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Abstract Background Given the high prevalence of neck pain, the neck disability index (NDI) has been used to evaluate patient status and treatment outcomes. Modified versions were proposed as solutions to measurement deficits in the NDI. However, the original 10-item NDI was scored out of 50 and is still the most frequently administered version. Examining the extent of agreement between traditional and Rasch-based versions using Bland-Altman (B&A) plots will inform our understanding of score differences that might rise from using different versions. Therefore, the objective of current study was to describe the extent of agreement between different versions of NDI. Methods The current study was a secondary data analysis. The study data was compiled from two prospectively collected data sources. We performed a comprehensive literature search to identify Rasch approved NDI within four databases including Embase, Medline, PubMed, and Google Scholar. Alternate forms and scorings were compared to each other and to the standard NDI. We graphed B&A plots and calculated the mean difference and the 95% limits of agreement (LoA; ±1.96 times the standard deviation). Results Two Rasch approved alternative versions (8 vs 5 items) were identified from 303 screened publications. We analyzed data from 201 (43 males and 158 females) patients attending community clinics for neck pain. We found that the mean difference was approximately 10% of the total score between the 10-item and 5-item (− 4.6 points), whereas the 10-item versus 8-item and 8-item versus 5-item had smaller mean differences (− 2.3 points). The B&A plots displayed wider 95% LoA for the agreement between 10-item and 8-item (LoA: − 12.0, 7.4) and 5-item (LoA: − 14.9, 5.8) compared with the LoA for the 8-item and 5-item (LoA: − 7.8, 3.3). Conclusion Two Rasch-based NDI solutions (8 vs 5 items) which differ in number of items and conceptual construction are available to provide interval level scoring. They both provide scores that are substantially different from the ordinal NDI, which does not provide interval level scoring. Smaller differences between the two Rasch solutions exist and may relate to the items included. Due to the size and unpredictable nature of the bias between measures, they should not be used interchangeably.

Abstract Background The Pain Catastrophizing Scale (PCS) is a widely used self-report tool to evaluate pain related catastrophizing. The PCS was developed using classical test theory and has been shown to be psychometrically sound among various populations. However, it’s current three subscales are rarely used in clinical practice, offering potential for an abbreviated version that reduces administrative burden and can be used to estimate full scale scores, yet is not bound by the inclusion of items from each subscale. Hence, the aim of the current study was to develop a unidimensional abbreviated version of the PCS through findings from qualitative, classical test theory, and newer Rasch analysis. Methods The current cross-sectional study used data from the Quebec Pain Registry (n = 5646) to obtain PCS scores of people seeking care at tertiary chronic pain centres. To develop an abbreviated unidimensional tool, items were removed based on triangulation of qualitative review of each item and response, corrected item-total correlations, and Rasch analysis. Confirmatory factor analysis was conducted on the final remaining items to confirm the tool was assessing a single latent construct (catastrophizing). Fit was assessed using the cumulative fit index (CFI), Tucker Lewis Index (TLI), and root-mean-squared error of approximation (RMSEA). Results After triangulation, a final abbreviated 4-item scale showed adequate model fit with a strong correlation (r > 0.95) with the original scale and properties that were stable across age, sex, cause, and medicolegal status. Additionally, the brief version addressed some problematic wording on some items on the original scale. Both the original and new abbreviated tool were associated with the Beck Depression Inventory and the Brief Pain Inventory at the same magnitude. Conclusion The abbreviated scale may allow for a decrease in administrator burden and greater clinical uptake when a quick screen for exaggerated negative orientation towards pain is needed.

Abstract Background Total shoulder arthroplasty (TSA) is considered as the standard reconstructive surgery for patients suffering from severe shoulder pain and dysfunction caused by arthrosis. Multiple patient-reported outcome measures (PROMs) have been developed and validated that can be used to evaluate TSA outcomes. When selecting an outcome measure both content and psychometric properties must be considered. Most research to date has focused on psychometric properties. Therefore, the current study aims to summarize what PROMs are being used to assess TSA outcomes, to classify the type of measure (International society for quality of life (ISOQOL) using definitions of functioning, disability, and health (FDH), quality of life (QoL) and health-related quality of life (HRQoL)) and to compare the content of these measures by linking them to the International Classification of Functioning, Disability and Health (ICF) framework. Methods A literature review was performed in three databases including MEDLINE, EMBASE, and CINAHL to identify PROMs that were used in TSA studies. Meaningful concepts of the identified measures were extracted and linked to the relevant second-level ICF codes using standard linking rules. Outcome measures were classified as being FDH, HRQoL or QoL measures based on the content analysis. Result Thirty-five measures were identified across 400 retrieved studies. The most frequently used PROM was the American Shoulder and Elbow Society score accounting for 21% (246) of the total citations, followed by the single item pain-related scale like visual analog scale (17%) and Simple Shoulder Test (12%). Twelve PROMs with 190 individual items fit inclusion criteria for conceptual analysis. Most codes (65%) fell under activity and participation categories. The top 3 most predominant codes were: sensation of pain (b280; 13%), hand and arm use (d445; 13%), recreational activity (d920; 8%). Ten PROMs included in this study were categorized as FDH measures, one as HRQoL measure, and one as unknown. Conclusions Our study demonstrated that there is an inconsistency and lack of clarity in conceptual frameworks of identified PROMs. Despite this, common core constructs are evaluated. Decision-making about individual studies or core sets for outcome measurement for TSA would be advanced by considering our results, patient priorities and measurement properties.

Abstract Background Fluid resuscitation has become the cornerstone of early septic shock management, but the optimal fluid rate is still not well studied. The goal of this investigation is to examine the relationship between fluid resuscitation rate and septic shock resolution. Method We retrospectively studied adult (≥ 18 years) patients with septic shock, defined based on sepsis III definition, from January 1, 2006, through May 31, 2018, in the medical intensive care unit (MICU) of Mayo Clinic Rochester. The fluid resuscitation time was defined as the time required to infuse the initial fluid bolus of 30 ml/kg, based on the recommendations of the 2016 surviving sepsis campaign. The cohort was divided into four groups based on the average fluid rate (group 1 ≥ 0.5, group 2 0.25–0.49, group 3 0.17–0.24, and group 4

Background: Recently, a shorter version of the Western Ontario Rotator Cuff Index (Short-WORC) was created to reduce patient response burden. However, it has yet to be evaluated prospectively for reproducibility (reliability and agreement) and floor and ceiling effects. Methods: Patients (N = 162) with rotator cuff disorders completed the Short-WORC at baseline. From this cohort, 47 patients underwent measurement of test-retest reliability within 2 to 7 days. We used the Cronbach α to determine internal consistency and the intraclass correlation coefficient (ICC2,1) to assess test-retest reliability. To evaluate parameters of agreement, the standard error of measurement, minimal detectable change (based on a 90% confidence interval), and Bland-Altman plots were used. Results: The Cronbach α was 0.82 at baseline, and the intraclass correlation coefficient (ICC2,1) was 0.87. The agreement parameter was 8.4 for the standard error of measurement of agreement, and the limits of agreement fell within the range of –22.9 to 23.8. The Short-WORC is reliable over time and reflective of a patient’s true score after an intervention. Conclusions: The Short-WORC demonstrated strong reproducibility parameters and can be used for patients with rotator cuff disorders. The Short-WORC indicated no systematic bias and was reflective of the true score of both individual patients and groups of patients at 2 time points.

Abstract Background The shortened version of the Western Ontario Rotator Cuff Index (Short-WORC) is a patient reported outcome measure that evaluates quality of life (QoL) of patients with rotator cuff pathology. However, formal content validation of the full or Short-WORC has not been reported. This study aims to understand how 1) people interpret and calibrate responses to items on the Short-WORC and 2) compensatory strategies that might enhance function and thereby affect responses. Methods This study uses cognitive interviewing, a qualitative methodology that focuses on the interpretation of questionnaire items. Patients with rotator cuff disorders (n = 10), clinicians (n = 6) and measurement researchers (n = 10) were interviewed using a talk aloud structured interview that evaluated each of the 7 items of the Short-WORC. All interviews were recorded and transcribed verbatim by one researcher (R.F). Analysis was done through an open coding scheme using a previously established framework. Results Overall, the items on the Short-WORC were well received by participants. Through the interviews, the 6 themes of: Comprehension, Inadequate response definition, Reference Point, Relevance, Perspective Modifiers and Calibration Across Items emerged. The items of working above the shoulder (90%), compensating with the unaffected arm (88%) and lifting heavy objects (92%) were the most relevant to participants. Participants calibrated their scores on the items of sleeping and styling (19%) the most. Perspective modifiers of gender, influenced the calibrations of items of styling your hair (30%) and dressing or undressing (19%). Compensatory strategies of task-re allocation and using assistive devices/resources were frequently mentioned by participants. Overall, participants had minor comprehension issues, but found the 7- items of the Short-WORC to be relevant to QoL. Conclusions Therefore, the findings demonstrate that the Short-WORC is not cognitively complex, but varies with patient perspectives. Overall, the Short-WORC provides evidence of demonstrating strong content validity when used for rotator cuff disorder patients.

Objectives Multiple intra- and inter-individual variabilities sculpt the experience of pain. However, integration of sex and gender has been under-explored in explanatory models of pain. This study aimed to examine the role of sex and traditionally genderized interpersonal-expressive traits, and their interactions in explaining the variability of pain ratings. Methods Data from 113 participants following acute non-catastrophic musculoskeletal (MSK) injuries were included. Participants completed the Brief Pain Inventory (BPI) and the Gender, Pain and Expectations Scale (GPES). An independent T-test was used to compare differences in BPI subscales between the sexes. Pearson correlations explored the associations between BPI and GPES subscale scores for the overall sample and also for the sample when disaggregated by sex. Multiple linear regression was used to investigate the interaction of sex and gender traits in explaining the BPI scores. Results No differences were found between the sexes in mean BPI Severity and Interference. Across sexes, Relationship-oriented was positively associated with greater BPI Severity (r = 0.20) and Emotive was positively associated with BPI Interference (r = 0.24). In sex-disaggregated analyses, these associations were significant in females only. Goal-oriented was associated with neither BPI Severity nor Interference. In multivariate regression, only Emotive was a significant predictor of BPI Interference. Discussion The findings suggest that variances in pain-related interference are partially explained by scores on a scale measuring self-perceptions of Emotive qualities. Sex was not predictive of either pain outcome in both bivariate and multivariate analyses. Researchers and clinicians are encouraged to consider both sex- and gender-based variables when interpreting patient pain reports.

Objective: To assess the extent and trends in registration of Orthopaedic randomized clinical trials (RCTs) between 2015 and 2020. Design: Epidemiological study. Primary publications of RCTs published in top Orthopaedic journals (ISI Journal Citation Reports 2019 rankings) between 2015 and 2020 were included in this meta-epidemiological study with no restrictions on patient population, intervention/control groups or outcome type. Independent reviewers in pairs were involved in RCT selection and data extraction. The proportion of RCTs published that were registered (prospectively or retrospectively) or not registered were reported using counts and percentages stratified by years for each journal. Results: A total of 474 primary RCTs were considered eligible. We identified 157 out of 474 RCTs (33% of RCTs across journals) that were reported to have been registered prospectively.The proportion of prospective RCT registrations had increased by 40% (10%–50%) between 2015 and 2020. On the other hand, the proportion of RCTs with no registrations were reduced by 29% (50%–21%) between 2015 and 2020. Conclusion: Prospective RCT registration in the past 5 years in the field of orthopaedic has increased, but 2/3 of published RCTs still failed to report prospective registration.

Background: Several studies have assessed the impact of the COVID-19 pandemic on anxiety and depression, but have not focused on the role of sex and gender. This study compared changes in the levels of anxiety and depression (pre- and post-COVID) experienced by individuals of various sexes and genders. Methods: We used a cross-sectional online survey that assessed pre- and post-COVID symptoms of anxiety (Generalized Anxiety Disorder-2) and depression (Patient Health Questionnaire-9). General linear modeling (fixed model factorial analysis of variance) was used to evaluate changes in anxiety and depression between pre- and post-pandemic periods and explore differential effects of sex and gender on those changes. Results: Our study included 1847 participants from 43 countries and demonstrated a percentage increase of 57.1% and 74.2% in anxiety and depression, respectively. For the Generalized Anxiety Disorder-2 scale (maximum score 6), there was a mean increase in anxiety by sex for male, female, and other of 1.0, 1.2, and 1.4, respectively; and by gender for man, woman, and others of 0.9, 1.3, and 1.6, respectively. For the Patient Health Questionnaire-9 (maximum score 27), there was a mean increase in depressive symptoms by sex for male, female, and other of 3.6, 4.7, and 5.5 respectively; and by gender for man, woman, and others of 3.3, 4.8, and 6.5, respectively. Conclusion: During COVID-19, there was an increase in anxiety and depressive symptoms for all sexes and genders, with the greatest increases reported by those identifying as non-male and non-men.

Content validity is a fundamental requirement of outcome measures. After reviewing operational needs and existing definitions, content validity we as defined as: the extent to which a measure provides a comprehensive and true assessment of the key relevant elements of a specified construct or attribute across a defined range, clearly and equitably for a stated target audience and context. ICF linkage rules from 2002, 2005, and 2019 have provide increasingly clear processes for describing and evaluating content of outcome measures. ICF Core Sets provide international reference standards of the core constructs of importance for different health conditions. Both are important as reference standards during content validation. To summarize their use as reference standards, the following summary indicators were proposed: (1) Measure to ICF linkage, (2) Measure to (Brief or Comprehensive) Core Set Absolute Linkage, (3) Measure to (Brief or Comprehensive) Core Set Unique Linkage, (4) Core Set Representation, and (5) Core Set Unique Disability Representation. Methods to assess how respondents engage with content are needed to complement ICF-linking. Cognitive interviewing is an ideal method since it used to explore how respondents interpret and calibrate response to individual items on an outcome measure. We proposed a framework for classifying these responses: Clarity/Comprehension, Relevance, Inadequate response definition, Reference Point, Perspective modification, and Calibration Across Items. Our analysis of 24 manuscripts that used ICF linking for content validation since updated linking rules were published found that authors typically used linking to validate existing measures, involved multiple raters, used 2005 linking rules, summarized content at a concept level (e.g., impairment, activity, participation) and/or use core sets as a reference standard. Infrequently, ICF linking was used to create item pools/conceptual frameworks for new measures, applied the full scope of the 2019 linking rules, used summary indicators, or integrated ICF-linking with qualitative methods like cognitive interviews. We conclude that ICF linkage is a powerful tool for content validity during development or validation of PROM. Best practices include use of updated ICF linking rules, triangulation of ICF linking with participant assessments of clarity and relevance preferably obtained using cognitive interview methods, and application of defined summary indicators.

Abstract Background To evaluate the translations, cross-cultural adaptation procedures and measurement properties of the Western Ontario Rotator Cuff Index (WORC), when it is adapted for different cultures. Methods A systematic review was performed, considering different cultural adaptions of the WORC accessible through MEDLINE, CINAHL, EMBASE and/or Google Scholar. Included were prospective cohort studies that used an adapted version of the WORC to measure QoL in patients with rotator cuff disorders. All studies were evaluated according to the current guidelines for cross-cultural adaptations and measurement properties. Results The search retrieved 14 studies that met the inclusion criteria. According to the recommended guidelines for cross-cultural adaptations, 8 studies performed 100% of the steps, 2 studies performed 80% of the steps and 4 studies used previously translated measures. When evaluating the studies’ psychometric properties based on the quality criteria, none of the studies reported all recommended measurement properties. All of the studies reported the measurement property of reliability, but none of the studies reported agreement. Internal consistency was fully reported by 15% of studies. Construct validity was reported by 43% of studies. Only one study reported 100% of the cross-cultural adaption guidelines and 83% of the quality criteria. Conclusions Although the majority of studies demonstrated proper adaptation procedures, testing of the measurement properties were inadequate. It is recommended that the current adapted versions of the WORC undergo further testing before use in clinical practise, and researchers continue to adapt the WORC for different cultures as it proves to be an appropriate instrument for assessing rotator cuff pathology.

Abstract Background Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods. Results Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception. Conclusions These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity.

Abstract Background The anti–interleukin-6 receptor-alpha antibody tocilizumab was approved for intravenous (IV) injection in the treatment of patients with systemic juvenile idiopathic arthritis (sJIA) aged 2 to 17 years based on results of a randomized controlled phase 3 trial. Tocilizumab treatment in systemic juvenile idiopathic arthritis (sJIA) patients younger than 2 was investigated in this open-label phase 1 trial and compared with data from the previous trial in patients aged 2 to 17 years. Methods Patients younger than 2 received open-label tocilizumab 12 mg/kg IV every 2 weeks (Q2W) during a 12-week main evaluation period and an optional extension period. The primary end point was comparability of pharmacokinetics during the main evaluation period to that of the previous trial (in patients aged 2–17 years), and the secondary end point was safety; pharmacodynamics and efficacy end points were exploratory. Descriptive comparisons for pharmacokinetics, pharmacodynamics, safety, and efficacy were made with sJIA patients aged 2 to 17 years weighing

Abstract Background The development and spread of artemisinin-resistant Plasmodium falciparum malaria in Greater Mekong Subregion has created impetus for continuing global monitoring of efficacy of artemisinin-based combination therapies (ACTs). This post analyses is aimed to evaluate changes in early treatment response markers 10 years after the adoption of ACTs as first-line treatments of uncomplicated falciparum malaria in Nigeria. Methods At 14 sentinel sites in six geographical areas of Nigeria, we evaluated treatment responses in 1341 children under 5 years and in additional 360 children under 16 years with uncomplicated malaria enrolled in randomized trials of artemether-lumefantrine versus artesunate-amodiaquine at 5-year interval in 2009–2010 and 2014–2015 and at 2-year interval in 2009–2010 and 2012–2015, respectively after deployment in 2005. Results Asexual parasite positivity 1 day after treatment initiation (APPD1) rose from 54 to 62% and 2 days after treatment initiation from 5 to 26% in 2009–2010 to 2014–2015 (P = 0.002 and P 75 000 μl− 1, haematocrit > 27% 1 day post-treatment initiation, treatment with artemether-lumefantrine and enrolment in 2014–2015 independently predicted APPD1. In parallel, Kaplan-Meier estimated risk of recurrent infections by day 28 rose from 8 to 14% (P = 0.005) and from 9 to 15% (P = 0.02) with artemether-lumefantrine and artesunate-amodiaquine, respectively. Mean asexual parasitaemia half-life increased significantly from 1.1 h to 1.3 h within 2 years (P

Abstract Background To determine the known-group validity, a type of construct validity, and the test-retest reliability of a newly developed tool, the Personalized Exercise Questionnaire (PEQ), that assesses the barriers, facilitators, and preferences to exercise in individuals with low bone mass and osteoporosis. Methods A comparative design was used to assess known-group validity and a test-retest design to examine the reproducibility. Ninety-five participants with low bone mass and osteoporosis were recruited from an outpatient clinic in Hamilton, Ontario. The questionnaire was administered to 95 participants at baseline and a subset of 42 participants completed the survey again one week later. The known-group validity of the PEQ was determined using four hypotheses that compared two known groups based on employment level, age, socioeconomic status, and physical activity level. The reproducibility of individual responses was analyzed using the Kappa Coefficient (κ). Results There was known-group validity for three of the four hypotheses. Test-retest reliability scores ranged from no agreement to almost perfect agreement; seven items had almost perfect agreement (κ: 0.81–1.00), 12 substantial agreement (κ: 0.68–0.74), six moderate agreement (κ: 0.56–0.60), two fair agreement (κ: 0.36–0.40), one slight agreement (κ = 0.23) and one no agreement (κ = − 0.03). Conclusion Preliminary support for the usefulness of the PEQ is indicated since the majority of the items had at least substantial agreement and known-group validity was moderately supported for some items. Trial registration This study was retrospectively registered with ClinicalTrials.gov, NCT03125590, on April 24, 2017.

Purpose: Older patients (aged older than 65 years) appear to tolerate a great degree of anatomic deformity after DRFs; however, the threshold beyond which the deformity becomes unacceptable is unknown. The purposes of this study were to identify the acceptable threshold for radiographic parameters after DRFs in patients aged over 65 years according to a patient-rated pain and disability outcome measure and to determine whether baseline activity levels influenced these parameters. Methods: A cohort of 190 older adults (aged 65 years and older) with DRF were selected from an existing prospectively collected database. The influence of specific radiographic parameters (ulnar variance, radial inclination [RI], and volar-dorsal tilt) and baseline activity levels on 1-year Patient-Rated Wrist Evaluation (PRWE) scores was investigated. The odds ratio (OR) of a poor outcome according to a 1-year PRWE (cutoff score of ≥25) at various alignment thresholds was calculated with 95% confidence intervals (CIs). Activity level (underactive vs active) was determined using the Rapid Assessment of Physical Activity survey. Results: Radiographic parameters for the cohort varied widely (mean ulnar variance, 1.9 ± 0.9 mm, range –2.4 to 8.0 mm; mean RI, 18.7°± 5.9°, range, 0.1° to 38°; and mean dorsal tilt, 4.5° ±11.9°, range –24.0° to 33.6°). Most of the cohort (n = 158, 83%) had a good outcome (mean PRWE, 14.4 ± 19.5). The OR of a poor outcome was significant for RI less than 20° (OR = 3.6; 95% CI 1.5–8.7) and dorsal tilt greater than 15° (OR = 5.3; 95% CI, 1.0–27.8). Malalignment on radiographs and a poor outcome according to PRWE were not significantly different in the underactive versus active subpopulations. Conclusions: This study provides alignment cutoffs that best discriminate adverse pain and disability patient outcomes after DRF in a cohort aged more than 65 years. This information can be used to counsel older patients about their increased likelihood of a poor outcome with RI less than 20˚ or a dorsal tilt greater than 15°. Further research is required to examine outcomes after applying these thresholds in a prospective manner to management decision algorithms for DRF in patients aged over 65 years. Type of study/level of evidence: Prognostic II. Key words: distal radius fracture, elderly, outcome

On-farm welfare assessment tends to focus on minimising negative welfare, but providing positive welfare is important in order to give animals a good life. This study developed a positive welfare framework for dairy cows based on the existing scientific literature which has focused on developing positive welfare indicators, and trialled a participatory approach with farmers; refining the framework based on their recommendations, followed by a vet pilot phase on farm. The results revealed that farmers and scientists agree on what constitutes “a good life” for dairy cattle. Farmers value positive welfare because they value their cows’ quality of life, and want to be proud of their work, improve their own wellbeing as well as receive business benefits. For each good life resource, the proportion of farmers going above and beyond legislation ranged from 27 to 84%. Furthermore, barriers to achieving positive welfare opportunities, including monetary and time costs, were not apparently insurmountable if implementation costs were remunerated (by the government). However, the intrinsic value in providing such opportunities also incentivises farmers. Overall, most farmers appeared to support positive welfare assessment, with the largest proportion (50%) supporting its use within existing farm assurance schemes, or to justify national and global marketing claims. Collaborating with farmers to co-create policy is crucial to showcase and quantify the UK’s high welfare standards, and to maximise engagement, relevance and uptake of animal welfare policy, to ensure continuous improvement and leadership in the quality of lives for farm animals.

Purpose: Lymphedema is a common debilitating late effect among patients post-head and neck cancer (HNC) treatment. Head and neck lymphedema was associated with symptom burden, functional impairment, and decreased quality of life. The objective of this study was to determine the feasibility and potential efficacy of the use of photobiomodulation (PBM) therapy for head and neck lymphedema, symptom burden, and neck range of motion among HNC survivors. Methods: This was a single-arm, pre- and post-design clinical trial. Eligible patients included those with lymphedema after completion of complete decongestive therapy (CDT) and 3 to 18 months after completion of cancer therapy. The intervention included PBM therapy 2 times a week for 6 weeks for a total of 12 treatments. Lymphedema, symptom burden, and neck range of motion were measured at baseline, end-of-intervention, and 4-week post-intervention. Results: Of the 12 patients enrolled in the study, 91.7% (n = 11) completed the study intervention and assessment visits, and no adverse events were reported. When comparing the baseline to 4-week post-intervention, we found statistically significant improvements in the severity of external lymphedema, symptom burden, and neck range of motion (all P

This study investigated the influence of maternal level of education and socioeconomic status on maternal knowledge of nutrition, physical activity, and children’s body weight of Nigerian school pupils. A total of four hundred and twelve (412) primary school pupils participated in this study. A structured questionnaire was used to assess the maternal level of education, material’s knowledge of nutrition, and physical activities. Body height and body weight were measured with a wall-mounted stadiometer in meters and a bathroom weighing scale in kg, respectively. The children’s body weight was determined using the formula weight (kg)/height (m2). The children were then categorized into different classes of body mass index based on the recommendation of Centers for Diseases Control and Prevention (2015), which is age and sex-specific for children and teens from two years old through 20 years. The differences in maternal educational qualification and children’s bodyweights were analyzed using the independent sample t-test. However, the influence of maternal SES on maternal knowledge of nutrition, physical activities, and children’s body weights were analyzed using ANOVA. Statistical significance was accepted for a p-value of

Despite significant progress in the treatment of patients with diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), the prognosis of patients with relapsed disease remains poor due to the emergence of drug resistance and subsequent disease progression. Identification of novel targets and therapeutic strategies for these diseases represents an urgent need. Here, we report that both MCL and DLBCL are exquisitely sensitive to transcription-targeting drugs, in particular THZ531, a covalent inhibitor of cyclin-dependent kinase 12 (CDK12). By implementing pharmacogenomics and a cell-based drug screen, we found that THZ531 leads to inhibition of oncogenic transcriptional programs, especially the DNA damage response pathway, MYC target genes and the mTOR-4EBP1-MCL-1 axis, contributing to dramatic lymphoma suppression in vitro. We also identified de novo and established acquired THZ531-resistant lymphoma cells conferred by over-activation of the MEK-ERK and PI3K-AKT-mTOR pathways and upregulation of multidrug resistance-1 (MDR1) protein. Of note, EZH2 inhibitors reversed resistance to THZ531 by competitive inhibition of MDR1 and, in combination with THZ531, synergistically inhibited MCL and DLBCL growth in vitro. Our study indicates that CDK12 inhibitors, alone or together with EZH2 inhibitors, offer promise as novel effective approaches for difficult-to-treat DLBCL and MCL.

Objectives: The objectives of this study were to identify contextual factors as barriers or facilitators of osteoarthritis management in urban- and rural-dwelling seniors by applying the World Health Organization’s International Classification of Functioning, Disability and Health (ICF). Design: Secondary analysis was performed on interview transcripts from urban- (n ​= ​11) and rural-dwelling (n ​= ​9) seniors living with osteoarthritis in Canada. Meaningful concepts were linked to ICF codes (Environmental Factors) according to established linking rules. Unclassified content (including Personal Factors) was subjected to qualitative content analysis. Results: A total of 481 and 410 meaningful concepts were identified in interview transcripts from urban and rural groups, respectively. For Environmental Factors, the majority of meaningful concepts linked to “Environmental Factors”, then “Activities and Participation”, and then “Body Functions” in the ICF. The most frequently linked codes were “e355 Health professionals”, “e5801 Health systems”, “e5800 Health services”, and “e398 Support and relationships, other specified”. The most salient barrier and facilitator to osteoarthritis management reflected in our results were “e5801 Health systems” and “e398 Support and relationships, other specified”, respectively, for both urban and rural groups. For Personal Factors, qualitative content analysis of unclassified content revealed 3 key themes including (1) Coping Strategies; (2) Age of Osteoarthritis Diagnosis; and (3) Individual Circumstances. Conclusion: Beyond physical limitations, community-dwelling seniors with osteoarthritis encounter a wide range of biopsychosocial factors that can impact disease management. Applying the ICF, we identify “Environmental Factors” as a significant contextual factor impacting osteoarthritis management in both urban and rural communities.

Background: Immunisation documentation in India has historically been fragmented over a number of systems. To reduce errors and wasted vaccinations for one of the largest and most complex public vaccination systems, data storage has migrated to electronic application-based data records. However, the system remains fragmented. There has been much interest in the global health sector about the use of blockchain technology to build secure, immutable databases for complex data in fragmented environments. As part of the Indian government's innovation initiatives, our project aims to describe a blockchain immunisation system to store immunisation data, pilot its use in India, and assess strengths, limitations, and feasibility of blockchain immunisation. Methods: A connector database—Anveshan—was developed for the state of Gujarat, India, to: (1) remove data fragmentation; (2) enable aggregate analysis to allow tracking of dynamic data; (3) track data changes; and (4) enable fault tolerance so data can be accurately preserved for long periods of time. Although live piloting was not possible because of the COVID-19 pandemic, a simulated pilot was done. A report including lessons learned, benefits and challenges of blockchain application to immunisation documentation, and recommendations for future usage was delivered. Findings: Results from the simulation showed that the Anveshan database was able to decrease data fragmentation by querying across both supply and delivery databases. Aggregate analysis capability was increased through development of a dashboard user interface that allowed policymakers and immunisation programme staff to receive real-time query feedback. Data changes could be tracked and private data encrypted by incorporating disincentives for inappropriate data modification. Blockchain technology properties increased fault tolerance, which make data less corruptible. Although blockchain technology offers benefits for data storage, it does not facilitate improvements in data collection and quality, which remain a significant challenge in India. Multiple health-care stakeholders would need to work together and have access to live data to ensure nationwide scalability. Interpretation: Our findings show the challenges and benefits of a private blockchain system and identify areas requiring continued improvement for immunisation documentation in India. One important consideration in infrastructure design on a nationwide scale is the design of the blockchain system itself. This study is an important first step to show that evidence-based design innovation using blockchain can help countries such as India to address complex public health-care delivery conundrums. Funding: India Grand Challenges grant (Bill & Melinda Gates Foundation and BIRAC, Government of India).

Prostate cancer is one of the most common malignant tumors in men. Initially, it is androgen-dependent, but it eventually develops into castration-resistant prostate cancer (CRPC), which is incurable with current androgen receptor signaling target therapy and chemotherapy. Immunotherapy, specifically with immune checkpoint inhibitors, has brought hope for the treatment of this type of prostate cancer. Approaches such as vaccines, adoptive chimeric antigen receptor-T (CAR-T) cells, and immune checkpoint inhibitors have been employed to activate innate and adaptive immune responses to treat prostate cancer, but with limited success. Only Sipuleucel-T and the immune checkpoint inhibitor pembrolizumab are approved by the US FDA for the treatment of limited prostate cancer patients. Prostate cancer has a complex tumor microenvironment (TME) in which various immunosuppressive molecules and mechanisms coexist and interact. Additionally, prostate cancer is considered a “cold” tumor with low levels of tumor mutational burden, low amounts of antigen-presenting and cytotoxic T-cell activation, and high levels of immunosuppressive molecules including cytokines/chemokines. Thus, understanding the mechanisms of immunosuppressive signaling activation and immune evasion will help develop more effective treatments for prostate cancer. The purpose of this review is to summarize emerging advances in prostate cancer immunotherapy, with a particular focus on the molecular mechanisms that lead to immune evasion in prostate cancer. At the same time, we also highlight some potential therapeutic targets to provide a theoretical basis for the treatment of prostate cancer.

BackgroundThe Objective Structured Clinical Examination (OSCE) is a commonly used tool internationally to assess clinical competency. Physical therapy (PT) licensure processes vary internationally. The OSCE is the tool used in Canada to assess clinical competency for PT graduates seeking licensure. Previous studies that examined the measurement properties of OSCEs present contradictory results.ObjectivesThe first objective was to investigate the reliability and validity of OSCEs when administered to PTs during their education or as part of a licensure process. The second objective was to conduct a structured review to report PT educational and licensing components and policies in 17 countries with well-developed PT regulation systems.MethodsAn electronic search was performed in four databases from inception to 31st March 2021 to identify relevant articles. Two reviewers performed the critical appraisal of the included studies using a validated quality assessment tool. We deployed a random effects meta-analysis on reliability and validity estimates of OSCEs and examined sources of heterogeneity with univariate meta-regressions. We searched websites of professional regulatory bodies and associations for data on educational and licencing components and policies. Educational and licensing components across countries were synthesized descriptively.ResultsA pooled estimate of Cronbach's alpha of 0.55, (95% CI: 0.41, 0.67) was determined for OSCEs. The pooled estimate of Intraclass Correlation Coefficient (ICC) between assessors was 0.77 (95% CI: 0.70, 0.83). The pooled estimate of Pearson Correlation between multiple OSCE stations' scores was 0.27 (95% CI: 0.15, 0.39); and between each station score and the total score was 0.71 (95% CI: 0.61, 0.79). The pooled estimates for kappa Coefficients were 0.75 (95% CI: 0.58, 0.86) and 0.84, (95% CI: 0.72, 0.91) for intra-rater and inter-rater reliability of the standardised patient respectively. From the 17 included countries, Canada (excluding Quebec) was the only country that required both a clinical and written competency exam following graduation from an accredited PT program. Two countries (USA, UAE) required a written competency exam. The remaining 14 countries did not require an additional competency examination after completion of degree requirements from an accredited program.ConclusionsWe found weak evidence that OSCE examinations items are internally consistent when used to assess PTs. Canada (excluding Quebec) is the only country out of 17 implementing a national clinical competency examination for their PT graduates to achieve licensure after completing professional degree requirements.

Objectives: To determine the factor structure and test the clinometric properties of wrist and hand version of the Patient-Rated Wrist Evaluation. Design: Cross-sectional study using Rasch analysis and factor analysis. Confirmatory factor analysis was conducted to assess the factor structure. Higher-order factor analysis was used to explore the hierarchical structure of the items. The Rasch model was used to assess the overall fit, reliability, validity, and construct unidimensionality. Rasch analysis and factor analysis were conducted using RUMM2030 and LISREL software, respectively. Setting: Outpatient hand rehabilitation clinic. Participants: A convenience sample of patients (N=206) with various hand injuries who completed the Persian version of the Patient-Rated Wrist and Hand Evaluation (PRWHE-P) at 2 months postinjury. The study included 66 men and 139 women, with a mean age of 40 years. Intervention: Not applicable. Main Outcome Measures: The PRWHE-P was used as a patient-reported measure of pain and disability in wrist and hand conditions. Results: Factor analysis confirmed 3-factor models of the PRWHE-P. Items fit well to the Rasch model in 3 subscales. The PRWHE-P had a good item reliability (0.82) and good internal consistency (0.8). No differential item functioning was detected for age, sex, dominant hand, or injured hand. Conclusions: The results of this study indicated that the PRWHE-P with 3 sub scales is a reliable and valid measurement tool and could be used in patients with different wrist and hand disabilities.

Objective: To investigate the efficacy of fall hazards identification programs when compared to no intervention or other fall prevention programs on number of falls, falls incidence, and identifying fall hazards in community-dwelling adults. Data Sources: CINAHL, PubMed, EMBASE, Scopus, and PsychINFO were used to identify articles. Study Selection: Studies were selected to compare fall hazards identification programs to a control group. Studies were eligible if they were randomized controlled trials and enrolled adults older than 50 years with the incidence rate of falls as an outcome. Data Extraction: Study or authors, year, sample characteristics, intervention or comparison groups, number of falls, and number of hazards identified in the intervention and control groups, and follow-up were extracted. The risk of bias assessment was performed using the Cochrane Risk of Bias tool. Quality was evaluated with Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach per outcome. Data Synthesis: A total of 8 studies (N=8) and 5177 participants were included. There was a high risk of bias across the studies mostly due to improper blinding of personnel of the outcome assessor. Pooled estimate effects from 5 studies assessing the incidence rate of falls from 3019 individuals indicated no difference between fall hazards identification programs and control (incidence rate ratio=0.98; 95% confidence interval, 0.87-1.10). Conclusions: The current study suggests that there may be a benefit for fall hazards programs in reducing incident falls. However, because of a moderate GRADE rating, more large-scale studies with a higher number of falls events and more consistent control groups are required to determine the true effect.

Social inequity can have broad health impacts. The purpose of this study was to examine the effects of low income and nonadherence to health supervision visits on emergency room (ER) utilization in Eastern Brooklyn, New York. This study surveyed parents/guardians of children who received routine medical care at Brookdale ambulatory clinics from June 2017 to February 2018. Participants were asked to fill out a questionnaire on social demographics, food insecurity, and relocation. Electronic medical records (EMRs) were reviewed to retrieve numbers of missing health supervision and ER visit in past 12 months. Comorbidity was identified through EMR by International Classification of Diseases. Logistic regression analyses were used to examine the effects of nonadherence to health supervision visits on ER utilization when controlling for demographics, food insecurity, recent moving, and comorbidity. Among 268 participants, 56.0% reported their household income was less than $20,000 annually, 39.6% missed at least 1 health supervision visit, and 31.7% had at least 1 ER visit within the past 12 months. Younger age (adjusted odds ratio [aOR] = 0.92, 95% confidence interval [CI] = 0.86-0.97, P < .01), household income less than $20,000 (aOR = 1.86, 95% CI = 1.02-3.39), preexisting comorbidity (aOR = 2.36, 95% CI = 1.26-4.42), and nonadherence to health supervision visits (aOR = 5.83, 95% CI = 3.21-10.56) were associated with increased ER utilization. Nonadherence to health supervision visits is an independent risk factor and potentially modifiable. Evaluation and remediation should be pursued as a means of improving health outcomes of children in vulnerable circumstances.

Abstract Background Patient-reported outcome measures developed using Classical Test Theory are commonly comprised of ordinal level items on a Likert response scale are problematic as they do not permit the results to be compared between patients. Rasch analysis provides a solution to overcome this by evaluating the measurement characteristics of the rating scales using probability estimates. This is typically achieved using commercial software dedicated to Rasch analysis however, it is possible to conduct this analysis using non-specific open source software such a R. Methods Rasch analysis was conducted using the most commonly used commercial software package, RUMM 2030, and R, using four open-source packages, with a common data set (6-month post-injury PRWE Questionnaire responses) to evaluate the statistical results for consistency. The analysis plan followed recommendations used in a similar study supported by the software package’s instructions in order to obtain category thresholds, item and person fit statistics, measures of reliability and evaluate the data for construct validity, differential item functioning, local dependency and unidimensionality of the items. Results There was substantial agreement between RUMM2030 and R with regards for most of the results, however there are some small discrepancies between the output of the two programs. Conclusions While the differences in output between RUMM2030 and R can easily be explained by comparing the underlying statistical approaches taken by each program, there is disagreement on critical statistical decisions made by each program. This disagreement however should not be an issue as Rasch analysis requires users to apply their own subjective analysis. While researchers might expect that Rasch performed on a large sample would be a stable, two authors who complete Rasch analysis of the PRWE found somewhat dissimilar findings. So, while some variations in results may be due to samples, this paper adds that some variation in findings may be software dependent.

When people discuss "Market Rabbits," they often think only of using rabbits for their meat. However, in this Florida 4-H project, youth have the opportunity to study not only meat rabbit production, but also the textile rabbit markets and pet or show stock production for their market project. In the 4-H Market Rabbit project (visit http://florida4h.org for more information about this online project), youth learn the skills necessary for choosing and maintaining healthy rabbit stock, proper handling of rabbits, rabbit health, and general care in addition to producing rabbits for a profit. This document, the Market Rabbit Record Book (4H RAR 13), familiarizes youth with the importance of record keeping as an integral part of project management. Records help youth keep track of vital information that can later help them make the best decisions regarding their animals. By tracking inventory, financial records associated with their project, rabbit health and growth details, industry-specific information such as wool/meat/kit yield, as well as pedigree/breeding and identification methods and dates, youth will be well prepared to relate their experiences in a written narrative as part of their project completion activities. Original publication date September 2010.

Pet rabbits are chosen primarily for their temperment, more so than for their looks. They are generally calm animals that can be easily handled and cared for. In the 4-H Pet Rabbit project (visit http://florida4h.org for more information about this online project), youth learn the skills necessary for choosing a healthy rabbit, proper handling of a rabbit, rabbit health, and general care. This document, the Pet Rabbit Record Book (4H RAR 11), familiarizes youth with the importance of record keeping as an integral part of project management. By tracking inventory, financial records associated with their project, rabbit health and grooming details, and related information, youth will be well prepared to relate their experiences in a written narrative as part of their project completion activities. Original publication date September 2010.

We conducted an intercontinental biogeographic survey to analyze the effects of an invasive plant species in its native and invaded ranges. Our study system included tidal wetlands colonized by Iris pseudacorus L. (yellow flag iris, Iridaceae) along salinity gradients in two estuaries in its native European (Guadalquivir Estuary) and invaded North American (San Francisco Bay-Delta Estuary) ranges. We hypothesized I. pseudacorus would impart more negative community-level impacts on plant species diversity in the invaded range compared to the native range. Our results show that the colonization of Iris pseudacorus has very different effects on the diversity of tidal plant communities in its native and invaded ranges. In the native range, I. pseudacorus promoted plant diversity by increasing evenness and species richness. On the contrary, I. pseudacorus greatly reduced plant diversity in the invaded range, being this reduction higher in those communities with higher species richness and diversity levels. In view of these results, urgent management practices are needed to control and eradicate I. pseudacorus from the inland Sacramento-San Joaquin Delta Estuary since this invasive macrophyte is reducing plant diversity at local and landscape scales.

Abstract Background In acute falciparum malaria, asexual parasite reduction ratio two days post-treatment initiation (PRRD2) ≥ 10 000 per cycle has been used as a measure of the rapid clearance of parasitaemia and efficacy of artemisinin derivatives. However, there is little evaluation of alternative measures; for example, parasite reduction ratio one day after treatment initiation (PRRD1) and its relationship with parasite clearance time (PCT) or PRRD2. This study evaluated the use of PRRD1 as a measure of responsiveness to antimalarial drugs. Methods In acutely malarious children treated with artesunate-amodiaquine (AA), artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DHP), the relationships between PRRD1 or PRRD2 and PCT, and between PRRD1 and PRRD2 were evaluated using linear regression. Agreement between estimates of PCT using PRRD1 and PRRD2 linear regression equations was evaluated using the Bland-Altman analysis. Predictors of PRRD1 > 5000 per half cycle and PRRD2 ≥ 10 000 per cycle were evaluated using stepwise multiple logistic regression models. Using the linear regression equation of the relationship between PRRD1 and PCT previously generated in half of the DHP-treated children during the early study phase, PCT estimates were compared in a prospective blinded manner with PCTs determined by microscopy during the later study phase in the remaining half. Results In 919 malarious children, PRRD1 was significantly higher in DHP- and AA-treated compared with AL-treated children (P 15 months, parasitaemia > 10 000/μl and DHP treatment independently predicted PRRD1 > 5000 per half cycle, while age > 30 months, haematocrit ≥31%, body temperature > 37.4 °C, parasitaemia > 100 000/μl, PRRD1 value > 1000 and no gametocytaemia independently predicted PRRD2 ≥ 10 000 per cycle. Using the linear regression equation generated during the early phase in 166 DHP-treated children, PCT estimates and PCTs determined by microscopy in the 155 children in the later phase were similar in the same patients. Conclusions PRRD1 and estimates of PCT using PRRD1 linear regression equation of PRRD1 and PCT can be used in therapeutic efficacy studies. Trial registration Pan African Clinical Trial Registration PACTR201709002064150, 1 March 2017, http://www.pactr.org

The AR-V7 isoform is associated with anti-androgen drug resistance in prostate cancer. Here, the authors show that AR-V7 protein stability is regulated by HSP70/STUB1 complex-mediated proteostasis which confers drug resistance in late stage prostate cancer. Inhibition of HSP70 re-sensitizes resistant cells to enzalutamide therapy.

Abstract Background Outcome after nerve repair of the hand needs standardized psychometrically robust measures. We aimed to systematically review the psychometric properties of available functional, motor, and sensory assessment instruments after nerve repair. Methods This systematic review of health measurement instruments searched databases from 1966 to 2017. Pairs of raters conducted data extraction and quality assessment using a structured tool for clinical measurement studies. Kappa correlation was used to define the agreement prior to consensus for individual items, and intraclass correlation coefficient (ICC) was used to assess reliability between raters. A narrative synthesis described quality and content of the evidence. Results Sixteen studies were included for final critical appraisal scores. Kappa ranged from 0.31 to 0.82 and ICC was 0.81. Motor domain had manual muscle testing with Kappa from 0.72 to 0.93 and a dynamometer ICC reliability between 0.92 and 0.98. Sensory domain had touch threshold Semmes-Weinstein monofilaments (SWM) as the most responsive measure while two-point discrimination (2PD) was the least responsive (effect size 1.2 and 0.1). A stereognosis test, Shape and Texture Identification (STI), had Kappa test-retest reliability of 0.79 and inter-rater reliability of 0.61, with excellent sensibility and specificity. Manual tactile test had moderate to mild correlation with 2PD and SWM. Function domain presented Rosén-Lundborg score with Spearman correlations of 0.83 for total score. Patient-reported outcomes measurements had ICC of 0.85 and internal consistency from 0.88 to 0.96 with Patient-Rated Wrist and Hand Evaluation with higher score for reliability and Spearman correlation between 0.38 and 0.89 for validity. Conclusions Few studies included nerve repair in their sample for the psychometric analysis of outcome measures, so moderate evidence could be confirmed. Manual muscle test and Rotterdam Intrinsic Hand Myometer dynamometer had excellent reliability but insufficient data on validity or responsiveness. Touch threshold testing was more responsive than 2PD test. The locognosia test and STI had limited but positive supporting data related to validity. Rosén-Lundborg score had emerging evidence of reliability and validity as a comprehensive outcome following nerve repair. Few questionnaires were considered reliable and valid to assess cold intolerance. There is no patient-reported outcome measurement following nerve repair that provides comprehensive assessment of symptoms and function by patient perspective.

Summary: We studied 137 primary testicular germ cell tumors (TGCTs) using high-dimensional assays of genomic, epigenomic, transcriptomic, and proteomic features. These tumors exhibited high aneuploidy and a paucity of somatic mutations. Somatic mutation of only three genes achieved significance—KIT, KRAS, and NRAS—exclusively in samples with seminoma components. Integrated analyses identified distinct molecular patterns that characterized the major recognized histologic subtypes of TGCT: seminoma, embryonal carcinoma, yolk sac tumor, and teratoma. Striking differences in global DNA methylation and microRNA expression between histology subtypes highlight a likely role of epigenomic processes in determining histologic fates in TGCTs. We also identified a subset of pure seminomas defined by KIT mutations, increased immune infiltration, globally demethylated DNA, and decreased KRAS copy number. We report potential biomarkers for risk stratification, such as miRNA specifically expressed in teratoma, and others with molecular diagnostic potential, such as CpH (CpA/CpC/CpT) methylation identifying embryonal carcinomas. : Shen et al. identify molecular characteristics that classify testicular germ cell tumor types, including a separate subset of seminomas defined by KIT mutations. This provides a set of candidate biomarkers for risk stratification and potential therapeutic targeting. Keywords: The Cancer Genome Atlas, testicular germ cell tumors, seminoma, nonseminoma, DNA methylation, exome sequencing, KIT, copy number, miR-375

Background: To explore the differences in young adult male and female attitudes towards and motivations for suicide, beliefs about help-seeking behavior, and attitudes towards helping others to prevent suicide. Methods: In-depth interviews and focus groups with adolescent and young adult males and females (n = 50, ages 14–24) were conducted before and after a community-based play on suicide prevention. Two focus groups and 30 individual interviews (n = 50, 22 males, 28 females) were conducted before the intervention at one location, and 12 in-depth interviews (4 males, 8 females) were conducted with some of the same individuals after the play. The transcripts were coded by two independent coders for gender differences. Emergent categories were analyzed to identify differences in responses to issues surrounding suicide and depression. Results: Three key gender differences were found in communication styles around emotional vulnerabilities: (1) Females were more likely to talk about the importance of reaching out to others and giving counsel, while males were more likely to expect others in need to seek them out for help. (2) Females talked about psychological distress as something “everyone” experiences, while males tended to see their suffering as an individual phenomenon. (3) Females tended to advocate disclosure while males talked about the pressure not to talk about personal problems. Conclusions: Young males and females may need different coping strategies, and interventions, therefore, must be tailored to address the needs of each gender separately. Campaigns and programs specifically for men should address the barriers that men face with disclosure and help-seeking, and strategies should be sensitive to the expectations of heteronormative masculinity.

Treatment-induced neuroendocrine prostate cancer (t-NEPC) often arises from adenocarcinoma via lineage plasticity in response to androgen receptor signaling inhibitors, such as enzalutamide. However, the specific regulators and targets involved in the transition to NEPC are not well understood. Plexin D1 (PLXND1) is a cellular receptor of the semaphorin (SEMA) family that plays important roles in modulating the cytoskeleton and cell adhesion. Here, we found that PLXND1 was highly expressed and positively correlated with neuroendocrine markers in patients with NEPC. High PLXND1 expression was associated with poorer prognosis in prostate cancer patients. Additionally, PLXND1 was upregulated and negatively regulated by androgen receptor signaling in enzalutamide-resistant cells. Knockdown or knockout of PLXND1 inhibited neural lineage pathways, thereby suppressing NEPC cell proliferation, patient derived xenograft (PDX) tumor organoid viability, and xenograft tumor growth. Mechanistically, the heat shock protein 70 (HSP70) regulated PLXND1 protein stability through degradation, and inhibition of HSP70 decreased PLXND1 expression and NEPC organoid growth. In summary, our findings indicate that PLXND1 could serve as a promising therapeutic target and molecular marker for NEPC.

Abstract Background Technological development and improvements in Wearable Physiological Monitoring devices, have facilitated the wireless and continuous field-based monitoring/capturing of physiologic measures in healthy, clinical or athletic populations. These devices have many applications for prevention and rehabilitation of musculoskeletal disorders, assuming reliable and valid data is collected. The purpose of this study was to appraise the quality and synthesize findings from published studies on psychometric properties of heart rate measurements taken with the Zephyr Bioharness device. Methods We searched the Embase, Medline, PsycInfo, PuMed and Google Scholar databases to identify articles. Articles were appraised for quality using a structured clinical measurement specific appraisal tool. Two raters evaluated the quality and conducted data extraction. We extracted data on the reliability (intra-class correlation coefficients and standard error of measurement) and validity measures (Pearson/Spearman’s correlation coefficients) along with mean differences. Agreement parameters were summarised by the average biases and 95% limits of agreement. Results A total of ten studies were included: quality ratings ranged from 54 to 92%. The intra-class correlation coefficients reported ranged from 0.85–0.98. The construct validity coefficients compared against gold standard calibrations or other commercially used devices, ranged from 0.74–0.99 and 0.67–0.98 respectively. Zephyr Bioharness agreement error ranged from − 4.81 (under-estimation) to 3.00 (over-estimation) beats per minute, with varying 95% limits of agreement, when compared with gold standard measures. Conclusion Good to excellent quality evidence from ten studies suggested that the Zephyr Bioharness device can provide reliable and valid measurements of heart rate across multiple contexts, and that it displayed good agreements vs. gold standard comparators – supporting criterion validity.

Abstract Background The Patient-Rated Wrist Evaluation (PRWE) was developed as a wrist joint specific measure of pain and disability and evidence of sound validity has been accumulated through classical psychometric methods. Rasch analysis (RA) has been endorsed as a newer method for analyzing the clinical measurement properties of self-report outcome measures. The purpose of this study was to evaluate the PRWE using Rasch modeling. Methods We employed the Rasch model to assess overall fit, response scaling, individual item fit, differential item functioning (DIF), local dependency, unidimensionality and person separation index (PSI). A convenience sample of 382 patients with distal radius fracture was recruited from the hand and upper limb clinic at large academic healthcare organization, London, Ontario, Canada, 6-month post-injury scores of the PRWE was used. RA was conducted on the 3 subscales (pain, specific activities, and usual activities) of the PRWE separately. Results The pain subscale adequately fit the Rasch model when item 4 “Pain - When it is at its worst” was deleted to eliminate non-uniform DIF by age group, and item 5 “How often do you have pain” was rescored by collapsing into 8 intervals to eliminate disordered thresholds. Uniform DIF for “Use my affected hand to push up from the chair” (by work status) and “Use bathroom tissue with my affected hand” (by injured hand) was addressed by splitting the items for analysis. After background rescoring of 2 items in pain subscale, 2 items in specific activities and 3 items in usual activities, all three subscales of the PRWE were well targeted and had high reliability (PSI = 0.86). These changes provided a unidimensional, interval-level scaled measure. Conclusion Like a previous analysis of the Patient-Rated Wrist and Hand Evaluation, this study found the PRWE could be fit to the Rasch model with rescoring of multiple items. However, the modifications required to achieve fit were not the same across studies, our fit statistics also suggested one of the pain items should be deleted. This study adds to the pool of evidence supporting the PRWE, but cannot confidently provide a Rasch-based scoring algorithm.

Abstract Background Despite the widely known benefits of exercise and physical activity, adherence rates to these activities are poor. Understanding exercise facilitators, barriers, and preferences may provide an opportunity to personalize exercise prescription and improve adherence. The purpose of this study was to develop the Personalized Exercise Questionnaire (PEQ) to identify these facilitators, barriers, and preferences to exercise in people with osteoporosis. Methods This study comprises two phases, instrument design and judgmental evidence. A panel of 42 experts was used to validate the instrument through quantitative (content validity) and qualitative (cognitive interviewing) methods. Content Validity Index (CVI) is the most commonly used method to calculate content validity quantitatively. There are two kinds of CVI: Item-CVI (I-CVI) and Scale-level CVI (S-CVI). Results Preliminary versions of this tool showed high content validity of individual items (I-CVI range: 0.50 to 1.00) and moderate to high overall content validity of the PEQ (S-CVI/UA = 0.63; S-CVI/Ave = 0.91). Through qualitative methods, items were improved until saturation was achieved. The tool consists of 6 domains and 38 questions. The 6 domains are: 1) support network; 2) access; 3) goals; 4) preferences; 5) feedback and tracking; and 6) barriers. There are 35 categorical questions and 3 open-ended items. Conclusions Using an iterative approach, the development and evaluation of the PEQ demonstrated high item-content validity for assessing the facilitators, barriers, and preferences to exercise in people with osteoporosis. Upon further validation it is expected that this measure might be used to develop more client-centered exercise programs, and potentially improve adherence.

Objective: To perform a systematic review and meta-analysis of randomized controlled trials on the efficacy of workplace-based interventions to prevent or treat shoulder pain. Data sources: A systematic review of 4 databases was performed up to January 2016. Study selection: Randomized controlled trials were included if the intervention under study was a workplace-based intervention performed to prevent or reduce shoulder pain and disability in workers. Data extraction: The methodological quality of the studies was evaluated and meta-analyses were conducted. Pooled mean differences and risk ratios were calculated. Data synthesis: Data from 4 studies on strengthening exercises performed in the workplace for workers with shoulder pain (n = 368) were pooled. A statistically significant reduction in pain intensity was observed compared with different control interventions (mean differences (scale out of 10) 1.31 (95% confidence interval (95% CI) 0.86–1.76)). Pooled data from 5 studies on the efficacy of workstation modifications (n = 2,148) showed a statistically significant reduction in the prevalence of shoulder pain with a risk ratio of 1.88 (95% CI 1.20–2.96) compared with different control interventions. Conclusion: Low-grade evidence exists that a workplace exercise programme may reduce the intensity of shoulder pain, and that workstation modifications may reduce the prevalence of shoulder pain.

Abstract In this work we analyze GISAXS measurements of the structure factor of Si surfaces evolving during 1 keV Ar+ ion bombardment. Using newly-developed methods sensitive to the full range of experimentally-available wavenumbers q, we extract the linear amplification rate R(q) governing surface stability over a range of wavenumbers 4–5 times larger than has previously been obtained. Comparing with theoretical models also retaining full wavenumber-dependence, we find an excellent fit of the experimental data over the full range of irradiation angles and wavenumbers. Moreover, the fitted parameter values represent experimental evaluation of the magnitudes of most physical mechanisms currently believed to be important to the pattern-formation process. In all cases, the extracted values agree well with direct observations or atomistic simulations of the same quantities, suggesting that GISAXS analysis may allow more powerful comparison between experiment and theory than had previously been thought.

Abstract Background Previous evidence suggests self-management programs for people with chronic pain improve knowledge and self-efficacy, but result in small to negligible changes in function. The purpose of this multiple case studies design was to describe the unique responses of six participants to a new self-management program aimed at improving function, to detail each component of the program, and to explore potential explanations for the varied trajectories of each of the participants. Case Presentation Six participants who had been experiencing chronic pain for at least 5 years were included. All participants were enrolled 6 weeks of ChrOnic pain self-ManageMent support with pain science EducatioN and exercise (COMMENCE). Participants completed an assessment at baseline, 7 weeks (1-week follow-up), and 18 weeks (12-week follow-up). Each participant had a unique initial presentation and goals. Assessments included: function as measured by the Short Musculoskeletal Function Assessment – Dysfunction Index, how much participants are bothered by functional difficulties, pain intensity, fatigue, pain interference, cognitive and psychological factors associated with pain and disability, pain neurophysiology, self-efficacy, satisfaction, and perceived change. The self-management program was 6-weeks in length, consisting of one individual visit and one group visit per week. The program incorporated three novel elements not commonly included in self-management programs: pain neurophysiology education, individualized exercises determined by the participants’ goals, and additional cognitive behavioural approaches. Participants were all satisfied with self-management support received. Change in function was variable ranging from 59% improvement to 17% decline. Two potential explanations for variances in response, attendance and social context, are discussed. Several challenges were identified by participants as barriers to attendance. Conclusions A primary care self-management intervention including pain education and individualized exercise has potential to improve function for some people with chronic pain, although strategies to improve adherence and reduce barriers to participation may be needed to optimize the impact.

Background: Missed medical appointments decrease continuity of medical care, waste resources, and may affect health outcomes. We examined the factors associated with missed children’s supervision visits in Eastern Brooklyn, NY, USA. Methods: We surveyed guardians whose children received routine medical care at four pediatric clinics. Participants filled out a questionnaire that queried: demographics, food security, recent relocation, parental support of healthy behaviors, and length of knowing provider. Preexisting disease(s) and missed visits were retrieved from medical records. Regression analyses were used to determine factors that were associated with missing medical appointments. Results: Among 213 families, 33% faced food insecurity and 16.4% reported moving within the past 12 months. Forty percent of children missed at least 1 visit. Food insecurity (adjusted odds ratio [aOR] 2.3, 95% confidence interval [CI 1.0% to 5.2%) and recent relocation (aOR 1.8, 95% CI 1.1-3.4 were associated with missed health supervision visits, whereas greater parental healthy behaviors (aOR 0.5, 95% CI 0.3-0.9) and longer length of knowing provider (aOR 0.8, 95% CI 0.7-1.0) were associated with fewer missed appointments. Conclusion: This study indicates that social inequity may contribute to poor adherence to medical appointments through multiple mechanisms, including food insecurity, lack of social stability, and parental health behaviors. Multidimensional proactive prevention, and reactive tolerance should be considered as opportunities to mitigate the impact of social inequity on health outcomes.

Objectives The purpose of this systematic review is to identify and synthesise studies evaluating performance-based functional outcome measures designed to evaluate the functional abilities of patients with neck pain.Design Systematic review.Data sources A literature search using PubMed, Scopus, CINAHL, EMBASE, COCHRANE, Google Scholar and a citation mapping strategy was conducted until July 2019.Eligibility criteria More than half of the study’s patient population had neck pain or a musculoskeletal neck disorder and completed a functional-based test. Clinimetric properties of at least one performance-based functional tests were reported. Both traumatic and non-traumatic origins of neck pain were considered.Data extraction and synthesis Relevant data were then extracted from selected articles using an extraction guide. Selected articles were appraised using the Quality Appraisal for Clinical Measurement Research Reports Evaluation Form (QACMRR).Results The search obtained 12 articles which reported on four outcome measures (functional capacity evaluations (FCE), Baltimore Therapeutic Equipment Work Simulator II (BTEWS II), Functional Impairment Test-Hand and Neck/Shoulder/Arm (FIT-HaNSA)) and a physiotherapy test package, to assess the functional abilities in patients with mechanical neck pain. Of the selected papers: one reports content validity, five construct validity, four reliability, one sensitivity to change and one both reliability and construct validity. QACMRR scores ranged from 68% to 95%.Conclusions This review found very good quality evidence that the FIT-HaNSA has excellent inter and intra-rater reliability and very weak to weak convergent validity. Excellent quality evidence of fair test-retest reliability, weak convergent validity and very weak known groups validity for the BTEWS II test was found. Good to excellent quality evidence exists that an FCE battery has poor to excellent reliability and very weak to strong validity. Good to excellent quality of weak to strong validity and trivial to strong effect sizes were found for a physiotherapy test package.Prospero registration number CRD42018112358

Objective The purpose of this systematic review was to critically appraise and synthesise the psychometric properties of Global Rating of Change (GROC) scales for assessment of patients with neck pain.Design Systematic review.Data sources A search was performed in four databases (MEDLINE, EMBASE, CINAHL, SCOPUS) until February 2019.Data extraction and synthesis Eligible articles were appraised using Consensus-based Standards for the selection of health Measurement Instruments checklist and the Quality Appraisal for Clinical Measurement Research Reports Evaluation Form.Results The search obtained 16 eligible studies and included in total 1533 patients with neck pain. Test–retest reliability of global perceived effect (GPE) was very high (intraclass correlation coefficient=0.80 to 0.92) for patients with whiplash. Pooled data of Pearson’s r indicated that GROC scores were moderately correlated with neck disability change scores (0.53, 95% CI: 0.47 to 0.59). Pooled data of Spearman’s correlations indicated that GROC scores were moderately correlated with neck disability change scores (0.56, 95% CI: 0.41 to 0.68).Conclusions This study found excellent quality evidence of very good-to-excellent test–retest reliability of GPE for patients with whiplash-associated disorders. Evidence from very good-to-excellent quality studies found that GROC scores are moderately correlated to an external criterion patient-reported outcome measure evaluated pre-post treatment in patients with neck pain. No studies were found that addressed the optimal form of GROC scales for patients with neck disorders or compared the GROC to other options for single-item global assessment.PROSPERO registration number CRD42018117874.

The 4-H Citizenship Project offers the opportunity to help 4-H members relate all of their 4-H projects and experiences to the world around them. The 4-H Citizenship manuals will serve as a guide for 4-H Citizenship experiences. To be truly meaningful to the real-life needs and interests of your group, the contribution of volunteer leaders is essential. Each person, neighborhood, and community has individual needs that you can help your group identify. This 23-page major revision of Unit VI covers the “My Government” project. Written by John Rutledge, Joy C. Jordan, and Dale Pracht and published by the UF/IFAS Extension 4-H Youth Development program. https://edis.ifas.ufl.edu/4h020