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Muscle strength in people on haemodialysis is associated with nutritional status, quality of life, functional independence and survival. Handgrip Strength (HGS) is simple to measure, but clinical interpretation is limited by the lack of reference ranges for a haemodialysis population. This study aims to define a novel parameter, HGS index, which quantifies degree of clinical weakness specific to a haemodialysis population and to test if this predicts survival.In a cross-sectional single centre study HGS was measured in stable participants on haemodialysis. HGS in the well-nourished subgroup, was used to develop a predictive equation for "expected" HGS according to demographic variables. This then was compared to observed HGS resulting in HGS index (%), an individualised parameter indicating weakness due to clinical variables whilst accounting for demographic contributors to strength. The association between HGS index and survival was explored in all participants.Amongst 427 well-nourished individuals on haemodialysis, HGS was strongly associated with demographic variables and predicted in males by the equation: HGS(kg) = 0.38*height(cm) - 0.31*age(years) - 18, and in females by the equation: HGS(kg) = 0.25*height(cm) - 0.11*age(years) - 16. Amongst 547 participants (22% with protein energy wasting), lower HGS index was associated with diabetes (p=0.004), lower body mass index (p=0.005), lower albumin (p=0.033) and longer dialysis vintage (p=0.007). Over a mean observation period of 2.8 years, quintile of HGS index was strongly associated with survival (p=0.023), and in a Cox Proportional Hazards model, the independent predictors of mortality were age, albumin, body mass index and HGS index.HGS index, defined as observed relative to expected HGS, is an individualised measure of clinical weakness. It is a novel parameter which independently predicts survival. HGS index improves the detection of clinically relevant muscle weakness in people on haemodialysis, opening up the possibility of earlier, individualised interventions and improving outcomes in this vulnerable group.

Background: Lifestyle impacts the health of kidney transplant recipients (KTRs) who are at risk of weight gain, post-transplantation diabetes mellitus and dyslipidaemia. Their capacity to self-care is key to adapting the lifestyle choices that impact their health. Aims: This qualitative study aimed to understand KTRs’ lifestyle choices in relation to their post-transplant life and explore the impact of support provided by healthcare professionals (HCPs) and significant others on KTR's self-care. Methods: The project involved 33 participants who were involved in one of five focus groups, or 15 one-to-one semi-structured interviews. The participants were KTRs who had received a transplant over 6 months or more ago, their significant others and healthcare professionals. Participants were all selected from one UK transplant centre. Purposive sampling ensured both a diversity of KTRs and a range of professionals participating, with data analysed using thematic framework analysis. Findings: The authors report on a number of selected themes. These themes draw from a larger, more extensive analysis and conceptual framework concerning health, wellbeing and lifestyle, and they identify how effective health communicative interactions and health literacy plays an integral role in developing KTRs’ self-care. Conclusion: Supporting KTR's lifestyle choices post-transplant involves building self-care capacity through effective health communication and health literacy.

This conceptual design report provides a detailed account of the European Spallation Source neutrino Super Beam (ESS$\nu$SB) feasibility study. This facility has been proposed after the measurements reported in 2012 of a relatively large value of the neutrino mixing angle $\theta_{13}$, which raised the possibility of observing potential CP violation in the leptonic sector with conventional neutrino beams. The measured value of $\theta_{13}$ also privileges the $2^{nd}$ oscillation maximum for the discovery of CP violation instead of the more typically studied $1^{st}$ maximum. The sensitivity at this $2^{nd}$ oscillation maximum is about three times higher than at the $1^{st}$ one, which implies a reduced influence of systematic errors. Working at the $2^{nd}$ oscillation maximum requires a very intense neutrino beam with an appropriate energy. The world's most intense pulsed spallation neutron source, the European Spallation Source (ESS), will have a proton linac operating at 5\,MW power, 2\,GeV kinetic energy and 14~Hz repetition rate (3~ms pulse duration, 4\% duty cycle) for neutron production. In this design study it is proposed to double the repetition rate and compress the beam pulses to the level of microseconds in order to provide an additional 5~MW proton beam for neutrino production. The physics performance has been evaluated for such a neutrino super beam, in conjunction with a megaton-scale underground water Cherenkov neutrino detector installed at a distance of 360--550\,km from ESS. The ESS proton linac upgrades, the accumulator ring required for proton-pulse compression, the target station design and optimisation, the near and far detector complexes, and the physics potential of the facility are all described in this report. The ESS linac will be operational by 2025, at which point the implementation of upgrades for the neutrino facility could begin., Comment: 216 pages

PROteolysis TArgeting Chimeras (PROTACs) are a powerful modality in drug discovery, offering the potential to address outstanding medical challenges. However, the synthetic feasibility of PROTACs, and the empiric and complex nature of their structure-activity relationships continue to present formidable limitations. As such, modular and reliable approaches to streamline the synthesis of these compounds are highly desirable. Here, we describe a robust ruthenium-catalysed late-stage C‒H amidation strategy, to provide modular access to both fully elaborated PROTACs and drug conjugates. Using readily available dioxazolone reagents, a broad range of inherently present functional groups can guide the C–H amidation on complex bioactive molecules. High selectivity and functional group tolerance enable the late-stage installation of linkers bearing orthogonal functional handles for downstream elaboration. Finally, the single-step synthesis of PROTAC and biotin conjugates is demonstrated, showcasing the potential of this methodology to provide efficient and sustainable access to advanced therapeutics and chemical biology tools.

As part of the development of the beam imaging system at the European Spallation Source, luminescent screens have been fabricated by the flame spraying of scintillating materials onto stainless steel backings. A total of seven screens were produced, three of chromia alumina (Al2O3:Cr), two of YAG (Y3Al5O12:Ce) and two of a 50/50 mix of these. The properties of these screens under proton irradiation were evaluated using a 2.55 MeV proton beam at currents of up to 10 A. Irradiation times were up to 25 h per sample, during which luminescence-, spectrographic-, thermal- and current-data was sampled at a rate of 1 Hz. Preliminary results of these measurements are reported here; with a quantitative analysis presented for one of the chromia alumina screens and a qualitative comparison of all three material types. The luminescent yield for chromia alumina was determined to be around 2000 photons/MeV for a virgin screen, and was found to drop to 1.5% after 167 mC of proton irradiation. A recovery of the luminescence of chromia alumina to >60% was observed after beam current was reduced for an 8 h period. Observations indicate that the YAG and mixed composition screens retain higher luminescence than the chromia alumina even at temperatures of over 200 °C. It is indicated that the luminescence from YAG feeds the R-lines of chromia alumina in the mixed composition screens.

Background: Few studies have examined the association between the acute:chronic workload ratio (ACWR) and complaints/injuries in young tennis players. Primary aims of this study were to investigate if accumulated external workload “spikes” in ACWR of tennis training, match play, and fitness training, and to see if high or low workload/age ratio were associated with the rate of shoulder complaints/injuries in competitive adolescent tennis players. Additional aims were to report the incidence of complaints/injuries stratified by sex and level of play and to describe shoulder injury characteristics. Hypothesis: Rapid increases in external workload are associated with the incidence of shoulder complaints and injuries. Study Design: A cohort study. Level of Evidence: Level 3. Methods: At baseline, 301 adolescent competitive tennis players, 13 to 19 years, were screened and followed weekly for 52 weeks with questionnaires, in the years 2018 to 2019. Information about time-varying accumulated external workload spikes (uncoupled ACWR >1.3), and workload/age ratio, in 252 uninjured players were used in Cox regression analyses with the outcomes shoulder complaints (≥20) and injuries (≥40) (Oslo Sports Trauma Research Center Overuse Injury Questionnaire). Results: For each additional workload spike in tennis training/match play, the hazard rate ratio (HRR) was 1.26 (95% CI, 1.13-1.40) for a shoulder complaint and 1.26 (95% CI, 1.15-1.39) for a shoulder injury. The HRR for fitness training was 1.11 (95% CI, 1.02-1.20) for a shoulder complaint and 1.18 (95% CI, 1.09-1.27) for a shoulder injury. Workload/age ratio was not associated with the rate of shoulder complaints or injuries. Conclusion: Accumulated external workload spikes of tennis training, match play, and/or fitness training are associated with a higher rate of shoulder complaints and shoulder injuries in competitive adolescent tennis players. Clinical Relevance: Consistency in training load on a weekly basis is most likely more beneficial for adolescent tennis players regarding shoulder complaints/injuries than a training schedule comprising rapid increases (ie, spikes) in workload.

Background and aims: The conditions for jejunal glucose absorption in healthy subjects have not been thoroughly studied. In this study we investigated differences in the jejunal villi enlargement factor, as well as ultrastructural aspects of the surface enterocytes and mitochondria, comparing 2 weeks of high-carbohydrate (HCD) versus high-fat diets (HFD). We also measured the ketogenesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) in relation to jejunal mitochondria. Methods: A single-centre, randomized, unblinded crossover study in 15 healthy volunteers ingesting strictly controlled equicaloric diets (either HCD or HFD), with 60% energy from the respective source. An enteroscopy was carried out after 2 weeks of each diet and jejunal mucosal biopsies were acquired. Conventional histology, immunofluorescent staining, transmission electron microscopy and confocal microscopy were used. Results: The villi did not demonstrate any change in the epithelial enlargement factor. Despite an increased mitosis, there were no changes in apoptotic indices. However, the ultrastructural analysis demonstrated a significant increase in the enlargement factor at the bases of the villi. The mitochondria demonstrated increased amounts of cristae after the HFD. The confocal microscopy revealed increased HMGCS2 per mitochondrial marker at the top of the villi after the HFD compared to the HCD. Conclusion: There is a morphometric adaption in the jejunal mucosa following the 2-week diets, not only on a histological level, but rather on the ultrastructural level. This study supports the notion that mitochondrial HMGCS2 is regulated by the fat content of the diet and is involved in the expression of monosaccharide transporters.

Bird‐mediated dispersal is presumed to be important in the dissemination of many different types of organisms, but concrete evidence remains scarce. This is especially true for biota producing microscopic propagules. Tree‐dwelling birds, such as woodpeckers, would seem to represent ideal dispersal vectors for organisms growing on standing tree trunks such as epiphytic lichens and fungi. Here, we utilize bird natural history collections as a novel source of data for studying dispersal ecology of plants, fungi, and microorganisms. We screened freshly preserved specimens of three Finnish woodpecker species for microscopic propagules. Samples were taken from bird feet, and chest and tail feathers. Propagules were extracted using a sonication–centrifugation protocol, and the material obtained was studied using light microscopy. Diverse biological material was recovered from all specimens of all bird species, from all positions sampled. Most abundant categories of discovered biological material included bryophyte fragments, fungal spores, and vegetative propagules of lichens. Also, freshwater diatoms, bryophyte spores, algal cells, testate amebae, rotifers, nematodes, pollen, and insect scales were identified. The method developed here is applicable to living specimens as well, making it a versatile tool for further research. Our findings highlight the potential of bird‐mediated dispersal for diverse organisms and showcase the use of natural history collections in ecological research., Woodpeckers are ideal candidates for bird‐mediated dispersal for a diverse set of organisms, especially epiphytes. We report high loads of diverse biological propagules extracted from feathers and feet of woodpecker specimens from natural history collections. The study highlights the potential of birds as dispersal vectors of lichens, fungi, bryophytes, and more.

There is a need to assess whether the resources invested in building trauma competence in services actually lead to higher levels of competence. For this purpose, we have developed an instrument called the Trauma and Development Education Monitor (TANDEM). The present article presents the process behind developing the instrument and an initial study of its psychometric properties. The tested version consisted of 59 items distributed across the domains of readiness, agency, reflexivity, knowledge, practice and culture at work. Based on responses from 415 professionals in relevant services, concept and criterion validity was examined through reliability analyses, factor analyses and regression analyses. Based on the analyses, the tested version was reduced to 54 items in the final version, distributed across the same six domains. As dimensions, the domains generally showed good scale reliability, and for the final version factor analyses confirmed a one-dimensional model for all domains. The instrument discriminated between respondents who reported more versus less previously received trauma competence building and showed specificity as a measure of trauma versus more general competence. The results indicate that TANDEM has the potential to become a useful tool in endeavours to implement trauma competence in services, as well as in research activities in this field.

Background: In young tennis players, high loads on the spine and high training volumes in relation to age are associated with a high lifetime prevalence of back pain. The primary aim of this study was to investigate if accumulated external workload “spikes” in the acute:chronic workload ratio (ACWR) of tennis training, match play, and fitness training, and if high or low workload/age ratio were associated with back pain events in competitive adolescent tennis players. Additional aims were to report the incidence of back pain stratified by sex and level of play and to describe the characteristics of players with back pain. Hypothesis: Rapid increases in external workload are associated with the incidence of back pain. Study Design: Cohort study of 198 competitive tennis players, 13 to 19 years, with a weekly follow-up for 52 consecutive weeks. Level of Evidence: Level 3. Methods: Accumulated external workload spikes (uncoupled ACWR >1.3), and the workload/age ratio, were time-varying exposures in Cox regression analyses with the outcome back pain (pain intensity ≥2/10 in the lower back and/or in the upper back/neck with a pain-related disability). Results: For each additional workload spike in tennis training/match play, the hazard rate ratio (HRR) was 1.17 (95% CI, 1.06-1.28) for back pain. The corresponding HRR for fitness training was 1.13 (95% CI, 1.05-1.22). Training workload/age ratio was not related to back pain. Conclusion: Accumulated external workload spikes of tennis training, match play, and/or fitness training are associated with a higher rate of back pain events in competitive adolescent tennis players. Clinical Relevance: Back pain is a troublesome clinical problem that may affect the performance of talented young tennis players. Structuring the training schedule to minimize rapid increases (ie, spikes) of training load on a weekly basis may enhance performance and reduce back pain in adolescent tennis players.

Developmental alcohol exposure results in altered neuroimmune function in both humans and rodents. Given the critical role for the principle neuroimmune cell, microglia, in maintaining synaptic form and function, microglial dysfunction in the cerebellum may be an important mechanism underlying the aberrant cerebellar connectivity observed in rodent models of fetal alcohol spectrum disorders. Using an established rodent model of alcohol exposure during human third-trimester fetal development, we examine the cerebellum of male and female Long Evans rats to determine the impact of early postnatal alcohol exposure on cerebellar microglia, and the potential therapeutic effects of an adolescent intervention consisting of voluntary exercise (running). All cerebelli were examined at postnatal day 42 (i.e., late adolescence), and microglia were labeled with Iba1, a microglia-specific protein. Early postnatal alcohol exposure caused an increase in microglial density throughout cerebellum and a reduction in cerebellar volume, and a reduction in the proportion of fully ramified (often called "resting state") microglia selective to lobules 1-4. In contrast, adolescent exercise decreased microglial density throughout cerebellum and increased cerebellar volume, while activating microglia (as indicated by increases in amoeboid microglia, and reductions in fully and partially ramified microglia) selectively in lobules 1-4. These results suggest that adolescent exercise may be a suitable intervention to ameliorate alcohol-induced neuroimmune dysfunction as it alters microglia density and cerebellar volume in opposite to the effects of developmental alcohol exposure. Importantly, exercise intervention can be flexibly implemented well after the time window of vulnerability to alcohol.

Research on evolutionary forces determining optimal body sizes has primarily relied on experimental evaluation of respective selective pressures. Accounting for among-species variation through application of phylogenetic comparative methods is a complementary although little used approach. It enables the direct association of body size values with particular environments. Using phylogenetically explicit comparative analyses, we show that small body size is associated with diurnal (rather than nocturnal) activity of adults among temperate species of the moth family Geometridae. The association of an exclusively adult trait with species-specific body size suggests that optimal body sizes are at least partly determined by the costs being a large adult, as opposed to the more frequently considered costs of attaining large size. It appears likely that size-selective predation by insectivorous birds is the primary factor responsible for selection against large body size in day-flying moths.

Peer-assisted learning has gained momentum in a variety of disciplines, including medical education. In Gothenburg, Sweden, medical students who have finished their compulsory anatomy courses have the option of working as teaching assistants (TAs). Teaching assistants provide small group teaching sessions as a complement to lectures given by faculty. Previously, TAs were left to handle the role as junior teachers by themselves, but since 2011, a continuation course in anatomy has been developed with the aim of providing the TAs better anatomy knowledge and guidance for teaching. The course was designed to comprise 7.5 ECTS credits (equivalent to 5 weeks of full-time studies), and today all TAs are required to take this course before undertaking their own teaching responsibilities. This study aims to compare course evaluations of TA teaching before and after the introduction of the anatomy continuation course, in order to understand how students perceived teaching performed by self-learned versus trained TAs. The results of this study demonstrate that there was a trend towards better teaching performed by trained TAs. The variability in rankings decreased significantly after the introduction of the continuation course. This was mainly due to an improvement among the TAs with the lowest levels of performance. In addition to comparing student rankings, TAs were interviewed regarding their experiences and perceptions within the continuation course. The course was generally positively regarded. The TAs described a sense of cohesion and appreciation since the institute invested in a course dedicated specifically for them. Anat Sci Educ 11: 403-409. © 2018 American Association of Anatomists.

Shoulder injuries and sports-related shoulder pain are substantial burdens for athletes performing a shoulder loading sport. The burden of shoulder problems in the athletic population highlights the need for prevention strategies, effective rehabilitation programs, and a individually based return-to-play (RTP) decision. The purpose of this clinical commentary is to discuss each of these 3 challenges in the sporting shoulder, to assist the professional in: (1) preventing injury; (2) providing evidence-based practice rehabilitation and; (3) to guide the athlete toward RTP. The challenges for injury prevention may be found in the search for (the interaction between) relevant risk factors, develop valid screening tests, and implement feasible injury prevention programmes with maximal adherence from the athletes. Combined analytical and functional testing seems mandatory screening an athlete's performance. Many questions arise when rehabilitating the overhead athlete, from exercise selection, over the value of stretching, toward kinetic chain implementation and progression to high performance training. Evidence-based practice should be driven by the available research, clinical expertise and the patient's expectations. Deciding when to return to sport after a shoulder injury is complex and multifactorial. The main concern in the RTP decision is to minimize the risk of re-injury. In the absence of a "gold standard", clinicians may rely on general guidelines, based on expert opinion, regarding cutoff values for normal range of motion, strength and function, with attention to risk tolerance and load management.

There is increasing evidence that titanium dioxide (TiO2) nanoparticles (NPs) present in water or diet can be taken up by fish and accumulate in internal organs including the liver. However, their further fate in the organ is unknown. This study provides new insights into the interaction, uptake mechanism, intracellular trafficking, and fate of TiO2 NPs (Aeroxide® P25) in fish liver parenchymal cells (RTL-W1) in vitro using high-resolution transmission electron microscopy (TEM) and single particle inductively coupled plasma mass spectrometry (spICP-MS) as complementary analytical techniques. The results demonstrate that following their uptake via caveolae-mediated endocytosis, TiO2 NPs were trafficked through different intracellular compartments including early endosomes, multivesicular bodies, and late endosomes/endo-lysosomes, and eventually concentrated inside multilamellar vesicles. TEM and spICP-MS results provide evidence that uptake was nano-specific. Only NPs/NP agglomerates of a specific size range (~ 30–100 nm) were endocytosed; larger agglomerates were excluded from uptake and remained located in the extracellular space/exposure medium. NP number and mass inside cells increased linearly with time and was associated with an increase in particle diameter suggesting intracellular agglomeration/aggregation. No alterations in the expression of genes regulated by the redox balance-sensitive transcription factor Nrf-2 including superoxide dismutase, glutamyl cysteine ligase, glutathione synthetase, glutathione peroxidase, and glutathione S-transferase were observed. This shows that, despite the high intracellular NP burden (~ 3.9 × 102 ng Ti/mg protein after 24 h) and NP-interaction with mitochondria, cellular redox homeostasis was not significantly affected. This study contributes to a better mechanistic understanding of in vitro particokinetics as well as the potential fate and effects of TiO2 NPs in fish liver cells. Electronic supplementary material The online version of this article (10.1007/s11356-019-04856-1) contains supplementary material, which is available to authorized users.

BackgroundMyocardial ischemia is associated with alterations in cardiac metabolism, resulting in decreased fatty acid oxidation and increased lipid accumulation. Here we investigate how myocardial lipid content and dynamics affect the function of the ischemic heart, and focus on the role of the lipid droplet protein perilipin 5 (Plin5) in the pathophysiology of myocardial ischemia.Methods and resultsWe generated Plin5−/− mice and found that Plin5 deficiency dramatically reduced the triglyceride content in the heart. Under normal conditions, Plin5−/− mice maintained a close to normal heart function by decreasing fatty acid uptake and increasing glucose uptake, thus preserving the energy balance. However, during stress or myocardial ischemia, Plin5 deficiency resulted in myocardial reduced substrate availability, severely reduced heart function and increased mortality. Importantly, analysis of a human cohort with suspected coronary artery disease showed that a common noncoding polymorphism, rs884164, decreases the cardiac expression of PLIN5 and is associated with reduced heart function following myocardial ischemia, indicating a role for Plin5 in cardiac dysfunction.ConclusionOur findings indicate that Plin5 deficiency alters cardiac lipid metabolism and associates with reduced survival following myocardial ischemia, suggesting that Plin5 plays a beneficial role in the heart following ischemia.

The specific aim of the study was to investigate and compare epiphyseal length and extension in the proximal humerus, closure in the growth plate and bone marrow signal intensity related to the proximal humeral physis in the dominant arm and the non-dominant arm of the asymptomatic adolescent elite tennis player. The study sample included 35 asymptomatic elite young tennis players (15 males and 20 females, mean age 17.4 years ± 2.7). Each player contributed with two shoulders to the MRI measurement. The non-dominant arm was used as a control. Relative reliability between the radiologists was excellent (ICC 0.78–0.96). Statistically significant differences between dominant arm and non-dominant arm in epiphyseal length (mm) laterally (DA 27.3 vs NDA 26.7) were shown. Statistically significant differences were also found in epiphyseal extension (mm) laterally (DA 36.1 vs NDA 35.1) and ventrally (DA 36.2 vs NDA 34.8). No statistically significant differences were found between dominant arm and non-dominant arm in epiphyseal extension (mm) medially (DA 31.7 vs NDA 31.7) and dorsally (DA 22.6 vs NDA 22.1). Significant findings assessing MRI measurements of the epiphyseal plate in the asymptomatic adolescent elite tennis player might reflect a development of consecutive alterations in the epiphyseal plate in the dominant arm. Diagnostic study, Level IV.

Context Tennis is an asymmetric overhead sport with specific muscle-activation patterns, especially eccentrically in the rotator cuff. Magnetic resonance imaging (MRI) findings in asymptomatic adolescent elite tennis players have not previously been reported. Objective The first aim of the study was to describe MRI findings regarding adaptations or abnormalities, as well as muscle cross-sectional area (CSA), of the rotator cuff. The second aim of the study was to investigate the rotator cuff based on the interpretation of the MRI scans as normal versus abnormal, with the subdivision based on the grade of tendinosis, and its association with eccentric rotator cuff strength in the dominant arm (DA) of the asymptomatic elite adolescent tennis player. Setting Testing environment at the radiology department of Medicinsk Röntgen AB. Patients or Other Participants Thirty-five asymptomatic elite tennis players (age = 17.4 ± 2.7 years) were selected based on ranking and exposure time. Intervention(s) We assessed MRI scans and measured the CSA of the rotator cuff muscle. The non-DA (NDA) was used as a control. In addition, eccentric testing of the external rotators of the DA was performed with a handheld dynamometer. Results The DA and NDA displayed different frequencies of infraspinatus tendinosis (grade 1 changes) (P < .05). Rotator cuff measurements revealed larger infraspinatus and teres minor CSA (P < .05) in the DA than in the NDA. Mean eccentric external-rotation strength in the DA stratified by normal tendon and tendinosis was not different between groups (P = .723). Conclusions Asymptomatic adolescent elite tennis players demonstrated infraspinatus tendinosis more frequently in the DA than in the NDA. Clinicians must recognize these tendon changes in order to modify conditioning and performance programs appropriately.

ObjectiveTo assess the evidence for risk factors and prevention measures for shoulder injuries in overhead sports.DesignSystematic review with best-evidence synthesis.Data sourcesMedline (Ovid), PubMed (complementary search), Embase (Elsevier), Cochrane (Wiley), SPORTDiscus (Ebsco) and Web of Science Core Collection (Thomson Reuters), from 1 January 1990 to 15 May 2017.Eligibility criteria for selecting studiesRandomised controlled trials, cohort studies and case-control studies on risk factors or prevention measures for shoulder injuries in overhead sports. The eligible studies were quality assessed using the Scottish Intercollegiate Guidelines Network criteria.ResultsOf 4778 studies identified, 38 were eligible for quality review and 17 met the quality criteria to be included in the evidence synthesis. One additional quality study presented a shoulder injury prevention programme. Most studies focused on baseball, lacrosse or volleyball (n=13). The risk factors examined included participation level (competition vs training) (n=10), sex (n=4), biomechanics (n=2) and external workload (n=2). The evidence for all risk factors was limited or conflicting. The effect of the prevention programme within the subgroup of uninjured players at baseline was modest and possibly lacked statistical power.ConclusionsAll investigated potential risk factors for shoulder injury in overhead sports had limited evidence, and most were non-modifiable (eg, sex). There is also limited evidence for the effect of shoulder injury prevention measures in overhead sports.PROSPERO trial registration numberCRD42015026850.

Background: Elevated plasma levels of troponin in acute stroke patients are common and have in several studies been shown to predict in-hospital and short-term mortality. Little is, however, known about the long-term prognosis of these patients. The aim of this study was to determine patient characteristics and 5-year mortality in patients with acute stroke and troponin elevation on admission. Methods: A retrospective cohort study of all consecutive patients with acute stroke and a plasma troponin I (TnI) analyzed on admission to Danderyd Hospital between January 1, 2005, and January 1, 2006 (n = 247). Patient characteristics were obtained from the Swedish National Stroke Register, Riksstroke, as well as hospital records. Mortality data were obtained from the Swedish Cause of Death Register. Results: There were 133 patients (54%) with TnI less than .03 mu g/L (normal), 74 patients (30%) with TnI .03-.11 mu g/L (low elevation), and 40 patients (16%) with TnI greater than .11 mu g/L (high elevation). TnI elevations were associated with a higher age, prior ischemic stroke, chronic heart failure, renal insufficiency, stroke severity, and ST segment elevation or depression on admission. The rate of hyperlipidemia decreased with increasing TnI. Adjusted for age and comorbidity, elevated TnI values on admission had a significantly and sustained increased mortality over the 5-year follow-up, with a hazard ratio of 1.90 (95% confidence interval, 1.33-2.70). Conclusions: Troponin elevation in patients with acute stroke, even when adjusted for several possible confounders, is associated with an almost 2-fold increased risk of 5-year mortality.

The frequently used concept of “global reaction” is discussed and the reason for the confusion behind explained. The misconception is cleared by formula writing based on the donor–acceptor (donac) reaction concept and by applying the Grand Rule of Formula Writing that is based on it.

Peer-assisted learning has gained momentum in a variety of disciplines, including medical education. In Gothenburg, Sweden, medical students who have finished their compulsory anatomy courses have the option of working as teaching assistants (TAs). Teaching assistants provide small group teaching sessions as a complement to lectures given by faculty. Previously, TAs were left to handle the role as junior teachers by themselves, but since 2011, a continuation course in anatomy has been developed with the aim of providing the TAs better anatomy knowledge and guidance for teaching. The course was designed to comprise 7.5 ECTS credits (equivalent to 5 weeks of full-time studies), and today all TAs are required to take this course before undertaking their own teaching responsibilities. This study aims to compare course evaluations of TA teaching before and after the introduction of the anatomy continuation course, in order to understand how students perceived teaching performed by self-learned versus trained TAs. The results of this study demonstrate that there was a trend towards better teaching performed by trained TAs. The variability in rankings decreased significantly after the introduction of the continuation course. This was mainly due to an improvement among the TAs with the lowest levels of performance. In addition to comparing student rankings, TAs were interviewed regarding their experiences and perceptions within the continuation course. The course was generally positively regarded. The TAs described a sense of cohesion and appreciation since the institute invested in a course dedicated specifically for them. Anat Sci Educ 11: 403-409. © 2018 American Association of Anatomists.

Objectives To present and compare antibiotic prescribing for inpatients among the most common non-bacterial diagnoses groups at medicine departments of a teaching (TH) and a non-teaching hospital (NTH) in central India. Setting An observational cross-sectional study was conducted at two tertiary care settings in Ujjain district, Madhya Pradesh, India. Data and participants The data were collected manually, using a customised form. Complete records of all inpatients, who were >15 years of age and had stayed for at least one night in either of the hospitals during 2008–2011, were analysed. Outcome measures Inpatients were grouped according to the presence or absence of a bacterial infectious diagnosis, viral/malaria fever or cardiovascular disease. Classes of antibiotics prescribed to these groups and adherence to the available prescribing guidelines were compared between the hospitals using the notes from the patient files and the diagnoses. Results Of 20 303 inpatients included in the study, 66% were prescribed antibiotics. Trade name prescribing and use of broad-spectrum antibiotics were more frequent at the NTH than at the TH (p

IMPORTANCE The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.

Context Tennis requires repetitive overhead movements that can lead to upper extremity injury. The scapula and the shoulder play a vital role in injury-free playing. Scapular dysfunction and glenohumeral changes in strength and range of motion (ROM) have been associated with shoulder injury in the overhead athlete. Objective To compare scapular position and strength and shoulder ROM and strength between Swedish elite tennis players of 3 age categories (16 years). Design Cross-sectional study. Setting Tennis training sports facilities. Patients or Other Participants Fifty-nine adolescent Swedish elite tennis players (ages 10–20 years) selected based on their national ranking. Main Outcome Measure(s) We used a clinical screening protocol with a digital inclinometer and a handheld dynamometer to measure scapular upward rotation at several angles of arm elevation, isometric scapular muscle strength, glenohumeral ROM, and isometric rotator cuff strength. Results Players older than 16 years showed less scapular upward rotation on the dominant side at 90° and 180° (P < .05). Although all absolute scapular muscle strength values increased with age, there was no change in the body-weight–normalized strength of the middle (P = .9) and lower (P = .81) trapezius or serratus anterior (P = .17). Glenohumeral internal-rotation ROM and total ROM tended to decrease, but this finding was not statistically significant (P = .052 and P = .06, respectively). Whereas normalized internal-rotator strength increased from 14 to 16 years to older than 16 years (P = .009), normalized external-rotator and supraspinatus strength remained unchanged. Conclusions Age-related changes in shoulder and scapular strength and ROM were apparent in elite adolescent tennis players. Future authors should examine the association of these adaptations with performance data and injury incidence.

The bacterium Staphylococcus aureus utilizes a variety of different mechanisms to survive unfavorable stress conditions that are critical for its persistence in the environment and for pathogenicity. The staphylococcal DnaK heat shock system functions as a major protein folding machine under stress conditions that cause aggregation and un-folding of proteins. In prior studies, S. aureus cells with a non-functional DnaK system showed reduced tolerance to heat, oxidative and antibiotic stresses, a lowered carotenoid production, and decreased survival in a murine host. This study provides insights that the altered phenotypes of the dnaK mutant cells are not due to decreased SigB activity in the mutant cell. Transcriptomic profiling studies provide evidence that a large number of genes encoding proteins involved in cell wall biogenesis, virulence and general stress tolerance, and genes encoding proteins involved in metabolic processes are differentially regulated in dnaK mutant cells relative to wild-type S. aureus. It was also determined that loss of functional DnaK caused a reduction in the ability of S. aureus to make biofilms and its adherence to eukaryotic cells. This study provides evidence of a global significance of DnaK heat shock system in S. aureus.

Background: Although smoking and HPV infection are recognized as important risk factors for oropharyngeal cancer, how their joint exposure impacts on oropharyngeal cancer risk is unclear. Specifically, whether smoking confers any additional risk to HPV-positive oropharyngeal cancer is not understood. Methods: Using HPV serology as a marker of HPV-related cancer, we examined the interaction between smoking and HPV16 in 459 oropharyngeal (and 1445 oral cavity and laryngeal) cancer patients and 3024 control participants from two large European multicentre studies. Odds ratios and credible intervals [CrI], adjusted for potential confounders, were estimated using Bayesian logistic regression. Results: Both smoking [odds ratio (OR [CrI]: 6.82 [4.52, 10.29]) and HPV seropositivity (OR [CrI]: 235.69 [99.95, 555.74]) were independently associated with oropharyngeal cancer. The joint association of smoking and HPV seropositivity was consistent with that expected on the additive scale (synergy index [CrI]: 1.32 [0.51, 3.45]), suggesting they act as independent risk factors for oropharyngeal cancer. Conclusions: Smoking was consistently associated with increase in oropharyngeal cancer risk in models stratified by HPV16 seropositivity. In addition, we report that the prevalence of oropharyngeal cancer increases with smoking for both HPV16-positive and HPV16-negative persons. The impact of smoking on HPV16-positive oropharyngeal cancer highlights the continued need for smoking cessation programmes for primary prevention of head and neck cancer.

PurposeThe authors have developed the Leadership‐Employeeship‐Relationship Model and a questionnaire following their conceptualization of the employeeship concept. It is possible to separately study leadership, peer employee, and interactive leader‐follower behaviors. The purpose of this paper is to examine the relationship between the conceptualization and operationalization, as well as between the model and psychological climate.Design/methodology/approachIn total, four organizations operating at an airport participated. The quantitative approach involved data gathered from expected leadership and employee behaviors and psychological climate attitude questionnaires. The leadership and peer employee variables are separately based on the leadership and employeeship questionnaires, whereas the leader‐follower variable is based on the results of both questionnaires. All analyses were made on the variable level.FindingsThe results show that expected leadership, peer employee, and congruent leader‐follower behaviors all have a positive correlation with psychological climate. Hierarchical regression analyses indicated that congruent leader‐follower behavior had augmented value to leadership behavior and its relationship to psychological climate.Practical implicationsCongruent leader‐follower behavior plays an important role in the overall improvement of psychological climate. Steps toward congruent behavior are to allow followers to participate in leadership development and that the issue of shared responsibilities and authority is best managed in collaboration between management and staff.Originality/valueThe paper is the first to demonstrate empirically the relation between the interactive leader‐follower employeeship perspective based on the expected behaviors of both leaders and followers and psychological climate.

MUC2, the major colonic mucin, forms large polymers by N-terminal trimerization and C-terminal dimerization. Although the assembly process for MUC2 is established, it is not known how MUC2 is packed in the regulated secretory granulae of the goblet cell. When the N-terminal VWD1-D2-D′D3 domains (MUC2-N) were expressed in a goblet-like cell line, the protein was stored together with full-length MUC2. By mimicking the pH and calcium conditions of the secretory pathway we analyzed purified MUC2-N by gel filtration, density gradient centrifugation, and transmission electron microscopy. At pH 7.4 the MUC2-N trimer eluted as a single peak by gel filtration. At pH 6.2 with Ca 2+ it formed large aggregates that did not enter the gel filtration column but were made visible after density gradient centrifugation. Electron microscopy studies revealed that the aggregates were composed of rings also observed in secretory granulae of colon tissue sections. The MUC2-N aggregates were dissolved by removing Ca 2+ and raising pH. After release from goblet cells, the unfolded full-length MUC2 formed stratified layers. These findings suggest a model for mucin packing in the granulae and the mechanism for mucin release, unfolding, and expansion.

The ability to generate particles from the quantum vacuum is one of the most profound consequences of Heisenberg's uncertainty principle. Although the significance of vacuum fluctuations can be seen throughout physics, the experimental realization of vacuum amplification effects has until now been limited to a few cases. Superconducting circuit devices, driven by the goal to achieve a viable quantum computer, have been used in the experimental demonstration of the dynamical Casimir effect, and may soon be able to realize the elusive verification of analog Hawking radiation. This Colloquium article describes several mechanisms for generating photons from the quantum vacuum and emphasizes their connection to the well-known parametric amplifier from quantum optics. Discussed in detail is the possible realization of each mechanism, or its analog, in superconducting circuit systems. The ability to selectively engineer these circuit devices highlights the relationship between the various amplification mechanisms.

Background Glenohumeral internal rotation deficit (GIRD) and posterior shoulder stiffness have been associated with impingement symptoms in the overhead athlete. Stretching of the posterior shoulder is advised in injury prevention as well as rehabilitation programs. The purpose of the present study was to determine if stretching of the posterior shoulder improves ROM and reduces symptoms, and to compare angular with non-angular stretching techniques. Methods 60 overhead athletes with GIRD (age 25 ± 7.2 years, height 176 ± 8 cm, weight 69.8 ± 10.2 kg) participated to the study. Thirty athletes had no shoulder pain, 30 had impingement symptoms on the dominant shoulder. The subjects were randomly assigned into an “angular” or a “non-angular” treatment group. They were treated for 3 weeks (9 sessions) and followed for another period of 3 weeks after completion of the treatment. Treatment outcome variables were glenohumeral internal rotation range of motion, and, in the patient group, pain (VAS) scores and functional performance (ROWE-score). Results Statistical analysis showed a significant increase in ROM ( p < .05) in both treatment groups, in the patient as well as in the healthy control group. In addition, patients showed a significant improvement in pain assessment scores, and a significant increase in the Modified Rowe Score. There were no significant differences between both treatment techniques. Discussion Stretching, angular as well as non-angular techniques, increases internal rotation ROM in overhead athletes, and may decrease sport specific shoulder pain in overhead athletes with impingement symptoms.

One of the most surprising predictions of modern quantum theory is that the vacuum of space is not empty. In fact, quantum theory predicts that it teems with virtual particles flitting in and out of existence. While initially a curiosity, it was quickly realized that these vacuum fluctuations had measurable consequences, for instance producing the Lamb shift of atomic spectra and modifying the magnetic moment for the electron. This type of renormalization due to vacuum fluctuations is now central to our understanding of nature. However, these effects provide indirect evidence for the existence of vacuum fluctuations. From early on, it was discussed if it might instead be possible to more directly observe the virtual particles that compose the quantum vacuum. 40 years ago, Moore suggested that a mirror undergoing relativistic motion could convert virtual photons into directly observable real photons. This effect was later named the dynamical Casimir effect (DCE). Using a superconducting circuit, we have observed the DCE for the first time. The circuit consists of a coplanar transmission line with an electrical length that can be changed at a few percent of the speed of light. The length is changed by modulating the inductance of a superconducting quantum interference device (SQUID) at high frequencies (~11 GHz). In addition to observing the creation of real photons, we observe two-mode squeezing of the emitted radiation, which is a signature of the quantum character of the generation process., Comment: 12 pages, 3 figures

Study design Descriptive study, cross-sectional design. Background Tennis requires repetitive overhead movement patterns that can lead to upper extremity injury. The scapula plays a vital role in injury-free playing. Scapular dysfunction has been associated with shoulder injury in the overhead athlete. Objectives The purpose of this study was to describe variables regarding scapular position, muscle strength and flexibility in young elite tennis players. Methods Thirty-five adolescent Swedish elite tennis players (19 boys, aged 13.6 (+/-1.4) years, 16 girls, aged 12.6 (+/-1.3) years), selected on the basis of their national ranking, underwent a clinical screening protocol consisting of: scapular upward rotation at several angles of arm elevation; isometric scapular muscle strength; and anthropometric measurement of pectoralis minor (PM) length. Results The players showed significantly more scapular upward rotation on their dominant side (p