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This study examined students' perceptions of interprofessional multicultural learning activities used to develop cultural competence with humility (CCH). Limited research exists on student perceptions of learning activities for CCH in entry-level occupational therapy educational programs. This exploratory, mixed methods study used an anonymous online survey, the "Learning Activities Survey (LAS)," to collect student quantitative ratings and qualitative feedback about CCH learning activities and their experience within the "Counselors and Occupational Therapists Professionally Engaged in the Community (COPE)" program. A deductive thematic approach was used by two investigators for qualitative analyses of "COPE" learning activities by alignment in four a priori CCH constructs: cultural awareness, cultural knowledge, cultural skills, and cultural desire. Consensus was gained through discussion. Nineteen of 29 (65.5%) students completed the survey. The mean score on the LAS for 6 of 12 activities (50%) was at least "Moderately important" (mean [greater than or equal to] 3.0) to student learning. Twelve of 19 students (63%) rated 11 of 12 learning activities as Moderately important (mean [greater than or equal to] 3.0). Qualitatively, cognitive knowledge was the strongest reported CCH learning construct within the "COPE" program with a frequency of 32. The combined quantitative and qualitative responses indicated the learning activities positively influenced students' learning of CCH. This study may inform occupational therapy curricular activities that satisfy accreditation requirements and expectations of the profession to meet the cultural needs of society. It also provides support for revisions to occupational therapy educational program standards to better align with recent literature.

Background Interest in alternative sources of tubers and legumes has increased due to the search for raw materials with bioactive antioxidant compounds. The objective of this study was to characterize taro (TF) and sacha inchi (Plukenetia volubilis) flours obtained by the wet (SIF-WM) and defatted (SIF-DM) methods, as alternatives for the formulation of functional foods. Methods Proximal tests were conducted to determine basic chemical composition, quantification of free polyphenols, antioxidant activity using the ABTS* radical method (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) with Trolox as a standard, and rheological analyses, including pasting curves, flow profiles, and viscoelastic properties. Microbiological characterization of the flours was also performed. Results The highest protein content was found in sacha inchi flour obtained by the defatted method (72.62%), while carbohydrates were the main component in taro flour (85.4%). In terms of antioxidant activity, taro flour showed higher values of 2.71 µmol ET/g and 7.47 mg EAG/g. Rheological analysis showed that adding taro flour increased the viscosity peak and reduced breakdown, improving gel stability. Staphylococcus aureus and Salmonella spp. were detected in taro flour. Conclusions Taro and sacha inchi flours have great potential for the development of functional products like protein snacks, with good expansion due to taro starch and are naturally gluten-free, making them suitable for people with celiac disease.

Conjoined twins are very rare and some obstetricians may go through their career without ever managing a case. This case describes a thoraco-omphalopagus whereby the twins were joined at the chest and abdomen. Management of conjoined twins largely depends on the degree of conjoining and the availability of resources. In this case, the severity of the conjoining and lack of specialized resources resulted in managing via termination of the pregnancy. This is the first published case of conjoined twins from Trinidad and Tobago. The aim of this case report is to share our findings and management in a setting with limited resources.

Background Interest in alternative sources of tubers and legumes has increased in recent years because of the constant search for raw materials that provide bioactive compounds with antioxidant potential benefits for consumers. The functionality of new raw materials is sought through physical and/or chemical modifications to develop and innovate new foods. The objective of this study was to characterize taro (TF) (Colocasia esculenta) and sacha inchi (Plukenetia volubilis) flours, obtained by the wet (SIF-WM) and defatted method (SIF-DM), as an alternative for the formulation of new functional foods. Methods The free polyphenols of the different mixtures were analyzed, and the antioxidant properties of the extracts obtained were measured using ABTS.* (2,2′-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid). The ABTS radical method, which reacts with the phenolic compounds of the food matrix, using Trolox as a standard. The blends were subjected to pasting analysis, flow profile tests, determination of viscoelastic properties (temperature sweep). Characterization of common microorganisms in these foods was performed. Results The highest protein value was obtained in the sacha inchi flour obtained by the defatted method (72.62%). The majority of components in taro were carbohydrates (85.4%). About antioxidant and determination of free polyphenols, taro flour obtained values of 2.71 μmol ET/g and 7.47 mg EAG/g, higher than sacha inchi flours. In the rheological analysis (pasting properties, flow profile, and viscoelasticity), we observed that adding taro flour in different mixtures increases the viscosity peak and a lower breakdown, while there was an increase in setback. Except for defatted sacha flour, the others presented a flow index >1 before heating, showing a dilatant fluid behavior. The presence of taro flour improves gel formation and stability. Staphylococcus aureus and Salmonella were present in the taro flour. Conclusions The flours analyzed represent a raw material with great potential for the development of products such as protein snacks due to the contribution of sacha inchi, with good expansion due to taro starch, and naturally gluten-free for people with celiac disease.

Objectives This study aims to investigate the cost-effectiveness of individually tailored self-management support, delivered via the artificial intelligence-based selfBACK app, as an add-on to usual care for people with low back pain (LBP).Design Secondary health-economic analysis of the selfBACK randomised controlled trial (RCT) with a 9-month follow-up conducted from a Danish national healthcare perspective (primary scenario) and a societal perspective limited to long-term productivity in the form of long-term absenteeism (secondary scenario).Setting Primary care and an outpatient spine clinic in Denmark.Participants A subset of Danish participants in the selfBACK RCT, including 297 adults with LBP randomised to the intervention (n=148) or the control group (n=149).Interventions App-delivered evidence-based, individually tailored self-management support as an add-on to usual care compared with usual care alone among people with LBP.Outcome measures Costs of healthcare usage and productivity loss, quality-adjusted life-years (QALYs) based on the EuroQol-5L Dimension Questionnaire, meaningful changes in LBP-related disability measured by the Roland-Morris Disability Questionnaire (RMDQ) and the Pain Self-Efficacy Questionnaire (PSEQ), costs (healthcare and productivity loss measured in Euro) and incremental cost-effectiveness ratios (ICERs).Results The incremental costs were higher for the selfBACK intervention (mean difference €230 (95% CI −136 to 595)), where ICERs showed an increase in costs of €7336 per QALY gained in the intervention group, and €1302 and €1634 for an additional person with minimal important change on the PSEQ and RMDQ score, respectively. At a cost-effectiveness threshold value of €23250, the selfBACK intervention has a 98% probability of being cost-effective. Analysis of productivity loss was very sensitive, which creates uncertainty about the results from a societal perspective limited to long-term productivity.Conclusions From a healthcare perspective, the selfBACK intervention is likely to represent a cost-effective treatment for people with LBP. However, including productivity loss introduces uncertainty to the results.Trial registration number NCT03798288.

BackgroundmHealth has increasingly been touted as having the potential to help Sub-Saharan Africa achieve their health-related sustainable development goals by reducing maternal mortality rates. Such interventions are implemented as one-way or two-way systems where maternal clients receive pregnancy related information via SMS. While such technologies often view the users (the maternal health client) as having agency to adopt, we know from pregnancy literature that the pregnancy experience in Africa and other developing countries is often more collective. In addition to the maternal health client, other members of the community have high stakes in the pregnancy, and this often affects maternal healthcare-seeking behavior.ObjectiveThe aim of this paper, therefore, is to understand the pathways through which these other members of the community affect mHealth use.MethodsThe study used a qualitative approach and a case study research design. We analyzed two mHealth cases from Kenya and Malawi. In the Kenyan case, maternal health clients had mobile phones to receive pregnancy-related messages, while in the Malawi case, maternal health clients did not have mobile phones. Data were collected through interviews and focus group discussions. The study used an inductive thematic analysis to analyze the data.ResultsThe findings show that maternal stakeholders form a community of purpose (CoP) that plays a crucial role in the implementation, uptake, and use of mHealth. The CoP influences maternal health clients through a diverse range of mechanisms ranging from sensitization, bridging the digital literacy gap and legitimization of the intervention. The nature of influence is largely dependent on the contextual socio-cultural nuances.ConclusionOur results provide useful insights to mHealth implementers to know how best to leverage the CoP for better mHealth uptake and usage. For example, engaging healthcare providers could champion adoption and use, while engaging other family-related stakeholders will ensure better usage and compliance, encourage behavior change, and reduce mHealth attrition.

Objective Older adults constitute a heterogeneous group, and the focus of the individual physical exercise is often subject to the reasoning and experience of health professionals or exercise physiologists who prescribe them. Thus, this is the first effort to explicitly conceptualise the planning of individualised physical exercise training (IPET) for older adults in an outpatient setting and investigate individual exercise preferences.Design The concept of IPET was developed by researchers, exercise physiologists and health professionals from a real-life outpatient setting using an iterative approach. Health indicators assessing aerobic capacity, strength, balance and musculoskeletal pain/discomfort sites form the basis of physical exercise recommendations. A cross-sectional study was conducted to assess the basis of implementing IPET.Setting Outpatient setting.Participants We included 115 older adults (70 females) from an outpatient setting with a median age of 74 years.Outcome measures Health indicators assessing aerobic capacity, strength, balance and musculoskeletal pain/discomfort sites were collected and informed the concept of IPET that structures exercise programmes based on the individual citizen’s needs and physical exercise preferences. Exceeding a health indicator cut-point results in exercise content mitigating the risk associated with the health indicator.Results We included 115 older adults (70 females) from an outpatient setting median age of 74 years. Approximately two-thirds of participants exceeded at least one health indicator cut-point for aerobic training. One-third of the participants exceeded the cut-point for upper extremity strength, and almost all participants >99% exceeded the cut-point for lower extremity strength. Approximately two-thirds of the participants exceeded the cut-point for functional/balance training. The most prevalent site of musculoskeletal pain was the lower extremities. Eight of 20 training combinations were used, clustering the 115 participants primarily in three main training combinations.Discussion This study shows that older adults vary in physical functioning, indicating that exercise preferences and rehabilitation needs are individual.Trial registration number NCT04862481.

Citizen Science is a powerful tool for biodiversity research, as it facilitates data recording at large scales that would otherwise be impossible to cover by standard academic research. Despite its benefits, the accuracy of citizen science data remains a subject of concern among scientists, with varying results reported so far. Neither citizen science data nor academic records are immune to biases, which can significantly impact the quality and reliability of observations. Here, using insects in the Iberian Peninsula as a case study, we compare data collected by participatory platforms to those obtained through academic research projects, and assess their taxonomic, spatial, temporal, and environmental biases. Results show a prominent taxonomic bias in both academic and citizen science data, with certain insect orders receiving more attention than others. These taxonomic biases are conserved between different participatory platforms, as well as between groups of users with different levels of contribution performance. The biases captured by leading contributors in participatory platforms mirrored those of sporadic users and academic data. Citizen science data had higher spatial coverage and less spatial clustering than academic data, showing also clearer trends in temporal seasonality. Environmental coverage over time was more stable in citizen science than in academic records. User behaviour, preference, taxonomical expertise, data collection methodologies and external factors may contribute to these biases. This study shows the multifaceted nature of biases present in academic records and citizen science platforms. The insights gained from this analysis emphasize the need for careful consideration of these biases when making use of biodiversity data from different sources. Combining academic and citizen science data enhances our understanding of biodiversity, as their integration offers a more comprehensive perspective than relying solely on either dataset alone, especially since biases in these two types of data are not always the same.

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health.

AbstractObjective The primary objectives of this study were to 1) investigate the internal consistency 2) and construct validity of the Short Musculoskeletal Function Assessment Questionnaire (SMFA) in older adults commencing physical rehabilitation in an outpatient setting.Methods This cross-sectional study recruited older adults who had commenced physical rehabilitation in an outpatient setting. The SMFA consists of two indices: 1) dysfunction capturing the impact of musculoskeletal disorders on physical limitations, and 2) bothering capturing how the individual is emotionally affected by their disorder. SMFA holds four categories: ‘mobility’, ‘daily activities’, ‘emotional status’, and ‘function of the arm and hand’. Participants answered the SMFA alongside other patient-reported questionnaires (such as the 36-Item Short Form Survey, SF-36) and similar) and objectively measured muscle strength for the upper and lower body and functional capacity.Results We included 115 older adults with a median age of 74 years (IQR 9). Adequate internal consistency was seen with Cronbach’s alpha values of 0.90–0.94 for the SMFA indices and 0.77–0.91 for the SMFA categories. The strongest correlations between the SMFA indices were observed with the SF-36 physical component summary (SMFA-Dysfunction r = 0.74, p

To succeed in Canadian health professions, university education programs students must initially meet a variety of program-specific and English-language admission requirements. For non-native English-speaking (NNES) students, a major challenge can be the demonstration of profession-specific academic literacy and, in particular, adequate language competency prior to admission and throughout the program. Despite the increased numbers in the adult NNES student population in Canada, the current academic literacy requirements within these programs have received minimal research focus. This study explores the congruency of program requirements and learning supports within three major health professions programs across six Canadian universities. The data analyzed for this qualitative study include program documents on publicly accessible websites and a focused literature review. Findings suggest that in medicine, nursing, and pharmacy programs, discipline-specific academic literacy manifests itself in a wide variety of specialized written genres, ranging from reflections to theoretical analysis. Academic literacy is essential to the socialization of new students into these specialized programs and into the professions. Suggestions are offered to enhance universities' support of the development of academic literacy of NNES students.

Abstract Immunity with SARS-CoV-2 infection during the acute phase is not sufficiently well understood to differentiate mild from severe cases and identify prognostic markers. We evaluated the immune response profile using a total of 71 biomarkers in sera from patients with SARS-CoV-2 infection, confirmed by RT-PCR and controls. We correlated biological marker levels with negative control (C) asymptomatic (A), nonhospitalized (mild cases-M), and hospitalized (severe cases-S) groups. Among angiogenesis markers, we identified biomarkers that were more frequently elevated in severe cases when compared to the other groups (C, A, and M). Among cardiovascular diseases, there were biomarkers with differences between the groups, with D-dimer, GDF-15, and sICAM-1 higher in the S group. The levels of the biomarkers Myoglobin and P-Selectin were lower among patients in group M compared to those in groups S and A. Important differences in cytokines and chemokines according to the clinical course were identified. Severe cases presented altered levels when compared to group C. This study helps to characterize biological markers related to angiogenesis, growth factors, heart disease, and cytokine/chemokine production in individuals infected with SARS-CoV-2, offering prognostic signatures and a basis for understanding the biological factors in disease severity.

Abstract Background selfBACK, an artificial intelligence (AI)-based app delivering evidence-based tailored self-management support to people with low back pain (LBP), has been shown to reduce LBP-related disability when added to usual care. LBP commonly co-occurs with multimorbidity (≥ 2 long-term conditions) or pain at other musculoskeletal sites, so this study explores if these factors modify the effect of the selfBACK app or influence outcome trajectories over time. Methods Secondary analysis of a randomized controlled trial with 9-month follow-up. Primary outcome is as follows: LBP-related disability (Roland Morris Disability Questionnaire, RMDQ). Secondary outcomes are as follows: stress/depression/illness perception/self-efficacy/general health/quality of life/physical activity/global perceived effect. We used linear mixed models for continuous outcomes and logistic generalized estimating equation for binary outcomes. Analyses were stratified to assess effect modification, whereas control (n = 229) and intervention (n = 232) groups were pooled in analyses of outcome trajectories. Results Baseline multimorbidity and co-occurring musculoskeletal pain sites did not modify the effect of the selfBACK app. The effect was somewhat stronger in people with multimorbidity than among those with LBP only (difference in RMDQ due to interaction, − 0.9[95 % CI − 2.5 to 0.6]). Participants with a greater number of long-term conditions and more co-occurring musculoskeletal pain had higher levels of baseline disability (RMDQ 11.3 for ≥ 2 long-term conditions vs 9.5 for LBP only; 11.3 for ≥ 4 musculoskeletal pain sites vs 10.2 for ≤ 1 additional musculoskeletal pain site); along with higher baseline scores for stress/depression/illness perception and poorer pain self-efficacy/general health ratings. In the pooled sample, LBP-related disability improved slightly less over time for people with ≥ 2 long-term conditions additional to LBP compared to no multimorbidity and for those with ≥4 co-occurring musculoskeletal pain sites compared to ≤ 1 additional musculoskeletal pain site (difference in mean change at 9 months = 1.5 and 2.2, respectively). All groups reported little improvement in secondary outcomes over time. Conclusions Multimorbidity or co-occurring musculoskeletal pain does not modify the effect of the selfBACK app on LBP-related disability or other secondary outcomes. Although people with these health problems have worse scores both at baseline and 9 months, the AI-based selfBACK app appears to be helpful for those with multimorbidity or co-occurring musculoskeletal pain. Trial registration NCT03798288 . Date of registration: 9 January 2019

Abstract Sirenomelia is a rare type of dysmelia characterized by partial or complete fusion of the legs. We present a 31-year-old P1+0 who first presented to our antenatal clinic at 17+1 weeks gestational age. An ultrasonographic examination done showed a single foetus with a structurally normal head, chest, and upper limbs. The vertebrae of the lumbosacral spine appeared disorganised. The lower limbs appeared to be fused throughout its length. The ultrasonographic findings were consistent with Sirenomelia-Type 3. Although this condition is likely to have been encountered before in Trinidad and Tobago, this would be the first documented case.

BackgroundStudies indicate that physical activity during leisure and work have opposite associations with cardiovascular disease (CVD) risk factors, referred to as the physical activity health paradox. We investigated how sedentary behaviour and physical activity types during leisure and work are associated with systolic blood pressure (SBP), waist circumference (WC), and low-density lipoprotein cholesterol (LDL-C) in an adult general population sample using compositional data analysis.MethodsParticipants wore accelerometers for 7 days (right thigh and iliac crest; 24 h/day) and had their SBP, WC, and LDL-C measured. Accelerometer data was analysed using the software Acti4 to derive daily time spent in sedentary behaviour and physical activity types. The measure of association was quantified by reallocating time between sedentary behaviour and 1) walking, and 2) high-intensity physical activity (HIPA; sum of climbing stairs, running, cycling, and rowing), during both domains.ResultsIn total, 652 participants were included in the analyses (median wear time: 6 days, 23.8 h/day). During leisure, the results indicated that less sedentary behaviour and more walking or more HIPA was associated with lower SBP, while during work, the findings indicated an association with higher SBP. During both domains, the findings indicated that less sedentary behaviour and more HIPA was associated with a smaller WC and lower LDL-C. However, the findings indicated less sedentary behaviour and more walking to be associated with a larger WC and higher LDL-C, regardless of domain.ConclusionsDuring leisure, less sedentary behaviour and more walking or HIPA seems to be associated with a lower SBP, but, during work, it seems to be associated with a higher SBP. No consistent differences between domains were observed for WC and LDL-C. These findings highlight the importance of considering the physical activity health paradox, at least for some risk factors for CVD.

Production of proliferative follicle cells (FCs) and quiescent escort cells (ECs) by follicle stem cells (FSCs) in adult Drosophila ovaries is regulated by niche signals from anterior (cap cells, ECs) and posterior (polar FCs) sources. Here we show that ECs, FSCs, and FCs develop from common pupal precursors, with different fates acquired by progressive separation of cells along the AP axis and a graded decline in anterior cell proliferation. ECs, FSCs, and most FCs derive from intermingled cell (IC) precursors interspersed with germline cells. Precursors also accumulate posterior to ICs before engulfing a naked germline cyst projected out of the germarium to form the first egg chamber and posterior polar FC signaling center. Thus, stem and niche cells develop in appropriate numbers and spatial organization through regulated proliferative expansion together with progressive establishment of spatial signaling cues that guide adult cell behavior, rather than through rigid early specification events.

Objective To test if patients recovering from COVID-19 are at increased risk of mental morbidities and to what extent such risk is exacerbated by illness severity.Design Population-based cross-sectional study.Setting Iceland.Participants A total of 22 861 individuals were recruited through invitations to existing nationwide cohorts and a social media campaign from 24 April to 22 July 2020, of which 373 were patients recovering from COVID-19.Main outcome measures Symptoms of depression (Patient Health Questionnaire), anxiety (General Anxiety Disorder Scale) and posttraumatic stress disorder (PTSD; modified Primary Care PTSD Screen for DSM-5) above screening thresholds. Adjusting for multiple covariates and comorbidities, multivariable Poisson regression was used to assess the association between COVID-19 severity and mental morbidities.Results Compared with individuals without a diagnosis of COVID-19, patients recovering from COVID-19 had increased risk of depression (22.1% vs 16.2%; adjusted relative risk (aRR) 1.48, 95% CI 1.20 to 1.82) and PTSD (19.5% vs 15.6%; aRR 1.38, 95% CI 1.09 to 1.75) but not anxiety (13.1% vs 11.3%; aRR 1.24, 95% CI 0.93 to 1.64). Elevated relative risks were limited to patients recovering from COVID-19 that were 40 years or older and were particularly high among individuals with university education. Among patients recovering from COVID-19, symptoms of depression were particularly common among those in the highest, compared with the lowest tertile of influenza-like symptom burden (47.1% vs 5.8%; aRR 6.42, 95% CI 2.77 to 14.87), among patients confined to bed for 7 days or longer compared with those never confined to bed (33.3% vs 10.9%; aRR 3.67, 95% CI 1.97 to 6.86) and among patients hospitalised for COVID-19 compared with those never admitted to hospital (48.1% vs 19.9%; aRR 2.72, 95% CI 1.67 to 4.44).Conclusions Severe disease course is associated with increased risk of depression and PTSD among patients recovering from COVID-19.

Knowledge of why parents use complementary health approaches (CHA) for children with autism spectrum disorder (ASD) is limited. We conducted a mixed methods study to better understand factors influencing parents' decision to use CHA for ASD. Parent-reported data about CHA use were collected on a probability sample of 352 young children with ASD in Denver, Colorado; Los Angeles, California; or Portland, Oregon. Follow-back interviews were conducted with 31 parents. CHA use was negatively associated with older child age and positively associated with parents' belief ASD has major consequences, living in Portland or Denver, and medication use. Nine themes help explain these results. Study findings may have utility for healthcare providers working with children with ASD and their families regarding CHA.

Chiari Malformation Type 1 (CM-1) is characterized by herniation of the cerebellar tonsils below the foramen magnum and the presence of headaches and other neurologic symptoms. Cranial bone constriction is suspected to be the most common biologic mechanism leading to CM-1. However, other mechanisms may also contribute, particularly in the presence of connective tissue disorders (CTDs), such as Ehlers Danlos Syndrome (EDS). Accumulating data suggest CM-1 with connective tissue disorders (CTD+) may have a different patho-mechanism and different genetic risk factors than CM-1 without CTDs (CTD-). To identify CM-1 genetic risk variants, we performed whole exome sequencing on a single large, multiplex family from Spain and targeted sequencing on a cohort of 186 unrelated adult, Caucasian females with CM-1. Targeted sequencing captured the coding regions of 21 CM-1 and EDS candidate genes, including two genes identified in the Spanish family. Using gene burden analysis, we compared the frequency of rare, functional variants detected in CM-1 cases versus publically available ethnically-matched controls from gnomAD. A secondary analysis compared the presence of rare variants in these genes between CTD+ and CTD- CM-1 cases. In the Spanish family, rare variants co-segregated with CM-1 in COL6A5, ADGRB3 and DST. A variant in COL7A1 was present in affected and unaffected family members. In the targeted sequencing analysis, rare variants in six genes (COL7A1, COL5A2, COL6A5, COL1A2, VEGFB, FLT1) were significantly more frequent in CM-1 cases compared to public controls. In total, 47% of CM-1 cases presented with rare variants in at least one of the four significant collagen genes and 10% of cases harbored variants in multiple significant collagen genes. Moreover, 26% of CM-1 cases presented with rare variants in the COL6A5 gene. We also identified two genes (COL7A1, COL3A1) for which the burden of rare variants differed significantly between CTD+ and CTD- CM-1 cases. A higher percentage of CTD+ patients had variants in COL7A1 compared to CTD+ patients, while CTD+ patients had fewer rare variants in COL3A1 than did CTD- patients. In summary, rare variants in several collagen genes are particularly frequent in CM-1 cases and those in COL6A5 co-segregated with CM-1 in a Spanish multiplex family. COL6A5 has been previously associated with musculoskeletal phenotypes, but this is the first association with CM-1. Our findings underscore the contribution of rare genetic variants in collagen genes to CM-1, and suggest that CM-1 in the presence and absence of CTD symptoms is driven by different genes.

Introduction Successful rehabilitation of the growing number of older citizens receiving healthcare services can lead to preservation of functional independence and improvement in quality of life. Adequate intake of dietary protein and physical training are key factors in counteracting the age-related decline in strength performance and physical function. However, during rehabilitation, many older people/persons have insufficient protein intake, and difficulties in performing exercise training with sufficient intensity and volume. The primary aim of this trial is to investigate if individualised physical exercise training programmes combined with increased protein intake (IPET+P) can improve measures on all International Classification of Functioning, Disability and Health levels, such as strength, gait speed and health-related quality of life, when compared with care as usual in municipality-based rehabilitation alone (usual care, UC) or care as usual in combination with increased protein intake (UC+P). Further, the trial investigates whether UC+P will potentiate more significant improvements in outcome measures than UC.Methods and analysis The trial is a three-armed multicentre, block-randomised controlled trial consisting of a 12-week intervention period with a 1-year follow-up. Citizens above 65 years referred to rehabilitation in the municipality without restricting comorbidities are eligible. Participants are randomised to either a UC group, a UC group with protein supplementation receiving 27.5 g protein/day (UC+P), or an IPET+P supplementation of 27.5 g protein/day. The Short Musculoskeletal Function Assessment questionnaire is the primary outcome.Ethics and dissemination Approvals from The Ethics Committee in Region Zealand, Denmark (SJ-758), and the General Data Protection Regulation at the University of Southern Denmark, Odense (10.330) have been obtained.Trial registration number NCT04091308

Candida auris is an emerging yeast that causes healthcare-associated infections. It can be misidentified by laboratories and often is resistant to antifungal medications. We describe an outbreak of C. auris infections in healthcare facilities in New York City, New York, USA. The investigation included laboratory surveillance, record reviews, site visits, contact tracing with cultures, and environmental sampling. We identified 51 clinical case-patients and 61 screening case-patients. Epidemiologic links indicated a large, interconnected web of affected healthcare facilities throughout New York City. Of the 51 clinical case-patients, 23 (45%) died within 90 days and isolates were resistant to fluconazole for 50 (98%). Of screening cultures performed for 572 persons (1,136 total cultures), results were C. auris positive for 61 (11%) persons. Environmental cultures were positive for samples from 15 of 20 facilities. Colonization was frequently identified during contact investigations; environmental contamination was also common.

There is still much to learn about the support required by postgraduate research students, across academic disciplines, to facilitate successful completion of a research degree. The primary aim of this study was to explore postgraduate medical science research students' perceptions of academic and mentoring support at different stages during their degree programme. A second aim was to explore the feasibility and acceptability of peer mentoring as a strategy to enhance student support in this population. A mixed method study design was used. Students first completed an online questionnaire, which was then supplemented with focus group discussion to explore emergent findings in greater depth. The main results indicated that the nature and quality of academic supervision support have a significant influence on research student training and development. 'Functional' and 'relationship development' concepts of supervisory styles were highlighted as important aspects to perceived support in this research population. The main facilitators to enhance academic support were effective communication, project planning and timely feedback. There was a high degree of acceptability for a peer mentoring programme as a complementary approach to enhance student support. Peer mentoring psychosocial functions such as friendship, counselling and career guidance were considered potentially beneficial to enhancing student support. Students also discussed peer coaching as central to their learning and research skill development. This work is a useful starting point to explore perceptions of research student support in the target population. Further work is required to develop strategies to enhance student support in academic practice.

The Human Genome Project was an enormous accomplishment, providing a foundation for countless explorations into the genetics and genomics of the human species. Yet for many years, the human genome reference sequence remained incomplete and lacked representation of human genetic diversity. Recently, two major advances have emerged to address these shortcomings: complete gap-free human genome sequences, such as the one developed by the Telomere-to-Telomere Consortium, and high-quality pangenomes, such as the one developed by the Human Pangenome Reference Consortium. Facilitated by advances in long-read DNA sequencing and genome assembly algorithms, complete human genome sequences resolve regions that have been historically difficult to sequence, including centromeres, telomeres, and segmental duplications. In parallel, pangenomes capture the extensive genetic diversity across populations worldwide. Together, these advances usher in a new era of genomics research, enhancing the accuracy of genomic analysis, paving the path for precision medicine, and contributing to deeper insights into human biology.

Abstract Intensively managed grasslands are dominated by highly productive grass-clover mixtures. Increasing crop diversity by inclusion of competitive forbs may enhance biomass production and sustainable biofuel production. Here we examined if one or all of three forbs (chicory, Cichorium intybus L.; caraway, Carum carvi L.; plantain, Plantago lanceolata L.) included in ryegrass-red clover mixtures enhanced above- and below-ground productivity, and assessed their biofuel potentials, based on a three-year experiment with and without fertilisation as cattle slurry. We determined herbage yield, standing root biomass, and estimated methane energy output and greenhouse gas (GHG) emissions per energy unit using life cycle assessment. Results showed that plantain-containing grass-clover mixtures significantly increased herbage yield, while chicory- or caraway-containing mixtures maintained similar yields to the grass-clover mixture. Standing root biomass of the grass-clover mixture was enhanced by inclusion of caraway and plantain, with that of plantain further enhanced by fertilisation. The highest methane energy output was achieved in plantain-containing grass-clover mixtures. All unfertilised mixtures achieved the 60% reduction in GHG emissions compared to fossil fuel, whereas all fertilised mixtures did not meet the 60% reduction target. These findings suggest that including competitive forbs such as plantain in grass-clover mixtures enhances productivity, supporting low-carbon footprint bioenergy production.

Widespread availability of antibiotics without prescription potentially facilitates overuse and contributes to selection pressure for antimicrobial resistant bacteria. Prior to this study, anecdotal observations in Guatemala identified corner stores as primary antibiotic dispensaries, where people purchase antibiotics without prescriptions. We carried out a cross sectional study to document the number and types of antibiotics available in corner stores, in four study areas in Guatemala. A total of 443 corner stores were surveyed, of which 295 (67%) sold antibiotics. The most commonly available antibiotics were amoxicillin, found in 246/295 (83%) stores, and tetracycline, found in 195/295 (66%) stores. Over the counter sales result from laissez-faire enforcement of antibiotic dispensing regulations in Guatemala combined with patient demand. This study serves as a baseline to document changes in the availability of antibiotics in informal establishments in light of new pharmacy regulations for antibiotic dispensing, which were adopted after this study was completed.

Objective Brain tumours are relatively rare but hold a significant place in cancer rehabilitation due to their pronounced disabling capacity to promote physical, cognitive and psychosocial sequelae. This small-scale qualitative study used coping and motivational theories to gain understanding and knowledge of patients’ experience of being diagnosed with a severe disease and of their view of a rehabilitation process.Design Qualitative interview study.Setting Odense University Hospital, Denmark.Informants Five patients (men, aged 30–79 years) with primary glioma who had participated in a rehabilitation intervention.Methods Semi-structured interviews were conducted. The phenomenological interpretive analysis was used to analyse the interviews.Results The analysis revealed three main themes: (1) coping with a new life situation, (2) motivating and maintaining elements and (3) experience of the benefit of the rehabilitation programme.Conclusion The study concluded that interviewed informants use problem-solving coping strategies, which make them more active in their health behaviour. However, passive and emotion-focused strategies related to confronting diagnosis may be used in some cases. The motivational aspect is multifaceted. Personal and interpersonal elements alongside a competitive setting are crucial to self-efficacy and benefit. The intervention’s impact on health-related quality of life also has the potential to increase patients’ resources to manage their situation.Trial registration number NCT02221986

As a learning model, apprenticeship is well known for its capacity to develop skills and vocational identities. It is also increasingly appealing for its potential to develop soft skills and enhance dispositions. This article focuses on the nature and role of apprenticeship and employers in developing dispositions and soft skills. It draws on a two-year New Zealand study of 41 apprentices in general practice medicine, carpentry, and engineering technician work, and their workplace mentors and teachers. The study theorised that apprentices' most significant learning is personally as well as professionally challenging, and can be understood in terms of "vocational thresholds"--portals to deeper capability in the field. This article argues that crossing vocational thresholds requires ongoing development of dispositions and soft skills, critically supported by workplace mentors and teachers. The article suggests that the situated nature of apprenticeship uniquely positions it to foster dispositions and soft skills, and that these are field-specific and learnable, rather than general, abstract and fixed.

Parent-child sexual health communication has been shown to protect against adolescent sexual risk-taking behavior. Parent knowledge of adolescent sexual experience can inform timing and content of conversations; however, little is known about factors associated with such knowledge. To investigate this question, parent-child dyads (N = 942) from a U.S. nationally-representative internet panel were surveyed in June 2012. Agreement between adolescent report of vaginal sex and parent's knowledge of such behavior was assessed. Multivariate regression was used to assess predictors of accurate parental knowledge of adolescent sex. Most parents (87%) reported knowledge of their adolescents' sexual experience. Parents with accurate knowledge of adolescent sexual experience were more likely to report at least one prior conversation with their child about sexual health (OR 2.35), have a daughter (OR 1.88), and have a child who expressed comfort discussing sexual health (OR 1.71). Results indicate that parental knowledge of adolescent sexual experience reflects more comfortable parent-child sexual health communication. Developing tools to improve adolescent comfort discussing sexuality may improve parent-child conversations about sexuality, contributing to efforts to increase safer sex practices among adolescents.

Vertical integration has been extensively implemented across medical school curricula but has not been widely attempted in the field of biochemistry. We describe a novel curricular innovation in which a near-peer learning model was used to implement vertical integration in our medical school biochemistry course. Senior medical students developed and facilitated a case-based small group session for first year biochemistry students. Students were surveyed before and after the session on their attitudes about biochemistry, as well as the effectiveness of the session. Prior to the session, the students believed biochemistry was more important to understanding the basic science of medicine than it was to understanding clinical medicine or becoming a good physician. The session improved students' attitudes about the importance of biochemistry in clinical medicine, and after the session they now believe that understanding biochemistry is equally important to the basic sciences as clinical medicine. Students would like more sessions and believe the senior student facilitators were knowledgeable and effective teachers. The facilitators believe they improved their teaching skills. This novel combination of near-peer learning and vertical integration in biochemistry provided great benefit to both first year and senior medical students, and can serve as a model for other institutions.

The engagement and retention of commencing students is a longstanding issue in higher education, particularly with the implementation of the widening student participation agenda. The early weeks of the first semester are especially critical to student engagement and early attrition. This study investigated the perceived early transition needs of three cohorts of commencing students in their first three weeks of university study in a Health Faculty. A short survey was developed based on a systematic understanding of student transition and supplemented by open-ended qualitative data. The results showed a stable, consistent pattern of early transition needs across the cohorts, with commencing students expressing most concern about accessing resources, balancing work, family and study commitments, establishing peer relationships, and understanding the requirements and standards for early assessment tasks, particularly group tasks. Findings are discussed in terms of implications for early co-curricular and curricular interventions to enhance early student engagement and retention.

El déficit de atención e hiperactividad (TDAH) es uno de los trastornos del comportamiento más frecuentes en pediatría, que genera conductas maladaptativas inconsistentes con la edad y el desarrollo del niño. Recientemente ha despertado gran interés la alta coexistencia de este con trastornos de sueño, al igual que una posible causa bidireccional entre las alteraciones de la arquitectura del sueño y los síntomas principales del TDAH. El objetivo de esta revisión es encontrar la asociación entre el TDAH y los trastornos del sueño en la población pediátrica, evaluando a profundidad los documentos, con el fin de encontrar nivel de evidencia, para ampliar a futuro la intervención sobre el TDAH y optimizar la calidad de vida de estos pacientes, a corto y largo plazos. Se realizó la búsqueda en Pubmed, Cochrane y Fabumed, escogiendo estudios en niños, con menos de 10 años de publicación, en inglés o español, con acceso completo. Se escogieron 52 estudios basándose en su calidad y nivel de evidencia.

Plant species diversity may benefit natural grassland productivity, but its effect in managed grassland systems is not well understood. A four-year multispecies grassland experiment was conducted to investigate the effect of species diversity-legumes and non-leguminous forbs-on productivity, persistence and sward quality under cutting or grazing regimes and with or without slurry application. Three mixtures were established- 3-mix: grass, red and white clover, 10-mix: 3-mix plus birdsfoot trefoil and six non-leguminous forbs, and 12-mix: 10-mix plus lucerne and festulolium. Species diversity increased sward production and yield persistence under cutting regime. The 12-mix had the highest yield from the second year onwards and no statistically significant yield reduction over four years, while annual yields in the 3-mix and 10-mix decreased significantly with increasing grassland age. The higher yield in the 12-mix was mainly due to the inclusion of high-yielding lucerne. The 10-mix and 12-mix had lower proportions of unsown species than the 3-mix, the difference being dependent on grassland age. Generally, the 3-mix had higher concentrations of in-vitro organic matter digestibility (IVOMD), neutral detergent fiber (NDF) and crude protein (CP), and a lower concentration of ash than the 10-mix and 12-mix. Slurry application increased annual yield production by 10% and changed the botanical composition, increasing the proportion of grass and decreasing the proportion of legumes. Compared to cutting, grazing increased forage production by 9% per cut on average and lowered legume and forb proportions in the mixtures, but yields did not differ among the three mixtures. Overall, our results suggest that species diversity increases sward productivity and persistence only under an ungrazed cutting regime. We conclude that increasing species diversity by selecting appropriate species with compatible management is key to achieving both high yields and high persistence in managed grasslands.

Rapid expansion in scientific knowledge, changes in medical practice, and greater demands from patients and society necessitate reform of the medical curriculum. In recognition of this, medical educators across the world have recommended the adoption of competence-based education. This is intended to increase the rigour and relevance of the curriculum, move students beyond a focus on the memorisation and regurgitation of scientific facts, and better enable them to understand scientific principles and apply them to the practice of medicine. Experience from 40 years' use of competence-based curricula across the world suggests that the uncritical application of this approach to the medical curriculum may not achieve its intended aims. There are valuable lessons to be learnt from the history of competence-based education. By taking on board these lessons, confronting the pitfalls of this approach, and devising new and creative solutions to the problems inherent in this methodology, medical educators can better achieve their aim of providing a strong foundation for the practice of medicine in the twenty-first century. It is only through such a strategy--rather than the uncritical adoption of this educational approach--that we will have real movement and progress both in competence-based education in general, and in its applications to medicine in particular.

OBJECTIVES:Occupational groups exposed to high occupational physical activity have an increased risk for cardiovascular disease (CVD). This may be explained by the high relative aerobic workload. Enhanced cardiorespiratory fitness reduces the relative aerobic workload. Thus, the aim was to evaluate the 12-months effects of worksite aerobic exercise on risk factors for CVD among cleaners. METHODS:One hundred and sixteen cleaners aged 18-65 years were randomized to a group performing aerobic exercise and a reference group receiving lectures. Outcomes were collected at baseline and after 12-months. A repeated measures 2×2 multi-adjusted mixed-model design was applied to compare the between-group differences using intention-to-treat analysis. RESULTS:Between-group differences (p

To establish the frequency of necrotizing funisitis in congenital syphilis, we conducted a prospective descriptive study of maternal syphilis in Bolivia by testing 1,559 women at delivery with rapid plasma reagin (RPR). We examined umbilical cords of 66 infants whose mothers had positive RPR and fluorescent treponemal antibody absorption tests. Histologic abnormalities were detected in 28 (42%) umbilical cords (seven [11%] had necrotizing funisitis with spirochetes; three [4%] had marked funisitis without necrosis; and 18 [27%] had mild funisitis), and 38 [58%] were normal. Of 22 umbilical cords of infants from mothers without syphilis (controls), only two (9%) showed mild funisitis; the others were normal. Testing umbilical cords by using immunohistochemistry is a research tool that can establish the frequency of funisitis due to Treponema pallidum infection.

BackgroundInternet-based cognitive behavioural therapy (iCBT) for generalized anxiety disorder (GAD) has been shown to be effective when guided by a clinician. The present study sought to replicate this finding, and determine whether support from a technician is as effective as guidance from a clinician.MethodRandomized controlled non-inferiority trial comparing three groups: Clinician-assisted vs. technician-assisted vs. delayed treatment. Community-based volunteers applied to the VirtualClinic (www.virtualclinic.org.au) research program and 150 participants with GAD were randomized. Participants in the clinician- and technician-assisted groups received access to an iCBT program for GAD comprising six online lessons, weekly homework assignments, and weekly supportive contact over a treatment period of 10 weeks. Participants in the clinician-assisted group also received access to a moderated online discussion forum. The main outcome measures were the Penn State Worry Questionnaire (PSWQ) and the Generalized Anxiety Disorder-7 Item (GAD-7). Completion rates were high, and both treatment groups reduced scores on the PSWQ (pConclusionsBoth clinician- and technician-assisted treatment resulted in large effect sizes and clinically significant improvements comparable to those associated with face-to-face treatment, while a delayed treatment/control group did not improve. These results provide support for large scale trials to determine the clinical effectiveness and acceptability of technician-assisted iCBT programs for GAD. This form of treatment has potential to increase the capacity of existing mental health services.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12609000563268.

BACKGROUND: Internet-based cognitive behavioural therapy (iCBT) for depression is effective when guided by a clinician, less so if unguided. QUESTION: Would guidance from a technician be as effective as guidance from a clinician? METHOD: Randomized controlled non-inferiority trial comparing three groups: Clinician-assisted vs. technician-assisted vs. delayed treatment. Community-based volunteers applied to the VirtualClinic (www.virtualclinic.org.au) research program, and 141 participants with major depressive disorder were randomized. Participants in the clinician- and technician-assisted groups received access to an iCBT program for depression comprising 6 online lessons, weekly homework assignments, and weekly supportive contact over a treatment period of 8 weeks. Participants in the clinician-assisted group also received access to a moderated online discussion forum. The main outcome measures were the Beck Depression Inventory (BDI-II) and the Patient Health QUESTIONnaire-9 Item (PHQ-9). Completion rates were high, and at post-treatment, both treatment groups reduced scores on the BDI-II (p

ResumenLa preparación durante el tratamiento endodóntico consiste en la correcta limpieza y conformación del sistema de conductos radiculares, y que conserve siempre su forma original. Al finalizar la preparación, se debe obtener un conducto con conicidad uniforme y con un tope apical, que permita un selle hermético al momento de la obturación. Se debe tener en cuenta la dificultad para lograr resultados satisfactorios sobre todo en conductos curvos y calcificados debido a la complejidad de éstos. Las técnicas implementadas y el instrumental adecuado para la preparación de conductos, han sido muchos con el fin de minimizar los errores durante la preparación. No obstante, ninguna técnica ni instrumental por sí solo resulta ideal en la prevención de estos errores; es necesario el cumplimiento de algunos principios básicos durante la preparación de estos conductos, tales como la correcta preparación coronal, el uso continuo de irrigantes y agentes quelantes, el mantenimiento de la permeabilidad, el limado anticurvatura y la doble conicidad. La incorrección de estos principios conlleva a errores, los cuales dificultan el éxito del tratamiento endodóntico. Los avances de la ciencia y el advenimiento de los instrumentos de níquel-titanio, han logrado facilitar el tratamiento de endodoncia, tanto que ya no es considerado como anteriormente se le atribuía que era un procedimiento difícil, lo importante predecir la orientación y anatomía del conducto antes de emplear técnicas o instrumentales, ya que un error en ellas nos llevará al fracaso del tratamiento. (DUAZARY 2011, 66 - 73)AbstractThe preparation for the endodontic treatment is proper cleaning and shaping the root canal system, and always keep its original shape. After the preparation, must be obtained through uniform and tapered with an apical stop, allowing a tight seal when the seal. It must take into account the difficulty of achieving satisfactory results especially in curved canals and calcified due to the complexity of these, the implemented techniques, and instrumentation suitable for the preparation of pipes have been many in order to minimize errors during preparation. But any technique or instrument itself ideal in preventing these errors, it is necessary to comply with some basic principles for the preparation of these channels, such as proper preparation coronal, the continued use of irrigants and chelating agents, maintenance of the permeability, filing anticurvatura and double taper. The incorrectness of these principles leads to errors which hinder the success of endodontic treatment. The progress of science and the advent of nickel-titanium instrument, it has been facilitating both root canal treatment is no longer considered previously attributed to him was a difficult procedure, the important thing to predict the orientation and anatomy through before using or instrumental techniques, since an error in them will lead to treatment failure.Keywords: development; calcification; root canal.

INTRODUCTION: Understanding the detailed control of human locomotion and balance can be improved, when individual motor units can be isolated and their firing rates followed in natural movement of large, fuctionally important muscles. For this reason the present study investigated the motor unit discharge rate (MUDR) in isometric and dynamic contractions of the soleus muscle. METHODS: Eleven males performed isometric (10-100% MVC) and dynamic (10-40% MVC) plantar flexions. Intramuscular EMG was measured from Soleus with bipolar wire-electrodes and decomposed with custom built "Daisy" software. RESULTS: The Soleus MUDR was significantly higher in concentric compared to isometric or eccentric contractions at all submaximal force levels (P

PurposeTo investigate if persons with high physical activity at work have the same benefits from leisure time physical activity as persons with sedentary work.MethodsIn the Copenhagen City Heart Study, a prospective cohort of 7,411 males and 8,916 females aged 25-66 years without known cardiovascular disease at entry in 1976-78, 1981-83, 1991-94, or 2001-03, the authors analyzed with sex-stratified multivariate Cox proportional hazards regression the association between leisure time physical activity and cardiovascular and all-cause mortality among individuals with different levels of occupational physical activity.ResultsDuring a median follow-up of 22.4 years, 4,003 individuals died from cardiovascular disease and 8,935 from all-causes. Irrespective of level of occupational physical activity, a consistently lower risk with increasing leisure time physical activity was found for both cardiovascular and all-cause mortality among both men and women. Compared to low leisure time physical activity, the survival benefit ranged from 1.5-3.6 years for moderate and 2.6-4.7 years for high leisure time physical activity among the different levels of occupational physical activity.ConclusionPublic campaigns and initiatives for increasing physical activity in the working population should target everybody, irrespective of physical activity at work.

Chiari Type I Malformation (CMI) is characterized by displacement of the cerebellar tonsils below the base of the skull, resulting in significant neurologic morbidity. Although multiple lines of evidence support a genetic contribution to disease, no genes have been identified. We therefore conducted the largest whole genome linkage screen to date using 367 individuals from 66 families with at least two individuals presenting with nonsyndromic CMI with or without syringomyelia. Initial findings across all 66 families showed minimal evidence for linkage due to suspected genetic heterogeneity. In order to improve power to localize susceptibility genes, stratified linkage analyses were performed using clinical criteria to differentiate families based on etiologic factors. Families were stratified on the presence or absence of clinical features associated with connective tissue disorders (CTDs) since CMI and CTDs frequently co-occur and it has been proposed that CMI patients with CTDs represent a distinct class of patients with a different underlying disease mechanism. Stratified linkage analyses resulted in a marked increase in evidence of linkage to multiple genomic regions consistent with reduced genetic heterogeneity. Of particular interest were two regions (Chr8, Max LOD = 3.04; Chr12, Max LOD = 2.09) identified within the subset of "CTD-negative" families, both of which harbor growth differentiation factors (GDF6, GDF3) implicated in the development of Klippel-Feil syndrome (KFS). Interestingly, roughly 3-5% of CMI patients are diagnosed with KFS. In order to investigate the possibility that CMI and KFS are allelic, GDF3 and GDF6 were sequenced leading to the identification of a previously known KFS missense mutation and potential regulatory variants in GDF6. This study has demonstrated the value of reducing genetic heterogeneity by clinical stratification implicating several convincing biological candidates and further supporting the hypothesis that multiple, distinct mechanisms are responsible for CMI.

Serum bilirubin levels have been associated with polymorphisms in the UGT1A1 promoter in normal populations and in patients with hemolytic anemias, including sickle cell anemia. When hemolysis occurs circulating heme increases, leading to elevated bilirubin levels and an increased incidence of cholelithiasis. We performed the first genome-wide association study (GWAS) of bilirubin levels and cholelithiasis risk in a discovery cohort of 1,117 sickle cell anemia patients. We found 15 single nucleotide polymorphisms (SNPs) associated with total bilirubin levels at the genome-wide significance level (p value

Introduction A specific algorithm has been proposed for classifying impingement related shoulder pain in athletes with overhead activity. Data on the inter-examiner reproducibility of the suggested clinical tests and criteria and their mutual dependencies for identifying subacromial impingement symptoms (SIS) are not available.Objective To test the inter-examiner reproducibility of selected tests and criteria suggested for classifying SIS and the mutual dependencies of each of the individual tests and SIS.Method A standardised three-phase protocol for clinical reproducibility studies was followed, consisting of a training, an overall agreement and a study phase. To proceed to the study phase, an overall agreement of 0.80 was required. In total 10, 20 and 44 subjects were included in the three phases, respectively. The case prevalence in the study phase was 50%. The inclusion criterion for cases was ≥3, and for controls ≤1 positive test out of four. Cohen's κ statistics were used for calculating agreement.Results In the overall agreement phase, an agreement of 0.90 was obtained, while in the study phase it was 0.98 with a κ of 0.95 for SIS. κ Values for the individual tests varied between 0.60 and 0.95. Mutual dependencies between each test and SIS showed Neer's test with anterior pain to be most often used to determine SIS.Conclusions Inter-examiner reproducibility was moderate to almost perfect for the selected tests and criteria for SIS. The next challenge will be to establish reproducibility in clinical practice, as well as the validity of the tests and criteria for SIS.

BACKGROUND: Although Posttraumatic Stress Disorder (PTSD) is a severe and disabling anxiety disorder, relatively few people with this condition access evidence-based care. Barriers to treatment are multiple and complex, but the emerging field of Internet therapy for PTSD may improve access to evidence-based treatment. However, little is known about the characteristics of people with PTSD who seek online treatment, or whether they perceive internet treatment as an acceptable treatment option. METHODOLOGY: An online survey was used to collect information about the demographic and symptom characteristics of individuals with elevated levels of PTSD symptoms, and this was compared to data from corresponding sample from a national survey. Previous treatment experiences, perceived barriers to treatment and treatment preferences for Internet therapy and face-to-face treatment were also compared. PRINCIPAL FINDINGS: High levels of PTSD symptoms were reported by survey respondents. Psychological distress and disability was greater than reported by individuals with PTSD from a national survey. Half of the sample reported not having received treatment for PTSD; however, 88% of those who reported receiving treatment stated they received an evidence-based treatment. Primary barriers to treatment included cost, poor awareness of service availability, lack of prior treatment response and not perceiving personal distress as severe enough to warrant treatment. Most survey respondents indicated they were willing to try Internet treatment for PTSD. CONCLUSIONS: The Internet sample was symptomatically severe and multiple barriers existed to treatment. Internet therapy is an acceptable option for the treatment of PTSD in an internet sample.