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Background: This study used Community Partnered Participatory Research (CPPR) to address low participation of racial and ethnic minorities in medical research and the lack of trust between underrepresented communities and researchers. Methods: Using a community and academic partnership in July 2012, residents of a South Los Angeles neighborhood were exposed to research recruitment strategies: referral by word-of-mouth, community agencies, direct marketing, and extant study participants. Results: Among 258 community members exposed to recruitment strategies, 79.8% completed the study. Exposed individuals identified their most important method for learning about the study as referral by study participants (39.8%), community agencies (30.6%), word-of-mouth (17.5%), or direct marketing promotion (12.1%). Study completion rates varied by recruitment method: referral by community agencies (88.7%), referral by participants (80.4%), direct marketing promotion (86.2%), word of mouth (64.3%). Conclusions: Although African American and Latino communities are often described as difficult to engage in research, we found high levels of research participation and completion when recruitment strategies emerged from the community itself. This suggests recruitment strategies based on CPPR principles represent an important opportunity for addressing health disparities and our high rates of research completion should provide optimism and a road map for next steps.

Kimberly Fairbrother,1 Ben Cartner,1 Jessica R Alley,1 Chelsea D Curry,1, David L Dickinson,2 David M Morris,1 Scott R Collier1 1Vascular Biology and Autonomic Studies Laboratory, Department of Health and Exercise Science, 2Department of Economics, Appalachian State University, Boone, NC, USA Background: During nocturnal sleep, blood pressure (BP) “dips” compared to diurnal BP, reducing stress on the cardiovascular system. Both the hypotensive response elicited by acute aerobic exercise and sleep quality can impact this dipping response. Purpose: The purpose of this study was to investigate the effects of aerobic exercise timing on circadian BP changes and sleep architecture. Materials and methods: Twenty prehypertensive subjects completed the study. During four test sessions, participants first completed a graded exercise test to exhaustion and then performed 30 minutes of treadmill exercise at 7 am (7A), 1 pm (1P), and 7 pm (7P) in a random, counterbalanced order at 65% of the heart rate obtained at peak oxygen uptake. An ambulatory cuff was used to monitor BP responses during 24 hours following exercise, and an ambulatory sleep-monitoring headband was worn during sleep following each session. Results: Aerobic exercise at 7A invoked a greater dip in nocturnal systolic BP than exercise at 1P or 7P, although the greatest dip in nocturnal diastolic BP occurred following 7P. Compared to 1P, 7A also invoked greater time spent in deep sleep. Conclusion: These data indicate that early morning may be the most beneficial time to engage in aerobic exercise to enhance nocturnal BP changes and quality of sleep. Keywords: nocturnal dipping, prehypertension, aerobic exercise

Objective: Magnetic resonance imaging allows the noninvasive observation of PO2 changes between air breathing and oxygen breathing through quantification of the magnetic longitudinal relaxation time T1. Changes in PO2 are proportional to changes in the longitudinal relaxation rate ΔR1 (where ΔR1=1/T1oxygen-1/T1air). Knowledge of this response could inform clinical interventions using maternal oxygen administration antenatally to treat fetal growth restriction. We present in vivo measurements of the response of the fetal-placental unit to maternal hyperoxia.Design: Prospective cohort.Setting: Large tertiary maternity hospital.Sample: Nine women undergoing low-risk pregnancy (21-33 weeks of gestation) and five nonpregnant adults.Methods: During imaging the air supply to mothers was changed from medical air (21% oxygen) to medical oxygen (100% oxygen) and T1 was monitored over time in both the placenta and fetal brain using a periodically repeated magnetic resonance imaging sequence. To demonstrate that the method could detect a brain response, brain responses from five normal adult volunteers were measured using a similar imaging protocol.Main Outcome Measure: Changes in T1 following oxygen challenge.Results: No significant ΔR1 (P=0.42, paired t-test) was observed in fetal brains. A significant placental ΔR1 (P=0.0002, paired t-test) of 0.02±0.01/s (mean±SD) was simultaneously observed in the same participants. In the brains of the nonpregnant adults, a significant ΔR1 (P=0.01, paired t-test) of 0.005±0.002/s was observed.Conclusion: Short-term maternal oxygen administration does not improve fetal brain oxygenation, in contrast to the response observed in the adult brain. [ABSTRACT FROM AUTHOR]

Objective Magnetic resonance imaging allows the noninvasive observation of Po2 changes between air breathing and oxygen breathing through quantification of the magnetic longitudinal relaxation time T1. Changes in Po2 are proportional to changes in the longitudinal relaxation rate Δ R1 (where Δ R1 = 1/ T1oxygen − 1/ T1air). Knowledge of this response could inform clinical interventions using maternal oxygen administration antenatally to treat fetal growth restriction. We present in vivo measurements of the response of the fetal-placental unit to maternal hyperoxia. Design Prospective cohort. Setting Large tertiary maternity hospital. Sample Nine women undergoing low-risk pregnancy (21-33 weeks of gestation) and five nonpregnant adults. Methods During imaging the air supply to mothers was changed from medical air (21% oxygen) to medical oxygen (100% oxygen) and T1 was monitored over time in both the placenta and fetal brain using a periodically repeated magnetic resonance imaging sequence. To demonstrate that the method could detect a brain response, brain responses from five normal adult volunteers were measured using a similar imaging protocol. Main outcome measure Changes in T1 following oxygen challenge. Results No significant Δ R1 ( P = 0.42, paired t-test) was observed in fetal brains. A significant placental Δ R1 ( P = 0.0002, paired t-test) of 0.02 ± 0.01/s (mean ± SD) was simultaneously observed in the same participants. In the brains of the nonpregnant adults, a significant Δ R1 ( P = 0.01, paired t-test) of 0.005 ± 0.002/s was observed. Conclusion Short-term maternal oxygen administration does not improve fetal brain oxygenation, in contrast to the response observed in the adult brain. [ABSTRACT FROM AUTHOR]

Balance dysfunction and falls-related injuries represent serious public health issues, resulting in great expense and human suffering. The physical problems leading to balance dysfunction include musculoskeletal-related structural limitations, diminished sensory capabilities, motor coordination deficits, and loss of anticipatory control mechanisms. The water has been described as an effective environment for addressing balance dysfunction through both rehabilitation and fitness activities. This article describes the underlying physical problems leading to balance dysfunction, provides a rationale for using aquatic therapy to positively influence balance control, and presents evidence to support the use of aquatic therapy for the management of balance dysfunction. [ABSTRACT FROM AUTHOR]

The great prevalence of traumatic brain injury (TBI) and its high economic costs make reducing TBI-related disability a national health care priority. In our research laboratory, CI therapy has been found to significantly improve upper extremity function for persons with chronic TBI. The results have suggested that persons with TBI are less likely to adhere to critical components of the CI therapy protocol than participants with stroke in other studies. Treatment outcomes have also been more variable. Our findings suggest that some cognitive skills appear related to treatment outcome. In addition, cognitive and behavioral deficits, commonly seen with participants with TBI, challenge the delivery of the standard CI therapy protocol with some persons. We discuss the implications of these neuropsychological factors for CI therapy used for chronic TBI and propose further research to more thoroughly investigate these issues. [ABSTRACT FROM AUTHOR]

Constraint-Induced Movement therapy (CI therapy) is a recognized rehabilitation approach for persons having stroke with mild to moderately severe motor upper extremity deficits. To date, no rehabilitation treatment protocol has been proven effective that addresses both motor performance and spontaneous upper extremity use in the life situation for chronic stroke participants having severe upper extremity impairment with no active finger extension or thumb abduction. This case report describes treatment of a chronic stroke participant with a plegic hand using a CI therapy protocol that combines CI therapy with selected occupational and physical therapy techniques. Treatment consisted of six sessions of adaptive equipment and upper extremity orthotics training followed by a three-week, six-hour daily intervention of CI therapy plus neurodevelopmental treatment. Outcome measures included the Motor Activity Log for very low functioning patients (Grade 5 MAL), upper extremity portion of the Fugl-Meyer Motor Assessment, Graded Wolf Motor Function Test - for very low functioning patients (gWMFT- Grade 5), and Modified Ashworth Scale. The participant showed improvement on each outcome measure with the largest improvement on the Grade 5 MAL. In follow-up, the participant had good retention of his gains in motor performance and use of his more affected arm for real world activities after 3 months; after a one-week brush-up at 3 months, and at one year post-treatment. [ABSTRACT FROM AUTHOR]

Bone marrow adipose tissue is a distinct adipose subtype comprising more than 10% of fat mass in healthy humans. However, the functions and pathophysiological correlates of this tissue are unclear, and its genetic determinants remain unknown. Here, we use deep learning to measure bone marrow adiposity in the femoral head, total hip, femoral diaphysis, and spine from MRI scans of approximately 47,000 UK Biobank participants, including over 41,000 white and over 6300 non-white participants. We then establish the heritability and genome-wide significant associations for bone marrow adiposity at each site. Our meta-GWAS in the white population finds 67, 147, 134, and 174 independent significant single nucleotide polymorphisms, which map to 54, 90, 43, and 100 genes for the femoral head, total hip, femoral diaphysis, and spine, respectively. Transcriptome-wide association studies, colocalization analyses, and sex-stratified meta-GWASes in the white participants further resolve functional and sex-specific genes associated with bone marrow adiposity at each site. Finally, we perform a multi-ancestry meta-GWAS to identify genes associated with bone marrow adiposity across the different bone regions and across ancestry groups. Our findings provide insights into BMAT formation and function and provide a basis to study the impact of BMAT on human health and disease., Competing Interests: Competing interests: G.P. is currently an employee of Pfizer; however, Pfizer had no role in the design or interpretation of this research. All other authors declare no competing interests., (© 2024. The Author(s).)

Background: T 2 mapping is valuable to evaluate pathophysiology in kidney disease. However, variations in T 2 relaxation time measurements across MR scanners and vendors may occur requiring additional correction., Purpose: To harmonize renal T 2 measurements between MR vendor platforms, and use an extended-phase-graph-based fitting method ("StimFit") to correct stimulated echoes and reduce between-vendor variations., Study Type: Prospective., Subjects: 8 healthy "travelling" volunteers (37.5% female, 32 ± 6 years) imaged on four MRI systems across three vendors at four sites, 10 healthy volunteers (50% female, 32 ± 8 years) scanned multiple times on a given MR scanner for repeatability evaluation. ISMRM/NIST system phantom scanned for evaluation of T 2 accuracy., Field Strength/sequence: 3T, multiecho spin-echo sequence., Assessment: T 2 images fit using conventional monoexponential fitting and "StimFit." Mean absolute percentage error (MAPE) of phantom measurements with reference T 2 values. Average cortex and medulla T 2 values compared between MR vendors, with masks obtained from T 2 -weighted images and T 1 maps. Full-width-at-half-maximum (FWHM) T 2 distributions to evaluate local homogeneity of measurements., Statistical Tests: Coefficient of variation (CV), linear mixed-effects model, analysis of variance, student's t-tests, Bland-Altman plots, P-value <0.05 considered statistically significant., Results: In the ISMRM/NIST phantom, "StimFit" reduced the MAPE from 4.9%, 9.1%, 24.4%, and 18.1% for the four sites (three vendors) to 3.3%, 3.0%, 6.6%, and 4.1%, respectively. In vivo, there was a significant difference in kidney T 2 measurements between vendors using a monoexponential fit, but not with "StimFit" (P = 0.86 and 0.92, cortex and medulla, respectively). The intervendor CVs of T 2 measures were reduced from 8.0% to 2.6% (cortex) and 7.1% to 2.8% (medulla) with StimFit, resulting in no significant differences for the CVs of intravendor repeat acquisitions (P = 0.13 and 0.05). "StimFit" significantly reduced the FWHM of T 2 distributions in the cortex and whole kidney., Data Conclusion: Stimulated-echo correction reduces renal T 2 variation across MR vendor platforms., Level of Evidence: 2 TECHNICAL EFFICACY: Stage 1., (© 2024 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Study Design: Mixed-method approach., Objectives: To develop and assess the content validity of a semi-structured interview that captures the lived experience of using a manual wheelchair among individuals with SCI in the real world, the Wheelchair Mobility Activity Log (WC-MAL)., Setting: SCIR-Group (UDESC)/Brazil., Methods: Developing the WC-MAL comprised five steps: (1) defining the construct-based on the International Classification of Functioning, Disability and Health (ICF); (2) identifying relevant activities from other assessment instruments and interviews with the end-users (14 Individuals with SCI and 13 rehabilitation professionals); (3) Selecting the items - activities were linked to ICF codes and grouped into sets; (4) developing the scoring scales based on interviews with the end-users; and, (5) evaluating content validity in accordance with the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). The content validity ratio (CVR) for each item and scale and the overall instrument content validity index (CVI) were calculated., Results: From an initial draft of 295 activities identified, a set of 222 activities was linked to the ICF domain of "Mobility (d4)" and further refined to generate the 23 items in the WC-MAL. Three scales were developed to assess Frequency (how often), Performance (how well), and Assistance (assistance needed) levels. The items and scales showed a CVR superior to the critical value established (≥0.64). The general CVI value was 0.96., Conclusion: The WC-MAL is a promising clinical instrument with adequate content validity to assess the spontaneous use of the manual wheelchair in the real world among individuals with SCI., (© 2024. The Author(s), under exclusive licence to International Spinal Cord Society.)

Background: Bone marrow adipose tissue (BMAT) represents > 10% fat mass in healthy humans and can be measured by magnetic resonance imaging (MRI) as the bone marrow fat fraction (BMFF). Human MRI studies have identified several diseases associated with BMFF but have been relatively small scale. Population-scale studies therefore have huge potential to reveal BMAT's true clinical relevance. The UK Biobank (UKBB) is undertaking MRI of 100,000 participants, providing the ideal opportunity for such advances., Objective: To establish deep learning for high-throughput multi-site BMFF analysis from UKBB MRI data., Materials and Methods: We studied males and females aged 60-69. Bone marrow (BM) segmentation was automated using a new lightweight attention-based 3D U-Net convolutional neural network that improved segmentation of small structures from large volumetric data. Using manual segmentations from 61-64 subjects, the models were trained to segment four BM regions of interest: the spine (thoracic and lumbar vertebrae), femoral head, total hip and femoral diaphysis. Models were tested using a further 10-12 datasets per region and validated using datasets from 729 UKBB participants. BMFF was then quantified and pathophysiological characteristics assessed, including site- and sex-dependent differences and the relationships with age, BMI, bone mineral density, peripheral adiposity, and osteoporosis., Results: Model accuracy matched or exceeded that for conventional U-Nets, yielding Dice scores of 91.2% (spine), 94.5% (femoral head), 91.2% (total hip) and 86.6% (femoral diaphysis). One case of severe scoliosis prevented segmentation of the spine, while one case of Non-Hodgkin Lymphoma prevented segmentation of the spine, femoral head and total hip because of T2 signal depletion; however, successful segmentation was not disrupted by any other pathophysiological variables. The resulting BMFF measurements confirmed expected relationships between BMFF and age, sex and bone density, and identified new site- and sex-specific characteristics., Conclusions: We have established a new deep learning method for accurate segmentation of small structures from large volumetric data, allowing high-throughput multi-site BMFF measurement in the UKBB. Our findings reveal new pathophysiological insights, highlighting the potential of BMFF as a novel clinical biomarker. Applying our method across the full UKBB cohort will help to reveal the impact of BMAT on human health and disease., Competing Interests: G.P. is currently an employee of Pfizer; however, Pfizer had no role in the design or interpretation of this research. All other authors declare no competing interest., (© 2024 The Authors.)

Background: The COVID-19 pandemic is suspected to have affected cancer care and outcomes among patients in Canada. In this study, we evaluated the impact of the state of emergency period during the COVID-19 pandemic (Mar. 17 to June 15, 2020) on cancer diagnoses, stage at diagnosis and 1-year survival in Alberta., Methods: We included new diagnoses of the 10 most prevalent cancer types from Jan. 1, 2018, to Dec. 31, 2020. We followed patients up to Dec. 31, 2021. We used interrupted time series analysis to examine the impact of the first COVID-19-related state of emergency in Alberta on the number of cancer diagnoses. We used multivariable Cox regression to compare 1-year survival of the patients who received a diagnosis during 2020 after the state of emergency with those who received a diagnosis during 2018 and 2019. We also performed stage-specific analyses., Results: We observed significant reductions in diagnoses of breast cancer (incidence rate ratio [IRR] 0.67, 95% confidence interval [CI] 0.59-0.76), prostate cancer (IRR 0.64, 95% CI 0.56-0.73) and colorectal cancer (IRR 0.64, 95% CI 0.56- 0.74) and melanoma (IRR 0.57, 95% CI 0.47-0.69) during the state of emergency period compared with the period before it. These decreases largely occurred among early-stage rather than late-stage diagnoses. Patients who received a diagnosis of colorectal cancer, non-Hodgkin lymphoma and uterine cancer in 2020 had lower 1-year survival than those diagnosed in 2018; no other cancer sites had lower survival., Interpretation: The results from our analyses suggest that health care disruptions during the COVID-19 pandemic in Alberta considerably affected cancer outcomes. Given that the largest impact was observed among early-stage cancers and those with organized screening programs, additional system capacity may be needed to mitigate future impact., Competing Interests: Competing interests: Daniel Heng reports receiving consulting fees from Bristol Myers Squibb, Merck, Ipsen, Exelixis, Novartis, Pfizer and Eisai. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

The study of self-control occurs in many different types of experimental settings using a wide range of methodologies. In addition, measures of self-control vary in their procedures and operational definitions from simple questionnaires to complex scenarios where individuals must choose to act or not. The present summary draws on trends within the literature using widely accepted measures of self-control. The measures are organized based on established paradigms in the literature and focus on three categories: executive functioning tasks, delay of gratification tasks, and subjective-report surveys. We also include an "additional measures" category to capture measures that do not readily fit in these three categories. Finally, we discuss recent approaches to the scientific exploration of self-control and integrate the categories of measures used here within these approaches. This integration incorporates a wide range of research paradigms and provides direction for future studies.

Objectives The purpose of the current study was to examine the effects of using an activity workstation on the physiological stress response as measured by heart rate variability while completing cognitively demanding tasks. Participants: Eleven college students (6 females; age: 19.4 ± 0.9 years) participated in the study. Methods: The participants completed three psychologically stressful cognitive tasks while seated at a traditional desk and while using an activity workstation. Heart rate variability was recorded and analyzed with power spectrum density and time-domain analysis. Results: Using activity workstations while completing stressful cognitive tasks did not negatively affect task performance. There was; however, a reduction in low frequency heart rate variability but no change in cardiac sympathovagal balance. Conclusion: The results indicate that using activity workstations while completing difficult tasks reduces sympathetic reactivity to stress in college students. This suggests that using activity workstations could provide a coping mechanism for stress.

There is an increasing focus on health promotion in physical therapist research and practice. A clinical model (Health-Focused Physical Therapy Model) was developed for identifying major steps in the delivery of health promotion focusing on adoption of healthy lifestyle behaviors. One of the primary steps within this model is the design and delivery of behavior change interventions. Such interventions involve coordinated sets of activities that target change in a specific pattern of unhealthy behavior (eg, physical inactivity, smoking). This Perspective contends that the science and practice of behavior change interventions can be significantly advanced in the field of physical therapy (implementation science) through the integration of behavior change frameworks and techniques within the context of an experimental medicine approach for health behavior change. This perspective presents the integration of the Theoretical Domains Framework, the Behavior Change Wheel, including the Capability Opportunity Motivation-Behavior core system, and the Behavior Change Technique Taxonomy as a comprehensive approach for designing and delivering behavior change interventions in physical therapy. An experimental medicine approach is described, outlining a 4-step process in the design, delivery, and evaluation of behavior change interventions that can be applied to health promotion in physical therapist research and practice. The proposed integrative approach can advance public health and health promotion through healthy lifestyle behavior change in the field of physical therapy., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Kawasaki-like multisystem inflammatory syndrome related to SARS-CoV-2 infection is a well-described condition in children and adolescents (MIS-C) and now also in adults (MIS-A). We report a case of MIS-A in a previously well woman in her mid-30s who presented with vasopressor-dependent shock 2 weeks after initial recovery from suspected SARS-CoV-2 infection, accompanied by fever, vomiting, diarrhoea, weakness, arthralgia, rash, cough and headache. Examination was notable for fever, tachycardia, hypotension, cervical lymphadenopathy, mucocutaneous involvement, neck stiffness, pansystolic murmur and bilateral crepitations. Inflammatory markers were elevated. Echocardiogram showed mitral regurgitation with preserved ejection fraction. She was treated with vasopressors, admitted to the intensive care unit and subsequently required invasive mechanical ventilation. Both PCR and antibodies for SARS-CoV-2 were positive. Treatment with intravenous methylprednisolone and intravenous immunoglobulin was initiated with rapid improvement in clinical condition and inflammatory markers. She has since made a full recovery with normal echocardiogram 8 months later., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Phase-contrast (PC) MRI is a feasible and valid noninvasive technique to measure renal artery blood flow, showing potential to support diagnosis and monitoring of renal diseases. However, the variability in measured renal blood flow values across studies is large, most likely due to differences in PC-MRI acquisition and processing. Standardized acquisition and processing protocols are therefore needed to minimize this variability and maximize the potential of renal PC-MRI as a clinically useful tool., Purpose: To build technical recommendations for the acquisition, processing, and analysis of renal 2D PC-MRI data in human subjects to promote standardization of renal blood flow measurements and facilitate the comparability of results across scanners and in multicenter clinical studies., Study Type: Systematic consensus process using a modified Delphi method., Population: Not applicable., Sequence Field/strength: Renal fast gradient echo-based 2D PC-MRI., Assessment: An international panel of 27 experts from Europe, the USA, Australia, and Japan with 6 (interquartile range 4-10) years of experience in 2D PC-MRI formulated consensus statements on renal 2D PC-MRI in two rounds of surveys. Starting from a recently published systematic review article, literature-based and data-driven statements regarding patient preparation, hardware, acquisition protocol, analysis steps, and data reporting were formulated., Statistical Tests: Consensus was defined as ≥75% unanimity in response, and a clear preference was defined as 60-74% agreement among the experts., Results: Among 60 statements, 57 (95%) achieved consensus after the second-round survey, while the remaining three showed a clear preference. Consensus statements resulted in specific recommendations for subject preparation, 2D renal PC-MRI data acquisition, processing, and reporting., Data Conclusion: These recommendations might promote a widespread adoption of renal PC-MRI, and may help foster the set-up of multicenter studies aimed at defining reference values and building larger and more definitive evidence, and will facilitate clinical translation of PC-MRI., Level of Evidence: 1 TECHNICAL EFFICACY STAGE: 1., (© 2020 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC. on behalf of International Society for Magnetic Resonance in Medicine.)

Introduction: Liver cirrhosis is a growing global healthcare challenge. Cirrhosis is characterised by severe liver fibrosis, organ dysfunction and complications related to portal hypertension. There are no licensed antifibrotic or proregenerative medicines and liver transplantation is a scarce resource. Hepatic macrophages can promote both liver fibrogenesis and fibrosis regression. The safety and feasibility of peripheral infusion of ex vivo matured autologous monocyte-derived macrophages in patients with compensated cirrhosis has been demonstrated., Methods and Analysis: The efficacy of autologous macrophage therapy, compared with standard medical care, will be investigated in a cohort of adult patients with compensated cirrhosis in a multicentre, open-label, parallel-group, phase 2, randomised controlled trial. The primary outcome is the change in Model for End-Stage Liver Disease score at 90 days. The trial will provide the first high-quality examination of the efficacy of autologous macrophage therapy in improving liver function, non-invasive fibrosis markers and other clinical outcomes in patients with compensated cirrhosis., Ethics and Dissemination: The trial will be conducted according to the ethical principles of the Declaration of Helsinki 2013 and has been approved by Scotland A Research Ethics Committee (reference 15/SS/0121), National Health Service Lothian Research and Development department and the Medicine and Health Care Regulatory Agency-UK. Final results will be presented in peer-reviewed journals and at relevant conferences., Trial Registration Numbers: ISRCTN10368050 and EudraCT; reference 2015-000963-15., Competing Interests: Competing interests: PNB has received honoraria from Takeda. JAF has received consultancy fees for Ferring Pharmaceuticals, Macrophage Pharma, Aquilla BioMedical, Caldan Therapeutics, Cypralis, Third Rock Ventures, Rallybio, Narrow River Management, Gilde Healthcare, Guidepoint, Techspert.io and acted as advisory board member for: Novartis, Galecto Biotech, Tectonic Therapeutic and received research grant funding from Novartis and Intercept Pharmaceuticals. JFD has received honoraria and research grants from Gilead, AbbVie and MSD. JDMC and SJF are founders and scientific advisers to Resolution Therapeutics., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To determine the test-retest reliability and validity of the Lower Extremity Motor Activity Log (LE-MAL) for assessing LE use in the community in adults with multiple sclerosis (MS)., Design: Prospective analysis of measures conducted by trained examiners., Setting: Participants were evaluated by telephone on several measures of LE use., Participants: Adults with MS (N=43)., Interventions: Not applicable., Main Outcome Measures: The LE-MAL has 3 subscales (Assistance, Functional Performance, and Confidence). It was administered twice, at least 2 weeks apart. The Multiple Sclerosis Walking Scale (MSWS-12), Patient Determined Disease Steps (PDDS), and Mobility Scale were only administered during the first call., Results: The test-retest reliability of the composite and the 3 subscale LE-MAL scores were high (intraclass correlation, >0.94). The composite and subscale LE-MAL scores were strongly correlated with the MSWS-12, PDDS, and Mobility Scale scores (r=-0.56 to -0.77; P<.001)., Conclusion: This initial study suggests that the LE-MAL reliably and validly measures LE use in the community in adults with MS., (Copyright © 2020 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

The worldwide spread of the novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a global pandemic since its identification in Wuhan, China in December 2019. 1 Few cases of COVID-19-associated dermatologic manifestations have been reported in the literature to date. This report describes the clinical features of a localized pruritic scarlatiniform rash of the ears and antecubital fossa on defervescence in a 29-year-old patient with COVID-19. Our case stands to further illuminate the dermatologic manifestations of this novel disease., Competing Interests: Conflict of interest: The authors declare that there are no conflicting or competing interests., (© Copyright 2021 by the American Board of Family Medicine.)

Background: Although Constraint-Induced Movement therapy (CIMT) has been deemed efficacious for adults with persistent, mild-to-moderate, post-stroke upper-extremity hemiparesis, CIMT is not available on a widespread clinical basis. Impediments include its cost and travel to multiple therapy appointments. To overcome these barriers, we developed an automated, tele-health form of CIMT., Objective: Determine whether in-home, tele-health CIMT has outcomes as good as in-clinic, face-to-face CIMT in adults ≥1-year post-stroke with mild-to-moderate upper-extremity hemiparesis., Methods: Twenty-four stroke patients with chronic upper-arm extremity hemiparesis were randomly assigned to tele-health CIMT (Tele-AutoCITE) or in-lab CIMT. All received 35 hours of treatment. In the tele-health group, an automated, upper-extremity workstation with built-in sensors and video cameras was set-up in participants' homes. Internet-based audio-visual and data links permitted supervision of treatment by a trainer in the lab., Results: Ten patients in each group completed treatment. All twenty, on average, showed very large improvements immediately afterwards in everyday use of the more-affected arm (mean change on Motor Activity Log Arm Use scale = 2.5 points, p < 0.001, d' = 3.1). After one-year, a large improvement from baseline was still present (mean change = 1.8, p < 0.001, d' = 2). Post-treatment outcomes in the tele-health group were not inferior to those in the in-lab group. Neither were participants' perceptions of satisfaction with and difficulty of the interventions. Although everyday arm use was similar in the two groups after one-year (mean difference = -0.1, 95% CI = -1.3-1.0), reductions in the precision of the estimates of this parameter due to drop-out over follow-up did not permit ruling out that the tele-health group had an inferior long-term outcome., Conclusions: This proof-of-concept study suggests that Tele-AutoCITE produces immediate benefits that are equivalent to those after in-lab CIMT in stroke survivors with chronic upper-arm extremity hemiparesis. Cost savings possible with this tele-health approach remain to be evaluated.

APOE4 is a major risk factor for sporadic Alzheimer's disease; however, it is unclear how it exerts its pathological effects. Others and we have previously shown that autophagy is impaired in APOE4 compared to APOE3 astrocytes, and demonstrated differences in the expression of mitochondrial dynamics proteins in brains of APOE3 and APOE4 transgenic mice. Here, we investigated the effect of APOE4 expression on several aspects of mitochondrial function and network dynamics, including fusion, fission, and mitophagy, specifically in astrocytes. We found that APOE3 and APOE4 astrocytes differ in their mitochondrial dynamics, suggesting that the mitochondria of APOE4 astrocytes exhibit reduced fission and mitophagy. APOE4 astrocytes also show impaired mitochondrial function. Importantly, the autophagy inducer rapamycin enhanced mitophagy and improved mitochondrial functioning in APOE4 astrocytes. Collectively, the results demonstrate that APOE4 expression is associated with altered mitochondrial dynamics, which might lead to impaired mitochondrial function in astrocytes. This, in turn, may contribute to the pathological effects of APOE4 in Alzheimer's disease.

A 56-yr-old woman with chronic stroke and gait dysfunction was recruited for this study. A lower-extremity constraint-induced movement therapy protocol was given consisting of 3.5 hrs/d of supervised intervention activities on 10 consecutive weekdays. Motor training was intensive and involved shaping. In addition, a group of behavior management strategies was used to induce further unsupervised practice and transference of motor skills from the laboratory to real-world situations. Changes in functional mobility, walking speed, balance, level of assistance, perceived quality of movement, and level of confidence while performing daily activities were assessed five times in both the baseline and intervention phases. The outcomes observed after the intervention were determined by calculating the difference between the average scores obtained in both phases. Changes in perceived quality of movement, level of confidence, level of assistance, and balance were observed.

To develop technical recommendations on the acquisition and post-processing of renal longitudinal (T1) and transverse (T2) relaxation time mapping. A multidisciplinary panel consisting of 18 experts in the field of renal T1 and T2 mapping participated in a consensus project, which was initiated by the European Cooperation in Science and Technology Action PARENCHIMA CA16103. Consensus recommendations were formulated using a two-step modified Delphi method. The first survey consisted of 56 items on T1 mapping, of which 4 reached the pre-defined consensus threshold of 75% or higher. The second survey was expanded to include both T1 and T2 mapping, and consisted of 54 items of which 32 reached consensus. Recommendations based were formulated on hardware, patient preparation, acquisition, analysis and reporting. Consensus-based technical recommendations for renal T1 and T2 mapping were formulated. However, there was considerable lack of consensus for renal T1 and particularly renal T2 mapping, to some extent surprising considering the long history of relaxometry in MRI, highlighting key knowledge gaps that require further work. This paper should be regarded as a first step in a long-term evidence-based iterative process towards ever increasing harmonization of scan protocols across sites, to ultimately facilitate clinical implementation.

The interaction between sleep and work-related behaviors influence many aspects of employee performance, safety, and health as well as organizational-level success. Although it is well established that quantity and quality of sleep can affect different types of task performance and personal health, the interactions between sleep habits and organizational behaviors have received much less attention. It is important to examine how sleep habits and workplace behaviors relate and the role of the underlying circadian rhythm on the potential impact of sleep and sleepiness in the workplace. Developing a deeper understanding of how sleep habits and sleepiness impact workers and the organization can help provide the necessary background for human resource management to develop more progressive support networks for employees that benefit both the worker and the organization. Human resources and employees should emphasize the impact of good sleep and sleep habits on organizational and individual productivity and safety., (Copyright © 2020 Pilcher and Morris.)

Introduction: Gastrointestinal upset is a common presentation to surgical departments, often requiring investigation with endoscopy. Pathologies such as gastritis or ulcers are common culprits. Occasionally, rare or unusual pathologies, such as gastric diverticula as was seen in the case presented, are found., Case Presentation: A 26 year old female, with no known co-morbid conditions presented with a two week history of abdominal pain associated with nausea and vomiting. On further inquiry, she had one episode of blood stained vomiting, prompting investigation with an oesophagogastroduodenoscopy (OGD). Findings included diffuse haemorrhagic gastritis with a single outpouching measuring 1-2 cm in the gastric fundus. A gastric diverticulum was confirmed on barium swallow. Investigation with sonar and a Computed Tomography (CT) scan reported the stomach as normal., Conclusion: The patient was successfully treated non-operatively with proton pump inhibitor therapy for her concomitant gastritis. Gastric Diverticula are often associated with other gastric findings and their individual contribution varies from case to case., Discussion: Gastric Diverticula are the manifestation of a common condition in an unusual location. Their clinical implications vary from being insignificant to life threatening when complicated by haemorrhage, perforation or malignant transformation. The associated symptoms are non-specific and diagnosis may be challenging. The case highlights the importance of selecting appropriate imaging modalities for luminal structures, being only diagnosed in 2 (OGD, Swallow) of the four modalities (incl. ultrasound and CT scan) used. Treatment may be conservative or surgical and is patient dependent. Written consent and ethical approval was obtained. The work is reported in line with the SCARE criteria., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Removal of chloride from Cp*Ir(glycinato)Cl in noncoordinating solvents with Ag[PF 6 ] or Tl[PF 6 ] leads to the formation of a closed octametallic loop of cations. The same loop also sequesters a number of PF 6 - counter anions. This is in contrast with reports that piano-stool complexes with amino acids form only trimetallic [Cp*Ir(aminoacidato)] 3 3+ moieties upon creating the cation. Cp*Ir(glycinato)Cl also forms a trimetallic compound as well as a octametallic compound, and the octametallic vs trimetallic formation appears to be dependent on the anion. The synthesis and characterization of the octametallic complex, as well as some monometallic and trimetallic compounds, are reported, including the X-ray crystal structures., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

Terrestrial arthropod fauna have been suggested as a key indicator of ecological integrity in forest systems. Because phenotypic identification is expert-limited, a shift towards DNA metabarcoding could improve scalability and democratize the use of forest floor arthropods for biomonitoring applications. The objective of this study was to establish the level of field sampling and DNA extraction replication needed for arthropod biodiversity assessments from soil. Processing 15 individually collected soil samples recovered significantly higher median richness (488-614 sequence variants) than pooling the same number of samples (165-191 sequence variants) prior to DNA extraction, and we found no significant richness differences when using 1 or 3 pooled DNA extractions. Beta diversity was robust to changes in methodological regimes. Though our ability to identify taxa to species rank was limited, we were able to use arthropod COI metabarcodes from forest soil to assess richness, distinguish among sites, and recover site indicators based on unnamed exact sequence variants. Our results highlight the need to continue DNA barcoding local taxa during COI metabarcoding studies to help build reference databases. All together, these sampling considerations support the use of soil arthropod COI metabarcoding as a scalable method for biomonitoring.

We present a case of a 23-year-old woman with dysphagia. She was reportedly newly diagnosed with HIV and had been initiated on antiretroviral treatment and tuberculosis (TB) prophylaxis. Oesophagogastroduodenoscopy revealed an irregular, ulcerative oesophageal lesion. Subsequent histopathology revealed M ycobacterium tuberculosis as well as C andida albicans A CT scan demonstrated widespread disease with miliary TB. She was subsequently initiated on antituberculous and antifungal medications. TB is one of the most common and deadly infectious diseases in the world, with the highest rates seen in the developing countries. It commonly occurs as an opportunistic infection of HIV. Despite its potential for systemic infection, infection of the oesophagus is incredibly rare, more so as a co-infection with candida. This case highlights the need to have a high index of suspicion in high risk groups, as early treatment is crucial in addressing this global health crisis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Constraint-induced movement therapy (CI therapy) has been shown to reduce disability for individuals with upper extremity (UE) hemiparesis following different neurologic injuries. This article describes the study design and methodological considerations of the Bringing Rehabilitation to American Veterans Everywhere (BRAVE) Project, a randomized controlled trial of CI therapy to improve the motor deficit of participants with chronic and subacute traumatic brain injury. Our CI therapy protocol comprises 4 major components: (1) intensive training of the more-affected UE for target of 3 hour/day for 10 consecutive weekdays, (2) a behavioral technique termed shaping during training, (3) a "transfer package," 0.5 hour/day, of behavioral techniques to transfer therapeutic gains from the treatment setting to the life situation, and (4) prolonged restraint of use of the UE not being trained. The primary endpoint is posttreatment change on the Motor Activity Log, which assesses the use of the more-affected arm outside the laboratory in everyday life situations. Data from a number of secondary outcome measures are also being collected and can be categorized as physical, genomic, biologic, fitness, cognitive/behavioral, quality of life, and neuroimaging measures.

A series of high-performance cycloparaffinic fuels have been generated by [2+2] cycloaddition of the bio-derived alkenes 1-hexene, isoprene, and 1-pentene, catalyzed by a low-valent iron pyridine(diimine) complex [( Me PDI)Fe(N 2 ) 2 (μ-N 2 )] [ Me PDI=N,N'-(2,6-pyridinediyldiethylidyne)bis(2,6-dimethylbenzenamine)]. Reactions with 1-pentene and 1-hexene resulted in 85 % selectivity to 1,2-cyclobutanes, and 12 % selectivity to acyclic alkenes generated by β-hydride elimination. Self-dimerization of isoprene was sluggish and generated heavier oligomer products, but cross-dimerization of isoprene with 1-hexene afforded primarily a 1,3-cyclobutane product, along with isomers of acyclic C 11 mixed dimers. Hydrocarbon mixtures were hydrogenated and fractionally distilled to yield finished fuel mixtures in overall yields of 83-93 % at the multigram scale. The fuels exhibited densities ranging between 0.767 and 0.783 g mL -1 , and net heats of combustion (NHOC) of up to 120.6 kBtu gal -1 (43.8 MJ kg -1 ). These values are higher than conventional synthetic paraffinic kerosenes owing to the higher density and ring strain afforded by the cyclobutane rings. The fuel mixtures also exhibited extremely low viscosities ranging from 2.38 to 4.78 mm 2  s -1 at -20 °C, due in part to the presence of the acyclic dimers. The excellent fuel properties of the product mixtures, selectivity for dimer products, high yields, and the ability to use simple bio-derived alkenes as substrates, make the [Fe]-catalyzed [2+2] cycloaddition of unactivated alkenes a compelling route to the synthesis of sustainable high-performance fuels., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

ADC is a potential post treatment imaging biomarker in colorectal liver metastasis however measurements are affected by respiratory motion. This is compounded by increased statistical uncertainty in ADC measurement with decreasing tumour volume. In this prospective study we applied a retrospective motion correction method to improve the image quality of 15 tumour data sets from 11 patients. We compared repeatability of ADC measurements corrected for motion artefact against non-motion corrected acquisition of the same data set. We then applied an error model that estimated the uncertainty in ADC repeatability measurements therefore taking into consideration tumour volume. Test-retest differences in ADC for each tumour, was scaled to their estimated measurement uncertainty, and 95% confidence limits were calculated, with a null hypothesis that there is no difference between the model distribution and the data. An early post treatment scan (within 7 days of starting treatment) was acquired for 12 tumours from 8 patients. When accounting for both motion artefact and statistical uncertainty due to tumour volumes, the threshold for detecting significant post treatment changes for an individual tumour in this data set, reduced from 30.3% to 1.7% (95% limits of agreement). Applying these constraints, a significant change in ADC (5 th and 20 th percentiles of the ADC histogram) was observed in 5 patients post treatment. For smaller studies, motion correcting data for small tumour volumes increased statistical efficiency to detect post treatment changes in ADC. Lower percentiles may be more sensitive than mean ADC for colorectal metastases.

Carboxysomes are closed polyhedral cellular microcompartments that increase the efficiency of carbon fixation in autotrophic bacteria. Carboxysome shells consist of small proteins that form hexameric units with semipermeable central pores containing binding sites for anions. This feature is thought to selectively allow access to RuBisCO enzymes inside the carboxysome by HCO 3 - (the dominant form of CO 2 in the aqueous solution at pH 7.4) but not O 2 , which leads to a nonproductive reaction. To test this hypothesis, here we use molecular dynamics simulations to characterize the energetics and permeability of CO 2 , O 2 , and HCO 3 - through the central pores of two different shell proteins, namely, CsoS1A of α-carboxysome and CcmK4 of β-carboxysome shells. We find that the central pores are in fact selectively permeable to anions such as HCO 3 - , as predicted by the model.