to characterize themes and sub-themes., Results: Facilitators to implementing I + PSE approaches included TA delivery through online modules, participation in the CoP, and individual coaching to address barriers to implementation and leadership support. Barriers were time and funding limitations, working in isolation, and lack of infrastructure and self-efficacy. Co-learning helped TA teams overcome stagnancy and promote development of creative solutions. Teams recognized relationship-building as integral to systems development., Discussion: Lessons learned occurred across three main areas: relationships, capacity-building, and barriers encountered. Relationship formation takes time and is often not recognized as an asset impacting public health programing. Relationship direction - upstream, downstream, and lateral - affects ability to build organizational and systems capacity. While this study includes a small number of public health nutrition teams, this practice-based research highlights the value of I + PSE TA to tackle complex problems, with reciprocal, multisectoral support to enhance public health nutrition program impact., (© 2022. The Author(s).)

Background: Tsetse flies (Glossina) transmit Trypanosoma brucei gambiense which causes Gambian human African trypanosomiasis (gHAT) in Central and West Africa. Several countries use Tiny Targets, comprising insecticide-treated panels of material which attract and kill tsetse, as part of their national programmes to eliminate gHAT. We studied how the scale and arrangement of target deployment affected the efficacy of control., Methodology and Principal Findings: Between 2012 and 2016, Tiny Targets were deployed biannually along the larger rivers of Arua, Maracha, Koboko and Yumbe districts in North West Uganda with the aim of reducing the abundance of tsetse to interrupt transmission. The extent of these deployments increased from ~250 km2 in 2012 to ~1600 km2 in 2015. The impact of Tiny Targets on tsetse populations was assessed by analysing catches of tsetse from a network of monitoring traps; sub-samples of captured tsetse were dissected to estimate their age and infection status. In addition, the condition of 780 targets (~195/district) was assessed for up to six months after deployment. In each district, mean daily catches of tsetse (G. fuscipes fuscipes) from monitoring traps declined significantly by >80% following the deployment of targets. The reduction was apparent for several kilometres on adjacent lengths of the same river but not in other rivers a kilometre or so away. Expansion of the operational area did not always produce higher levels of suppression or detectable change in the age structure or infection rates of the population, perhaps due to the failure to treat the smaller streams and/or invasion from adjacent untreated areas. The median effective life of a Tiny Target was 61 (41.8-80.2, 95% CI) days., Conclusions: Scaling-up of tsetse control reduced the population of tsetse by >80% across the intervention area. Even better control might be achievable by tackling invasion of flies from infested areas within and outside the current intervention area. This might involve deploying more targets, especially along smaller rivers, and extending the effective life of Tiny Targets., Competing Interests: The authors have declared that no competing interests exist.

Myostatin (MSTN), also known as growth differentiation factor 8 (GDF-8), is a negative regulator of lean muscle tissue growth. Variation in the gene has been studied in many domesticated species, because of its potential to dramatically increase muscle mass. It has, however, not been investigated in red deer ( Cervus elaphus ). In this study, variation in MSTN intron 1 was investigated in 211 male New Zealand red deer, for which phenotypic measurements of M. Longissimus dorsi (eye muscle) (width, depth, and area, together with 12-month weight) were recorded. Two sequence variants (named A and B ) differing by one nucleotide (c.373 + 224) were identified in the intron 1 region of the gene resulting in three genotypes ( AA , AB, and BB ; frequencies of 63.5%, 30.8%, and 5.7%, respectively), but no association between this variation and any of the quantitative measurements was detected. These results suggest that the deer MSTN is less variable than for other livestock species and that its activity may be controlled to maintain a size-growth equilibrium.

Background: Contact allergy is a major clinical and public health challenge. It is important to identify individuals who are at risk and perform patch testing to identify relevant allergens. Predicting clinical risk on the basis of input parameters is common in clinical medicine and traditionally has been achieved with linear models., Objectives: We hypothesized that the risk of a clinically relevant positive patch test could be predicted according to clinical and demographic parameters., Methods: We compared the predictive accuracy of logistic regression with more sophisticated machine learning approaches such as gradient boosting, in the prediction of patch testing results., Results: We found that both logistic regression and more sophisticated machine learning approaches were able to predict the risk of positive patch tests. For certain predictions, including the overall risk of a clinically relevant positive patch test, gradient boosting approaches can outperform logistic regression., Conclusions: These findings suggest that complex nonlinear interactions between input variables are relevant in risk prediction. While a risk prediction model cannot replace the judgment of an experienced clinician, quantifying the risk of a clinically relevant positive patch test result has the potential to assist in decision making and to inform discussions with patients., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

During COVID-19 infection, reduced function of natural killer (NK) cells can lead to both compromised viral clearance and dysregulation of the immune response. Such dysregulation leads to overproduction of cytokines, a raised neutrophil/lymphocyte ratio and monocytosis. This in turn increases IL-6 expression, which promotes scar and thrombus formation. Excess IL-6 also leads to a further reduction in NK function through downregulation of perforin expression, therefore forming a pathogenic auto-inflammatory feedback loop. The perforin/granzyme system of cytotoxicity is the main mechanism through which NK cells and cytotoxic T lymphocytes eliminate virally infected host cells, as well as being central to their role in regulating immune responses to microbial infection. Here, we present epidemiological evidence suggesting an association between perforin expression and resistance to COVID-19. In addition, we outline the manner in which a pathogenic auto-inflammatory feedback loop could operate and the relationship of this loop to genes associated with severe COVID-19. Such an auto-inflammatory loop may be amenable to synergistic multimodal therapy., (© 2021 The Scandinavian Foundation for Immunology.)

Background: Parent participation in children's health interventions is insufficiently defined and measured. This project quantified parent participation to enable future examination with outcomes in an intervention focused on 4th graders, aged 9-11 years, and their families living in northern Colorado., Methods: Indices were developed to measure type (Parent Participation Profile; PPP) and intensity (Parent Engagement Intensity; PEI) of engagement in Fuel for Fun (FFF), an asymmetric school-and family-based intervention for 4th graders. Study arm-specific participation opportunities were catalogued and summed to calculate the PPP. An algorithm considered frequency, effort, convenience, and invasiveness of each activity to calculate PEI. Indices were standardized (0-100%) using study arm-specific divisors to address asymmetric engagement opportunities. Parents who completed ≥75% of the PPP were defined as Positive Deviants. Youth height and weight were measured. Youth BMI percentile change was compared with parent Positive Deviant status using general linear modeling with repeated measures that included the participation indices., Results: Of 1435 youth, 777 (54%) had parent participation in at least one activity. Standardized means were 41.5 ± 25.4% for PPP and 27.6 ± 20.9% for PEI. Demographics, behaviors or baseline FFF outcomes did not differ between the Positive Deviant parent (n = 105) and non-Positive Deviant parents (n = 672); but more Positive Deviant parents followed an indulgent feeding style (p = 0.015). Standardized intensity was greater for Positive Deviant parents; 66.9 ± 20.6% vs 21.5 ± 12.7% (p < 0.001) and differences with non-Positive Deviant parents were related to activity type (p ≤0.01 for six of eight activities). Standardized participation intensity was associated with engagement in a greater number of standardized activity types. Among participating parents, standardized intensity and breadth of activity were inversely related to the youth BMI percentile (n = 739; PEI r = -0.39, p < 0.001; PPP r = -0.34, p < 0.001). Parent engagement was not associated with parent BMI change., Conclusions: An activity-specific intensity schema operationalized measurement of parent engagement in a complex, unbalanced research design and can serve as a template for more sensitive assessment of parent engagement. Positive deviance in parent engagement was not a function of personal, but rather activity characteristics. PPP and PEI increased with fewer requirements and convenient, novel, and personalized activities. Parent engagement indices affirmed lower engagement by parents of overweight/obese youth and concerns about target reach., (© 2021. The Author(s).)