An investigation of motor learning during side-step cutting, design of a randomised controlled trial

BACKGROUND: Of all athletic knee injuries an anterior cruciate ligament (ACL) rupture results in the longest time loss from sport. Regardless of the therapy chosen, conservative or reconstructive, athletes are often forced to reduce their level of physical activity and their involvement in sport. Moreover, a recent review reported prevalences of osteoarthritis ranging from 0% to 13% for patients with isolated ACL-deficient (ACL-D) knees and respectively 21% to 48% in patients with combined injuries. The need for ACL injury prevention is clear. The identification of risk factors and the development of prevention strategies may therefore have widespread health and economic implications. The focus of this investigation is to assess the role of implicit and explicit motor learning in optimising the performance of a side-step-cutting task. METHODS/DESIGN: A randomized controlled laboratory study will be conducted. Healthy basketball players, females and males, 18 years and older, with no previous lower extremity injuries, playing at the highest recreational level will be included. Subjects will receive a dynamic feedback intervention. Kinematic and kinetic data of the hip, knee and ankle and EMG activity of the quadriceps, hamstrings and gastrocnemius will be recorded. DISCUSSION: Female athletes have a significantly higher risk of sustaining an ACL injury than male athletes. Poor biomechanical and neuromuscular control of the lower limb is suggested to be a primary risk factor of an ACL injury mechanism in females. This randomized controlled trial has been designed to investigate whether individual feedback on task performance appears to be an effective intervention method. Results and principles found in this study will be applied to future ACL injury prevention programs, which should maybe more focus on individual injury predisposition. TRIAL REGISTRATION: Trial registration number NTR2250

T Cell Chemo-Vaccination Effects after Repeated Mucosal SHIV Exposures and Oral Pre-Exposure Prophylaxis

Pre-exposure prophylaxis (PrEP) with anti-viral drugs is currently in clinical trials for the prevention of HIV infection. Induction of adaptive immune responses to virus exposures during anti-viral drug administration, i.e., a “chemo-vaccination” effect, could contribute to PrEP efficacy. To study possible chemo-vaccination, we monitored humoral and cellular immune responses in nine rhesus macaques undergoing up to 14 weekly, low-dose SHIVSF162P3 rectal exposures. Six macaques concurrently received PrEP with intermittent, oral Truvada; three were no-PrEP controls. PrEP protected 4 macaques from infection. Two of the four showed evidence of chemo-vaccination, because they developed anti-SHIV CD4+ and CD8+ T cells; SHIV-specific antibodies were not detected. Control macaques showed no anti-SHIV immune responses before infection. Chemo-vaccination-induced T cell responses were robust (up to 3,940 SFU/106 PBMCs), predominantly central memory cells, short-lived (≤22 weeks), and appeared intermittently and with changing specificities. The two chemo-vaccinated macaques were virus-challenged again after 28 weeks of rest, after T cell responses had waned. One macaque was not protected from infection. The other macaque concurrently received additional PrEP. It remained uninfected and T cell responses were boosted during the additional virus exposures. In summary, we document and characterize PrEP-induced T cell chemo-vaccination. Although not protective after subsiding in one macaque, chemo-vaccination-induced T cells warrant more comprehensive analysis during peak responses for their ability to prevent or to control infections after additional exposures. Our findings highlight the importance of monitoring these responses in clinical PrEP trials and suggest that a combination of vaccines and PrEP potentially might enhance efficacy

Deep-Learning based segmentation and quantification in experimental kidney histopathology

BACKGROUND: Nephropathologic analyses provide important outcomes-related data in experiments with the animal models that are essential for understanding kidney disease pathophysiology. Precision medicine increases the demand for quantitative, unbiased, reproducible, and efficient histopathologic analyses, which will require novel high-throughput tools. A deep learning technique, the convolutional neural network, is increasingly applied in pathology because of its high performance in tasks like histology segmentation. METHODS: We investigated use of a convolutional neural network architecture for accurate segmentation of periodic acid-Schiff-stained kidney tissue from healthy mice and five murine disease models and from other species used in preclinical research. We trained the convolutional neural network to segment six major renal structures: glomerular tuft, glomerulus including Bowman\u27s capsule, tubules, arteries, arterial lumina, and veins. To achieve high accuracy, we performed a large number of expert-based annotations, 72,722 in total. RESULTS: Multiclass segmentation performance was very high in all disease models. The convolutional neural network allowed high-throughput and large-scale, quantitative and comparative analyses of various models. In disease models, computational feature extraction revealed interstitial expansion, tubular dilation and atrophy, and glomerular size variability. Validation showed a high correlation of findings with current standard morphometric analysis. The convolutional neural network also showed high performance in other species used in research-including rats, pigs, bears, and marmosets-as well as in humans, providing a translational bridge between preclinical and clinical studies. CONCLUSIONS: We developed a deep learning algorithm for accurate multiclass segmentation of digital whole-slide images of periodic acid-Schiff-stained kidneys from various species and renal disease models. This enables reproducible quantitative histopathologic analyses in preclinical models that also might be applicable to clinical studies

Prevention of Rectal SHIV Transmission in Macaques by Daily or Intermittent Prophylaxis with Emtricitabine and Tenofovir

Using a repeat-exposure macaque model, Walid Heneine and colleagues find that pre-exposure prophylaxis with combination antiretroviral drugs provides protection against rectal challenge with a SHIV virus

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

The effectiveness of game-based meditation therapy for traumatized adolescents in residential care: a randomized controlled trial (PREPRINT)

Aim: Many adolescents in residential care have experienced traumatic events and suffer from posttraumatic stress. This study examined the effectiveness of Muse, a game-based meditation intervention, as an addition to treatment as usual (TAU) for traumatized adolescents in residential care. Methods: Seventy-seven traumatized adolescents (10 – 18 years old) received either Muse and TAU (n = 37) or treatment as usual alone (n = 40). TAU consisted of evidence-based treatments that did not specifically target posttraumatic symptoms. Outcomes were measured at T1, T2, and two-months follow-up (FU). Primary outcomes were posttraumatic symptoms (self-report and mentor-report) and stress (self-report) at T2. Secondary outcomes included anxiety, depression, and aggression at T2, and all outcomes at follow-up. Results: The Muse group showed significantly greater improvements than the control group at T2 regarding self-reported posttraumatic symptoms, stress, anxiety, depression, and aggression. Mentor reports showed marginally significant decreases in posttraumatic stress at T2. There were no differences between the groups at FU, except for a marginally significant difference in self-reported posttraumatic symptoms, where the Muse participants showed larger decreases. Conclusions: Game-based meditation therapy is a promising intervention that is more effective than treatment as usual alone. Implications of these findings for the role of game-based meditation interventions for traumatized adolescents in residential care are discussed

Illustrative white matter fiber bundles

Diffusion Tensor Imaging (DTI) has made feasible the visualization of the fibrous structure of the brain whitematter. In the last decades, several fiber-tracking methods have been developed to reconstruct the fiber tracts fromDTI data. Usually these fiber tracts are shown individually based on some selection criteria like region of interest.However, if the white matter as a whole is being visualized clutter is generated by directly rendering the individualfiber tracts. Often users are actually interested in fiber bundles, anatomically meaningful entities that abstractfrom the fibers they contain. Several clustering techniques have been developed that try to group the fiber tractsin fiber bundles. However, even if clustering succeeds, the complex nature of white matter still makes it difficultto investigate. In this paper, we propose the use of illustration techniques to ease the exploration of white matterclusters. We create a technique to visualize an individual cluster as a whole. The amount of fibers visualized forthe cluster is reduced to just a few hint lines, and silhouette and contours are used to improve the definition of thecluster borders. Multiple clusters can be easily visualized by a combination of the single cluster visualizations.Focus+context concepts are used to extend the multiple-cluster renderings. Exploded views ease the explorationof the focus cluster while keeping the context clusters in an abstract form. Real-time results are achieved by theGPU implementation of the presented techniques. Keywords: I.3.3 [Computer Graphics]: Picture/Image Generation—Bitmap and framebuffer operations, Display algorithms, Viewing algorithms

Effectiveness of game-based meditation therapy on neurobiological stress systems in adolescents with posttraumatic symptoms: a randomized controlled trial

Many adolescents in residential care have experienced traumatic events and suffer from posttraumatic stress. Prolonged activation of neurobiological stress systems as the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis can result in long-lasting maladaptive alternations. This study investigated the effectiveness of Muse, a game-based meditation intervention, on the sympathetic nervous system (SNS), parasympathetic nervous system (PNS), and cortisol basal activity and reactivity to acute stress among adolescents with posttraumatic symptoms in residential care. The intervention consisted of two gameplay sessions a week, for 6 consecutive weeks. Seventy-seven adolescents with clinical levels of posttraumatic symptoms (10–18 years old) received either Muse as an addition to treatment as usual (n = 40) or treatment as usual alone (n = 37). We expected reduced basal activity for the SNS and cortisol and increased basal activity for the PNS. As for the response to acute stress, we expected decreased PNS and increased HPA axis reactivity. The Muse group exhibited lower basal activity for the SNS and increased HPA reactivity to acute stress. There were no differences between conditions on SNS and HPA axis activity during rest and on SNS and PNS reactivity to acute stress. Game-based meditation therapy is a promising intervention for the treatment of adolescents with posttraumatic symptoms in residential care. Implications for clinical relevance and trauma-focused treatment purposes are discussed

Motor learning strategies in basketball players and its implications for ACL injury prevention: a randomized controlled trial

Adding external focus of attention (EF, focus on the movement effect) may optimize current anterior cruciate ligament (ACL) injury prevention programmes. The purpose of the current study was to investigate the effects of an EF, by a visual stimulus and an internal focus, by a verbal stimulus during unexpected sidestep cutting in female and male athletes and how these effects remained over time. Ninety experienced basketball athletes performed sidestep cutting manoeuvres in three sessions (S1, S2 and S3). In this randomized controlled trial, athletes were allocated to three groups: visual (VIS), verbal (VER) and control (CTRL). Kinematics and kinetics were collected at the time of peak knee frontal plane moment. Males in the VIS group showed a larger vertical ground reaction force (S1: 25.4 +/- 3.1 N/kg, S2: 25.8 +/- 2.9 N/kg, S3: 25.2 +/- 3.2 N/kg) and knee flexion moments (S1: -3.8 +/- 0.9 Nm/kg, S2: -4.0 +/- 1.2 Nm/kg, S3: -3.9 +/- 1.3 Nm/kg) compared to the males in the VER and CTRL groups and to the females in the VIS group (p <0.05). Additionally, the males in the VIS group reduced knee valgus moment and the females in the VER group reduced knee varus moment over time (n.s.). Male subjects clearly benefit from visual feedback. Females may need different feedback modes to learn a correct movement pattern. Sex-specific learning preferences may have to be acknowledged in day by day practice. Adding video instruction or feedback to regular training regimens when teaching athletes safe movement patterns and providing individual feedback might target suboptimal long-term results and optimize ACL injury prevention programmes. I