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Postgraduate medical education is an essential societal enterprise that prepares highly skilled physicians for the health workforce. In recent years, PGME systems have been criticized worldwide for problems with variable graduate abilities, concerns about patient safety, and issues with teaching and assessment methods. In response, competency based medical education approaches, with an emphasis on graduate outcomes, have been proposed as the direction for 21st century health profession education. However, there are few published models of large-scale implementation of these approaches. We describe the rationale and design for a national, time-variable competency-based multi-specialty system for postgraduate medical education called Competence by Design. Fourteen innovations were bundled to create this new system, using the Van Melle Core Components of competency based medical education as the basis for the transformation. The successful execution of this transformational training system shows competency based medical education can be implemented at scale. The lessons learned in the early implementation of Competence by Design can inform competency based medical education innovation efforts across professions worldwide., Competing Interests: JRF, JK, LSS, FB, VN, ST, JF, KH, RST were employees of the Royal College.JS, AA, AO, AKH, LC, SD, DR, WJC, RBC, TD, BT, LF, WG, ND, BW, RS, RA, DD, AB, MG, and EVM performed contract work for the Royal College., (Copyright: © 2024 The Author(s).)

Transformative changes in health professions education need to incorporate effective faculty development, but few very large-scale faculty development designs have been described. The Royal College of Physicians and Surgeons of Canada's Competence by Design project was launched to transform the delivery of postgraduate medical education in Canada using a competency-based model. In this paper we outline the goals, principles, and rationale of the Royal College's national strategy for faculty and resident development initiatives to support the implementation of Competence by Design. We describe the activities and resources for both faculty and trainees that facilitated the redesign of training programs for each specialty and subspecialty at the national level, as well as supporting the implementation of the redesign at the local level. This undertaking was not without its challenges: we thus reflect on those challenges, enablers, and the lessons learned, and discuss a continuous quality improvement approach that was taken to iteratively inform the implementation process moving forward., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Abstract Background Despite the high burden of musculoskeletal (MSK) diseases, few generalists are comfortable teaching MSK physical examination (PE) skills. Patient Partners® in Arthritis (PP®IA) is a standardized patient educator program that could potentially supplement current MSK PE teaching. This study aims to determine if differences exist in MSK PE skills between non-MSK specialist physician and PP®IA taught students. Methods Pre-clerkship medical students attended 2-hour small group MSK PE teaching by either non-MSK specialist physician tutors or by PP®IA. All students underwent an MSK OSCE and completed retrospective pre-post questionnaires regarding comfort with MSK PE and interest in MSK. Results 83 students completed the OSCE (42 PP®IA, 41 physician taught) and 82 completed the questionnaire (42 PP®IA, 40 physician taught). There were no significant differences between groups in OSCE scores. For all questionnaire items, post-session ratings were significantly higher than pre-session ratings for both groups. In exploratory analysis PP®IA students showed significantly greater improvement in 12 of 22 questions including three of five patient-centred learning questions. Conclusions PP®IA MSK PE teaching is as good as non-MSK specialist physician tutor teaching when measured by a five station OSCE and provide an excellent complementary resource to address current deficits in MSK PE teaching.

Abstract Appendicoliths are commonly found obstructing the lumen of the appendix at the time of appendectomy. To identify factors that might contribute to their formation we investigated the composition of appendicoliths using laser ablation inductively coupled plasma mass spectroscopy, gas chromatography, polarized light microscopy, X-ray crystallography and protein mass spectroscopy. Forty-eight elements, 32 fatty acids and 109 human proteins were identified within the appendicoliths. The most common elements found in appendicoliths are calcium and phosphorus, 11.0 ± 6.0 and 8.2 ± 4.2% weight, respectively. Palmitic acid (29.7%) and stearate (21.3%) are the most common fatty acids. Some stearate is found in crystalline form—identifiable by polarized light microscopy and confirmable by X-ray crystallography. Appendicoliths have an increased ratio of omega-6 to omega-3 fatty acids (ratio 22:1). Analysis of 16 proteins common to the appendicoliths analyzed showed antioxidant activity and neutrophil functions (e.g. activation and degranulation) to be the most highly enriched pathways. Considered together, these preliminary findings suggest oxidative stress may have a role in appendicolith formation. Further research is needed to determine how dietary factors such as omega-6 fatty acids and food additives, redox-active metals and the intestinal microbiome interact with genetic factors to predispose to appendicolith formation.

Edema disease is an often fatal enterotoxemia caused by specific strains of Shiga toxin–producing Escherichia coli (STEC) that affect primarily healthy, rapidly growing nursery pigs. Recently, outbreaks of edema disease have also emerged in France in wild boars. Analysis of STEC strains isolated from wild boars during 2013–2019 showed that they belonged to the serotype O139:H1 and were positive for both Stx2e and F18 fimbriae. However, in contrast to classical STEC O139:H1 strains circulating in pigs, they also possessed enterotoxin genes sta1 and stb, typical of enterotoxigenic E. coli. In addition, the strains contained a unique accessory genome composition and did not harbor antimicrobial-resistance genes, in contrast to domestic pig isolates. These data thus reveal that the emergence of edema disease in wild boars was caused by atypical hybrid of STEC and enterotoxigenic E. coli O139:H1, which so far has been restricted to the wildlife environment.

Abstract Background Type 2 diabetes mellitus (T2DM) is caused by a combination of environmental, genetic, and epigenetic factors including, fasting blood glucose (FBG), genetic variant rs841853, and cg19693031 methylation. We evaluated the interaction between rs841853 and cg19693031 on the FBG levels of non-diabetic Taiwanese adults. Methods We used Taiwan Biobank (TWB) data collected between 2008 and 2016. The TWB data source contains information on basic demographics, personal lifestyles, medical history, methylation, and genotype. The study participants included 1300 people with DNA methylation data. The association of cg19693031 methylation (stratified into quartiles) with rs841853 and FBG was determined using multiple linear regression analysis. The beta-coefficients (β) and p-values were estimated. Results The mean ± standard deviation (SD) of FBG in rs841853-CC individuals (92.07 ± 7.78) did not differ significantly from that in the CA + AA individuals (91.62 ± 7.14). However, the cg19693031 methylation levels were significantly different in the two groups (0.7716 ± 0.05 in CC individuals and 0.7631 ± 0.05 in CA + AA individuals (p = 0.002). The cg19693031 methylation levels according to quartiles were β

Abstract Verbal fluency (VF) is a heterogeneous cognitive function that requires executive as well as language abilities. The purpose of this study was to elucidate the specificity of the resting state MEG correlates of the executive and language components. To this end, we administered a VF test, another verbal test (Vocabulary), and another executive test (Trail Making Test), and we recorded 5-min eyes-open resting-state MEG data in 28 healthy participants. We used source-reconstructed spectral power estimates to compute correlation/anticorrelation MEG clusters with the performance at each test, as well as with the advantage in performance between tests, across individuals using cluster-level statistics in the standard frequency bands. By obtaining conjunction clusters between verbal fluency scores and factor loading obtained for verbal fluency and each of the two other tests, we showed a core of slow clusters (delta to beta) localized in the right hemisphere, in adjacent parts of the premotor, pre-central and post-central cortex in the mid-lateral regions related to executive monitoring. We also found slow parietal clusters bilaterally and a cluster in the gamma 2 and 3 bands in the left inferior frontal gyrus likely associated with phonological processing involved in verbal fluency.

Abstract Infection of hepatocytes by hepatitis B virus (HBV) depends on surface expression of its receptor Na+-taurocholate-cotransporting polypeptide (NTCP), but sufficient NTCP expression is lacking in most cell lines. NTCP can be introduced by plasmid transfection or transduction by viral vectors to render cells permissive for HBV. However, transient transfection of hepatocyte-derived cell lines is inefficient, resulting in inhomogeneous protein expression and does not allow to adapt the level of NTCP expression. We therefore utilized in vitro transcribed mRNA to introduce NTCP into cells. Optimization using alternative cap structures and nucleotide modifications rendered mRNA transfection into different non-hepatic and hepatic cell lines very efficient. After transfection of mRNA, surface expression and functionality of NTCP was demonstrated by staining with an N-terminal HBV-preS peptide and bile acid uptake. Introduction of NTCP by mRNA transfection increased susceptibility of hepatoma cells to HBV in a dose-dependent manner. Transfection of NTCP mRNA into non-liver cells, in contrast, supported bile acid uptake but did still not render the cells permissive for HBV, demonstrating the requirement for additional host factors. Introduction of candidate host factors by mRNA transfection will allow for fast and convenient analysis of the viral life cycle using a transient, but reliable expression system.

# Background This study aimed to evaluate the effectiveness of a Pit Crew intervention to improve team dynamics and time to performance of critical actions in a prehospital critical care scenario. The primary outcome was successful completion of critical actions and time to completion of these critical actions. Secondary outcomes included effectiveness of communication and overall team functioning. # Methods The study was conducted with a fire-based Emergency Medical Services (EMS) system with 233 paramedics and 115 Emergency Medical Technicians (EMT). Eight EMS crews comprised of five members each were randomly selected and assigned to either the intervention or the control group. The intervention group (n=20) watched a thirty-minute video prior to the training describing the “Pit Crew Approach;” the control group (n=20) did not watch the video. Each crew was given the same simulation scenario of a pediatric patient that had overdosed on a beta-blocker. Completion of predetermined critical tasks were noted and timestamped. A survey was administered to the participants following the training to assess team dynamics and level of confidence. # Results Three outcomes were statistically significant between the two arms: The interventional group felt they themselves had a more defined role in the resuscitation in comparison to the non-interventional group (p= 0.021). The interventional group also felt that their team members had a clearer and more defined role than the nonintervention group (p= 0.018). The interventional group also felt more confident managing a beta blocker overdose than the nonintervention group (p.007). The only statistically significant secondary outcome finding was in scene departure decision: the interventional arm spent more time on-scene (p=0.031). Of note, the non-intervention group missed performing tasks more often than the interventional group and team leaders of these groups often performed task(s) while also directing the patient care. # Conclusion The Pit Crew model was developed to optimize communication and team function. Our data identified that a formal instruction of the pit crew approach to a critical care scenario improved comfort in patient care. Future studies are needed evaluate other methods of training and the effects of continued formal pit-crew training over time.

Abstract Background Recently, increased interleukin (IL)-24 expression has been demonstrated in the colon biopsies of adult patients with inflammatory bowel disease (IBD). However, the role of IL-24 in the pathomechanism of IBD is still largely unknown. Methods Presence of IL-24 was determined in the samples of children with IBD and in the colon of dextran sodium sulfate (DSS) treated mice. Effect of inflammatory factors on IL24 expression was determined in peripheral blood (PBMCs) and lamina propria mononuclear cells (LPMCs). Also, the impact of IL-24 was investigated on HT-29 epithelial cells and CCD-18Co colon fibroblasts. Expression of tissue remodeling related genes was investigated in the colon of wild type (WT) mice locally treated with IL-24 and in the colon of DSS treated WT and Il20rb knock out (KO) mice. Results Increased amount of IL-24 was demonstrated in the serum and colon samples of children with IBD and DSS treated mice compared to that of controls. IL-1β, LPS or H2O2 treatment increased the expression of IL24 in PBMCs and LPMCs. IL-24 treatment resulted in increased amount of TGF-β and PDGF-B in HT-29 cells and enhanced the expression of extracellular matrix (ECM)-related genes and the motility of CCD-18Co cells. Similarly, local IL-24 treatment increased the colonic Tgfb1 and Pdgfb expression of WT mice. Moreover, expression of pro-fibrotic Tgfb1 and Pdgfb were lower in the colon of DSS treated Il20rb KO compared to that of WT mice. The disease activity index of colitis was less severe in DSS treated Il20rb KO compared to WT mice. Conclusion Our study suggest that IL-24 may play a significant role in the mucosal remodeling of patients with IBD by promoting pro-fibrotic processes.

Abstract We studied the origin of breaking the symmetry for moving circular contact lines of dewetting polymer films suspended on a periodic array of pillars. There, dewetting force fields driving polymer flow were perturbed by elastic micro-pillars arranged in a regular square pattern. Elastic restoring forces of deformed pillars locally balance driving capillary forces and broke the circular symmetry of expanding dewetting holes. The observed envelope of the dewetting holes reflected the symmetry of the underlying pattern, even at sizes much larger than the characteristic period of the pillar array, demonstrating that periodic perturbations in a driving force field can establish a well-defined pattern of lower symmetry. For the presented system, we succeeded in squaring the circle.

Abstract Background Alcohol consumption is one of the modifiable risk factors for intracerebral hemorrhage, which accounts for approximately 10–20% of all strokes worldwide. We evaluated the association of stroke with genetic polymorphisms in the alcohol metabolizing genes, alcohol dehydrogenase 1B (ADH1B, rs1229984) and aldehyde dehydrogenase 2 (ALDH2, rs671) genes based on alcohol consumption. Methods Data were available for 19,500 Taiwan Biobank (TWB) participants. We used logistic regression models to test for associations between genetic variants and stroke. Overall, there were 890 individuals with ischemic stroke, 70 with hemorrhagic stroke, and 16,837 control individuals. Participants with ischemic but not hemorrhagic stroke were older than their control individuals (mean ± SE, 58.47 ± 8.17 vs. 48.33 ± 10.90 years, p

Abstract Transcranial, minimally-invasive stimulation of the primary motor cortex (M1) has recently emerged to show promise in treating clinically refractory neuropathic pain. However, there is a major need for improving efficacy, reducing variability and understanding mechanisms. Rodent models hold promise in helping to overcome these obstacles. However, there still remains a major divide between clinical and preclinical studies with respect to stimulation programs, analysis of pain as a multidimensional sensory-affective-motivational state and lack of focus on chronic phases of established pain. Here, we employed direct transcranial M1 stimulation (M1 tDCS) either as a single 5-day block or recurring blocks of repetitive stimulation over early or chronic phases of peripherally-induced neuropathic pain in mice. We report that repeated blocks of stimulation reverse established neuropathic mechanical allodynia more strongly than a single 5-day regime and also suppress cold allodynia, aversive behavior and anxiety without adversely affecting motor function over a long period. Activity mapping revealed highly selective alterations in the posterior insula, periaqueductal gray subdivisions and superficial spinal laminae in reversal of mechanical allodynia. Our preclinical data reveal multimodal analgesia and improvement in quality of life by multiple blocks of M1 tDCS and uncover underlying brain networks, thus helping promote clinical translation.

Abstract Root water uptake is an essential process for terrestrial plants that strongly affects the spatiotemporal distribution of water in vegetated soil. Fast neutron tomography is a recently established non-invasive imaging technique capable to capture the 3D architecture of root systems in situ and even allows for tracking of three-dimensional water flow in soil and roots. We present an in vivo analysis of local water uptake and transport by roots of soil-grown maize plants—for the first time measured in a three-dimensional time-resolved manner. Using deuterated water as tracer in infiltration experiments, we visualized soil imbibition, local root uptake, and tracked the transport of deuterated water throughout the fibrous root system for a day and night situation. This revealed significant differences in water transport between different root types. The primary root was the preferred water transport path in the 13-days-old plants while seminal roots of comparable size and length contributed little to plant water supply. The results underline the unique potential of fast neutron tomography to provide time-resolved 3D in vivo information on the water uptake and transport dynamics of plant root systems, thus contributing to a better understanding of the complex interactions of plant, soil and water.

Abstract Developing compact ion accelerators using intense lasers is a very active area of research, motivated by a strong applicative potential in science, industry and healthcare. However, proposed applications in medical therapy, as well as in nuclear and particle physics demand a strict control of ion energy, as well as of the angular and spectral distribution of ion beam, beyond the intrinsic limitations of the several acceleration mechanisms explored so far. Here we report on the production of highly collimated ( $$\sim 0.2^{\circ }$$ ∼ 0 . 2 ∘ half angle divergence), high-charge (10s of pC) and quasi-monoenergetic proton beams up to $$\sim$$ ∼ 50 MeV, using a recently developed method based on helical coil targetry. In this concept, ions accelerated from a laser-irradiated foil are post-accelerated and conditioned in a helical structure positioned at the rear of the foil. The pencil beam of protons was produced by guided post-acceleration at a rate of $$\sim$$ ∼ 2 GeV/m, without sacrificing the excellent beam emittance of the laser-driven proton beams. 3D particle tracing simulations indicate the possibility of sustaining high acceleration gradients over extended helical coil lengths, thus maximising the gain from such miniature accelerating modules.

Abstract In a high-speed single-molecule experiment with a force probe, a protein is tethered between two substrates that are manipulated to exert force on the system. To avoid nonspecific interactions between the protein and nearby substrates, the protein is usually attached to the substrates through long, flexible linkers. This approach precludes measurements of mechanical properties with high spatial and temporal resolution, for rapidly exerted forces are dissipated into the linkers. Because mammalian hearing operates at frequencies reaching tens to hundreds of kilohertz, the mechanical processes that occur during transduction are of very short duration. Single-molecule experiments on the relevant proteins therefore cannot involve long tethers. We previously characterized the mechanical properties of protocadherin 15 (PCDH15), a protein essential for human hearing, by tethering an individual monomer through very short linkers between a probe bead held in an optical trap and a pedestal bead immobilized on a glass coverslip. Because the two confining surfaces were separated by only the length of the tethered protein, hydrodynamic coupling between those surfaces complicated the interpretation of the data. To facilitate our experiments, we characterize here the anisotropic and position-dependent diffusion coefficient of a probe in the presence of an effectively infinite wall, the coverslip, and of the immobile pedestal.

Unlike other European domesticates introduced in the Americas after the European invasion, equids (Equidae) were previously in the Western Hemisphere but were extinct by the late Holocene era. The return of equids to the Americas through the introduction of the domestic horse (Equus caballus) is documented in the historical literature but is not explored fully either archaeologically or genetically. Historical documents suggest that the first domestic horses were brought from the Iberian Peninsula to the Caribbean in the late 15th century CE, but archaeological remains of these early introductions are rare. This paper presents the mitochondrial genome of a late 16th century horse from the Spanish colonial site of Puerto Real (northern Haiti). It represents the earliest complete mitogenome of a post-Columbian domestic horse in the Western Hemisphere offering a unique opportunity to clarify the phylogeographic history of this species in the Americas. Our data supports the hypothesis of an Iberian origin for this early translocated individual and clarifies its phylogenetic relationship with modern breeds in the Americas.

BackgroundThe purpose of this article is to illustrate the application of an evidence-based, structured performance measurement methodology to identify, prioritize, and (when appropriate) generate new measures of health care quality, using primary care as a case example. Primary health care is central to the health care system and health of the American public; thus, ensuring high quality is essential. Due to its complexity, ensuring high-quality primary care requires measurement frameworks that can assess the quality of the infrastructure, workforce configurations, and processes available. This paper describes the use of the Productivity Measurement and Enhancement System (ProMES) to compile a targeted set of such measures, prioritized according to their contribution and value to primary care.MethodsWe adapted ProMES to select and rank existing primary care measures according to value to the primary care clinic. Nine subject matter experts (SMEs) consisting of clinicians, hospital leaders and national policymakers participated in facilitated expert elicitation sessions to identify objectives of performance, corresponding measures, and priority rankings.ResultsThe SMEs identified three fundamental objectives: access, patient-health care team partnerships, and technical quality. The SMEs also selected sixteen performance indicators from the 44 pre-vetted, currently existing measures from three different data sources for primary care. One indicator, Team 2-Day Post Discharge Contact Ratio, was selected as an indicator of both team partnerships and technical quality. Indicators were prioritized according to value using the contingency functions developed by the SMEs.ConclusionOur article provides an actionable guide to applying ProMES, which can be adapted to the needs of various industries, including measure selection and modification from existing data sources, and proposing new measures. Future work should address both logistical considerations (e.g., data capture, common data/programming language) and lingering measurement challenges, such as operationalizating measures to be meaningful and interpretable across health care settings.

BackgroundFollowing the full re-opening of schools in England and emergence of the SARS-CoV-2 Alpha variant, we investigated the risk of SARS-CoV-2 infection in students and staff who were contacts of a confirmed case in a school bubble (school groupings with limited interactions), along with their household members.MethodsPrimary and secondary school bubbles were recruited into sKIDsBUBBLE after being sent home to self-isolate following a confirmed case of COVID-19 in the bubble. Bubble participants and their household members were sent home-testing kits comprising nasal swabs for RT-PCR testing and whole genome sequencing, and oral fluid swabs for SARS-CoV-2 antibodies.ResultsDuring November-December 2020, 14 bubbles were recruited from 7 schools, including 269 bubble contacts (248 students, 21 staff) and 823 household contacts (524 adults, 299 children). The secondary attack rate was 10.0% (6/60) in primary and 3.9% (4/102) in secondary school students, compared to 6.3% (1/16) and 0% (0/1) among staff, respectively. The incidence rate for household contacts of primary school students was 6.6% (12/183) and 3.7% (1/27) for household contacts of primary school staff. In secondary schools, this was 3.5% (11/317) and 0% (0/1), respectively. Household contacts were more likely to test positive if their bubble contact tested positive although there were new infections among household contacts of uninfected bubble contacts.InterpretationCompared to other institutional settings, the overall risk of secondary infection in school bubbles and their household contacts was low. Our findings are important for developing evidence-based infection prevention guidelines for educational settings.

Introduction In the field of arthroscopic rotator cuff repair (ARCR), reporting standards of published studies differ dramatically, notably concerning adverse events (AEs). In addition, prognostic studies are overall methodologically poor, based on small data sets and explore only limited numbers of influencing factors. We aim to develop prognostic models for individual ARCR patients, primarily for the patient-reported assessment of shoulder function (Oxford Shoulder Score (OSS)) and the occurrence of shoulder stiffness 6 months after surgery. We also aim to evaluate the use of a consensus core event set (CES) for AEs and validate a severity classification for these events, considering the patient’s perspective.Methods and analysis A cohort of 970 primary ARCR patients will be prospectively documented from several Swiss and German orthopaedic clinics up to 24 months postoperatively. Patient clinical examinations at 6 and 12 months will include shoulder range of motion and strength (Constant Score). Tendon repair integrity status will be assessed by ultrasound at 12 months. Patient-reported questionnaires at 6, 12 and 24 months will determine functional scores (subjective shoulder value, OSS), anxiety and depression scores, working status, sports activities, and quality of life (European Quality of Life 5 Dimensions 5 Level questionnaire). AEs will be documented according to a CES. Prognostic models will be developed using an internationally supported regression methodology. Multiple prognostic factors, including patient baseline demographics, psychological, socioeconomic and clinical factors, rotator cuff integrity, concomitant local findings, and (post)operative management factors, will be investigated.Ethics and dissemination This project contributes to the development of personalised risk predictions for supporting the surgical decision process in ARCR. The consensus CES may become an international reference for the reporting of complications in clinical studies and registries. Ethical approval was obtained on 1 April 2020 from the lead ethics committee (EKNZ, Basel, Switzerland; ID: 2019-02076). All participants will provide informed written consent before enrolment in the study.Trial registration number NCT04321005.Protocol version Version 2 (13 December 2019).

This research compares and evaluates different approaches to approximate offense times of crimes. It contributes to and extends all previously proposed naïve and aoristic temporal approximation methods and one recent study [1] that showed that the addition of historical crimes with accurately known time stamps to temporal approximation methods can outperform all traditional approximation methods. It is paramount to work with crime data that possess precise temporal information to conduct reliable (spatiotemporal) analysis and modeling. This study contributes to and extends existing studies on temporal analysis. One novel and one relatively new temporal approximation methods are introduced that rely on weighting aoristic scores with historic offenses with exactly known offense times. It is hypothesized that these methods enhance the accuracy of the temporal approximation. In total, eight different methods are evaluated for apartment burglaries in Vienna, Austria, for yearly and seasonal differences. Results show that the one novel and one relatively new method applied in this research outperform all other existing approximation methods to estimate and predict offense times. These two methods are particularly useful for both researchers and practitioners, who often work with temporally imprecise crime data.

Technological developments in recent decades have increased young people's engagement with screen-based technologies (screen time), and a reduction in young people's contact with nature (green time) has been observed concurrently. This combination of high screen time and low green time may affect mental health and well-being. The aim of this systematic scoping review was to collate evidence assessing associations between screen time, green time, and psychological outcomes (including mental health, cognitive functioning, and academic achievement) for young children (

Dietary specialization, exploiting a small fraction of available food resources, is commonly reported for gulls and skuas. Predation of birds by these species is usually considered a specialist strategy employed by the minority of the population but non-specialists also predate birds and may actually have a greater impact on the prey species. To date, most studies have focused on predatory bird-specialists, down-playing the possible importance of opportunistic predation by non-specialists. We addressed this by studying diet (regurgitated pellets and prey remains) and behavior of breeding Herring Gulls (Larus argentatus) over three summers at Gull Island, a mixed-species breeding colony in Lake Ontario. One-third of all pellets analyzed contained bird remains, primarily the most numerous breeding bird: Ring-billed Gull (L. delawarensis) chicks (51%) and adults (36%). Although all but one pair of Herring Gulls ate birds, all pairs maintained broad and mostly similar diets, with birds accounting for at most one-third of prey. Behavior also indicated that Herring Gulls at Gull Island were not predatory bird-specialists because predation was too infrequent to meet energetic requirements, was largely unsuccessful and was only ever observed when Ring-billed Gulls strayed into Herring Gull breeding territories. Instead, bird predation appeared mainly opportunistic, increasing with seasonal availability, access to shoreline, proximity to nesting Ring-billed Gulls and breeding territory size. Compared with predatory specialist Herring Gulls in the same region, individuals that predated birds at Gull Island did not display specialist behaviors and killed six times fewer birds (0.1-0.4 per day, on average) but were over 20 times more numerous (98% of the population versus 4%). Thus, our results indicate that opportunistic predation by non-specialists may have important consequences for prey species. Since opportunistic predation cannot be effectively managed using techniques widely advocated for specialist predators, it is essential to investigate cause of predation by large gulls prior to lethal management.

BackgroundResearch addressing perceptions of housing in people with Parkinson's disease (PD) is rare, and existing instruments capturing perceived aspects of housing are rarely used. Perceived housing comprises of several domains and is associated with health in general older populations. One such domain is meaning of home, captured by the Meaning of Home Questionnaire (MOH). The aim of this study was to evaluate psychometric properties of the MOH among people with PD.Materials and methodsThe MOH was administrated to 245 participants with PD (mean age = 69.9 years; mean PD duration = 9.7 years). The instrument consisted of four sub-scales with 28 items, each with 11 response options (strongly disagree = 0; strongly agree = 10). We evaluated data quality, structural validity (factor analysis), construct validity (i.e., testing correlations with relevant constructs according to pre-defined hypotheses), corrected item total correlations, floor and ceiling effects and internal consistency.ResultsThe data quality was high (0-1.2% missing data). The exploratory factor analysis suggested removal of five items and revealed three new factors; "My home is my castle", "My home is my prison" and "My home is my social hub". The 23-item MOH showed statistically significant correlations with life satisfaction, usability and ADL dependence, while not correlated with number of environmental barriers. These findings were largely as hypothesised, thus supporting construct validity (both convergent and discriminant). The corrected item total correlations were >0.3 for all items and the internal consistency was >0.70 for all sub-scales. No floor or ceiling effects were reported except for the sub-scale "My home is my castle" (ceiling effect = 15.6%).ConclusionsThe 23-item MOH version with three new sub-scales is sufficiently reliable and valid for use in PD populations. This paves the way for further research of meaning of home among people with PD, using the 23-item MOH version.

Electrophoretic deposition (EPD) is a material processing technology which uses direct current (DC) voltage to deposit thin layers on a metallic substrate. EPD is a promising coating technology for medical devices due to its advantages such as thin homogenous layers and a broad range of usable substrates. The objective of this paper is to demonstrate how EPD can be deployed successfully to apply an insulation layer on a stimulation electrode. The Mapping suction probe by inomed Medizintechnik GmbH, Germany, was coated in this investigation. The unique feature of this product is that it combines both a surgical vacuum and a stimulation probe and is used for brain tumour resection. As for the insulation layer, ethylene chlorotrifluoroethylene (ECTFE) was chosen because of its good dielectric and biocompatible properties. ECTFE particles (Halar®6514, Solvay Specialty Polymer, Italy) were mixed with a solvent (Novec™ 7100DL Engineered Fluid, 3M™) to form a suspension. The coating process was partly automatized to ensure good repeatability and reproducibility. For coating, the stimulation probe was immersed in the suspension so that the counter electrode, a stainless-steel net, surrounded it equidistantly. A heat treatment of the coated device in an oven (FED56, Binder, Germany) was required afterwards to melt the deposited polymer particles. After the heat treatment, a glossy black layer (layer thickness 42 μm) was observed on the substrate. A smooth and homogenous surface confirmed that the coating is suitable for surgical application. However, due to a high evaporation rate of the solvent, the ratio of particles and solvent changes and the coating process will have to be controlled in the future to achieve a stable process. Further advantages of EPD such as short processing time, straightforward process flow and scalability enables high production quantities which is attractive for industrial application. EPD might be a promising coating technology for medical devices in the future.

Abstract Nitrous acid (HONO) is an important precursor of the hydroxyl radical (OH), the atmosphere´s primary oxidant. An unknown strong daytime source of HONO is required to explain measurements in ambient air. Emissions from soils are one of the potential sources. Ammonia-oxidizing bacteria (AOB) have been identified as possible producers of these HONO soil emissions. However, the mechanisms for production and release of HONO in soils are not fully understood. In this study, we used a dynamic soil-chamber system to provide direct evidence that gaseous emissions from nitrifying pure cultures contain hydroxylamine (NH2OH), which is subsequently converted to HONO in a heterogeneous reaction with water vapor on glass bead surfaces. In addition to different AOB species, we found release of HONO also in ammonia-oxidizing archaea (AOA), suggesting that these globally abundant microbes may also contribute to the formation of atmospheric HONO and consequently OH. Since biogenic NH2OH is formed by diverse organisms, such as AOB, AOA, methane-oxidizing bacteria, heterotrophic nitrifiers, and fungi, we argue that HONO emission from soil is not restricted to the nitrifying bacteria, but is also promoted by nitrifying members of the domains Archaea and Eukarya.

Abstract The few data available on fusarenon-X (FX) do not support the derivation of health-based guidance values, although preliminary results suggest higher toxicity than other regulated trichothecenes. Using histo-morphological analysis and whole transcriptome profiling, this study was designed to obtain a global view of the intestinal alterations induced by FX. Deoxynivalenol (DON) served as a benchmark. FX induced more severe histological alterations than DON. Inflammation was the hallmark of the molecular toxicity of both mycotoxins. The benchmark doses for the up-regulation of key inflammatory genes by FX were 4- to 45-fold higher than the previously reported values for DON. The transcriptome analysis revealed that both mycotoxins down-regulated the peroxisome proliferator-activated receptor (PPAR) and liver X receptor - retinoid X receptor (LXR-RXR) signaling pathways that control lipid metabolism. Interestingly, several pathways, including VDR/RXR activation, ephrin receptor signaling, and GNRH signaling, were specific to FX and thus discriminated the transcriptomic fingerprints of the two mycotoxins. These results demonstrate that FX induces more potent intestinal inflammation than DON. Moreover, although the mechanisms of toxicity of both mycotoxins are similar in many ways, this study emphasize specific pathways targeted by each mycotoxin, highlighting the need for specific mechanism-based risk assessments of Fusarium mycotoxins.

Abstract Water infiltration in soil is not only affected by the inherent heterogeneities of soil, but even more by the interaction with plant roots and their water uptake. Neutron tomography is a unique non-invasive 3D tool to visualize plant root systems together with the soil water distribution in situ. So far, acquisition times in the range of hours have been the major limitation for imaging 3D water dynamics. Implementing an alternative acquisition procedure we boosted the speed of acquisition capturing an entire tomogram within 10 s. This allows, for the first time, tracking of a water front ascending in a rooted soil column upon infiltration of deuterated water time-resolved in 3D. Image quality and resolution could be sustained to a level allowing for capturing the root system in high detail. Good signal-to-noise ratio and contrast were the key to visualize dynamic changes in water content and to localize the root uptake. We demonstrated the ability of ultra-fast tomography to quantitatively image quick changes of water content in the rhizosphere and outlined the value of such imaging data for 3D water uptake modelling. The presented method paves the way for time-resolved studies of various 3D flow and transport phenomena in porous systems.

Abstract Organotypic, three-dimensional (3D) cancer models have enabled investigations of complex microtissues in increasingly realistic conditions. However, a drawback of these advanced models remains the poor biological relevance of cancer cell lines, while higher clinical significance would be obtainable with patient-derived cell cultures. Here, we describe the generation and data analysis of 3D microtissue models from patient-derived xenografts (PDX) of non-small cell lung carcinoma (NSCLC). Standard of care anti-cancer drugs were applied and the altered multicellular morphologies were captured by confocal microscopy, followed by automated image analyses to quantitatively measure phenotypic features for high-content chemosensitivity tests. The obtained image data were thresholded using a local entropy filter after which the image foreground was split into local regions, for a supervised classification into tumor or fibroblast cell types. Robust statistical methods were applied to evaluate treatment effects on growth and morphology. Both novel and existing computational approaches were compared at each step, while prioritizing high experimental throughput. Docetaxel was found to be the most effective drug that blocked both tumor growth and invasion. These effects were also validated in PDX tumors in vivo. Our research opens new avenues for high-content drug screening based on patient-derived cell cultures, and for personalized chemosensitivity testing.

Abstract Potato (Solanum tuberosum) is an important staple crop worldwide, it has been cultivated in the Andean Altiplano under low-input farming practices at high altitudes and under harsh environment for centuries. We analyzed secondary metabolite (SM) gene diversity encoded in the potato rhizosphere microbiome during plant growth at three distinct sites located in the Andes at high altitudes by 454-pyrosequencing of non-ribosomal peptide and polyketide biosynthetic genes. Phylogenetic analysis indicated that the majority of rhizosphere SM-encoding sequences differed from previously known sequences and may have distinct ancestors. In particular, actinobacterial methyl-malonyl-CoA transferase and acyl carrier protein from Firmicutes, both involved in the synthesis of SMs, showed widespread distribution of clades which were clearly distinct from sequences deposited in public databases, and only 11% of these sequences could be linked to the production of specific classes of SMs. Although the same cultivar was analyzed, SM gene composition radically differed among plant growth stages and across sites, suggesting a distinct repertoire of SM genes that likely encode diverse SM structures. Also, great diversity of non-ribosomal peptide and polyketide biosynthetic pathways in potato-associated microbiomes in the Andean highlands may represent a rich source of novel natural products.

Introduction Lung cancer is a leading cause of cancer deaths worldwide and surgery remains the main treatment for early stage disease. Prior to the introduction of video-assisted thoracoscopic surgery (VATS), lung resection for cancer was undertaken through an open thoracotomy. To date, the evidence base supporting the different surgical approaches is based on non-randomised studies, small randomised trials and is focused mainly on short-term in-hospital outcomes.Methods and analysis The VIdeo assisted thoracoscopic lobectomy versus conventional Open LobEcTomy for lung cancer study is a UK multicentre parallel group randomised controlled trial (RCT) with blinding of outcome assessors and participants (to hospital discharge) comparing the effectiveness, cost-effectiveness and acceptability of VATS lobectomy versus open lobectomy for treatment of lung cancer. We will test the hypothesis that VATS lobectomy is superior to open lobectomy with respect to self-reported physical function 5 weeks after randomisation (approximately 1 month after surgery). Secondary outcomes include assessment of efficacy (hospital stay, pain, proportion and time to uptake of chemotherapy), measures of safety (adverse health events), oncological outcomes (proportion of patients upstaged to pathologic N2 (pN2) disease and disease-free survival), overall survival and health related quality of life to 1 year. The QuinteT Recruitment Intervention is integrated into the trial to optimise recruitment.Ethics and dissemination This trial has been approved by the UK (Dulwich) National Research Ethics Service Committee London. Findings will be written-up as methodology papers for conference presentation, and publication in peer-reviewed journals. Many aspects of the feasibility work will inform surgical RCTs in general and these will be reported at methodology meetings. We will also link with lung cancer clinical studies groups. The patient and public involvement group that works with the Respiratory Biomedical Research Unit at the Brompton Hospital will help identify how we can best publicise the findings.Trial registration number ISRCTN13472721

BACKGROUND In Switzerland, complementary medicine (CM) is officially recognised within the healthcare system and mainly practised in an integrative manner, in conjunction with conventional medicine. As in other countries, there is high demand for and use of CM with children. However, there has so far been no research into the attitude towards, training in and offer of CM among paediatricians in Switzerland. Our study addresses this gap by investigating these topics with an online survey of paediatricians in Switzerland. METHODS We conducted a national online survey using a 19-item, self-reporting questionnaire among all ordinary and junior members of the Swiss Society of Paediatrics (SSP). A comparison of the study sample with the population of all paediatricians registered with the Swiss Medical Association (FMH) allowed an assessment of the survey’s representativeness. The data analysis was performed on the overall group level as well as for predefined subgroups (e.g. sex, age, language, workplace and professional experience). RESULTS 1890 paediatricians were approached and 640, from all parts of Switzerland, responded to the survey (response rate 34%). Two thirds of respondents were female, were aged between 35 and 55 years, trained as paediatric generalist and worked in a practice. Apart from young paediatricians in training, the study sample was representative of all Swiss paediatricians. 23% had attended training in CM, most frequently in phytotherapy, homeopathy, acupuncture/traditional Chinese medicine (TCM) and anthroposophic medicine. 65% were interested in CM courses and training. 16% provide CM services to their patients and almost all paediatricians (97%) are asked by patients/parents about CM therapies. More than half of the responding paediatricians use CM for themselves or their families. 42% were willing to contribute to paediatric CM research. CONCLUSIONS In a representative sample of paediatricians in Switzerland, their personal attitude towards CM is positive, emphasised by great interest in CM training, a willingness to contribute to CM research and a high rate of paediatricians who use CM for themselves and their families. In contrast, the percentage of paediatricians offering CM is currently rather low despite strong demand for CM for children. This study provides key pointers for the future development of complementary and integrative medicine for children in Switzerland.

Motivational intensity has been previously linked to information processing. In particular, it has been argued that affects which are high in motivational intensity tend to narrow cognitive scope. A similar effect has been attributed to negative affect, which has been linked to narrowing of cognitive scope. In this paper, we investigated how these phenomena manifest themselves during visual word search. We conducted three studies in which participants were instructed to perform word category identification. We manipulated motivational intensity by controlling reward expectations and affect via reward outcomes. Importantly, we altered visual search paradigms, assessing the effects of affective manipulations as modulated by information arrangement. We recorded multiple physiological signals (EEG, EDA, ECG and eye tracking) to assess whether motivational states can be predicted by physiology. Across the three studies, we found that high motivational intensity narrowed visual attentional scope by altering visual search strategies, especially when information was displayed sparsely. Instead, when information was vertically listed, approach-directed motivational intensity appeared to improve memory encoding. We also observed that physiology, in particular eye tracking, may be used to detect biases induced by motivational intensity, especially when information is sparsely organised.

BACKGROUND:Outcome of type 2 diabetes care depends on the acceptance of self-responsibility by informed patients, as treatment goals will otherwise be missed. AIMS AND METHODS:This pre/post-observational report describes the clinical outcome of type 2 diabetes care in patients with type 2 diabetes (N =930) admitted consecutively to a diabetes rehabilitation clinic (DRC) between June 2013, and June 2016, where they were exposed to standardized lifestyle modification with meals low in salt and rich in vegetables and fruits, totaling 1,200 to 1,600 kcal/d, and an add-on exercise load equivalent to 400-600 kcal/d. RESULTS:At admission, patients presented with multiple treatment modes, elevated HbA1c levels (7.6±1.5%, 60±16 mmol/mol), a high prevalence of co-morbidities dominated by obesity (79%), a low rate of influenza and pneumococcal immunization (

Febrile illness is a major burden in African children, and non-malarial causes of fever are uncertain. In this retrospective exploratory study, we used metagenomic next-generation sequencing (mNGS) to evaluate serum, nasopharyngeal, and stool specimens from 94 children (aged 2-54 months) with febrile illness admitted to Tororo District Hospital, Uganda. The most common microbes identified were Plasmodium falciparum (51.1% of samples) and parvovirus B19 (4.4%) from serum; human rhinoviruses A and C (40%), respiratory syncytial virus (10%), and human herpesvirus 5 (10%) from nasopharyngeal swabs; and rotavirus A (50% of those with diarrhea) from stool. We also report the near complete genome of a highly divergent orthobunyavirus, tentatively named Nyangole virus, identified from the serum of a child diagnosed with malaria and pneumonia, a Bwamba orthobunyavirus in the nasopharynx of a child with rash and sepsis, and the genomes of two novel human rhinovirus C species. In this retrospective exploratory study, mNGS identified multiple potential pathogens, including 3 new viral species, associated with fever in Ugandan children.