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Objectives To compare paediatric healthcare practice variation among five European emergency departments (EDs) by analysing variability in decisions about diagnostic testing, treatment and admission.Design and population Consecutive paediatric visits in five European EDs in four countries (Austria, Netherlands, Portugal, UK) were prospectively collected during a study period of 9–36 months (2012–2015).Primary outcome measures Practice variation was studied for the following management measures: lab testing, imaging, administration of intravenous medication and patient disposition after assessment at the ED.Analysis Multivariable logistic regression was used to adjust for general patient characteristics and markers of disease severity. To assess whether ED was significantly associated with management, the goodness-of-fit of regression models based on all variables with and without ED as explanatory variable was compared. Management measures were analysed across different categories of presenting complaints.Results Data from 111 922 children were included, with a median age of 4 years (IQR 1.7–9.4). There were large differences in frequencies of Manchester Triage System (MTS) urgency and selected MTS presentational flow charts. ED was a significant covariate for management measures. The variability in management among EDs was fairly consistent across different presenting complaints after adjustment for confounders. Adjusted OR (aOR) for laboratory testing were consistently higher in one hospital while aOR for imaging were consistently higher in another hospital. Iv administration of medication and fluids and admission was significantly more likely in two other hospitals, compared with others, for most presenting complaints.Conclusions Distinctive hospital-specific patterns in variability of management could be observed in these five paediatric EDs, which were consistent across different groups of clinical presentations. This could indicate fundamental differences in paediatric healthcare practice, influenced by differences in factors such as organisation of primary care, diagnostic facilities and available beds, professional culture and patient expectations.

Abstract Background Human cardiac stem cells expressing the W8B2 marker (W8B2+ CSCs) were recently identified and proposed as a new model of multipotent CSCs capable of differentiating into smooth muscle cells, endothelial cells and immature myocytes. Nevertheless, no characterization of ion channel or calcium activity during the differentiation of these stem cells has been reported. Methods The objectives of this study were thus to analyze (using the TaqMan Low-Density Array technique) the gene profile of W8B2+ CSCs pertaining to the regulation of ion channels, transporters and other players involved in the calcium homeostasis of these cells. We also analyzed spontaneous calcium activity (via the GCaMP calcium probe) during the in vitro differentiation of W8B2+ CSCs into cardiac myocytes. Results Our results show an entirely different electrophysiological genomic profile between W8B2+ CSCs before and after differentiation. Some specific nodal genes, such as Tbx3, HCN, ICaT, L, KV, and NCX, are overexpressed after this differentiation. In addition, we reveal spontaneous calcium activity or a calcium clock whose kinetics change during the differentiation process. A pharmacological study carried out on differentiated W8B2+ CSCs showed that the NCX exchanger and IP3 stores play a fundamental role in the generation of these calcium oscillations. Conclusions Taken together, the present results provide important information on ion channel expression and intrinsic calcium dynamics during the differentiation process of stem cells expressing the W8B2 marker.

Abstract The Companion Vector-Borne Diseases (CVBD) World Forum is a working group of leading international experts who meet annually to evaluate current scientific findings and future trends concerning the distribution, pathogenesis, clinical presentation, diagnosis and prevention of vector-borne infections of dogs and cats. At the 14th Symposium of the CVBD World Forum in Trieste, Italy (March 25–28, 2019), we identified the need to (i) bring attention to the potential spread of parasites and vectors with relocated dogs, and (ii) provide advice to the veterinary profession regarding the importance of surveillance and treatment for parasites and vector-borne infections when rehoming dogs. This letter shares a consensus statement from the CVBD World Forum as well as a summary of the problem faced, including the role of veterinary professionals in parasite surveillance, causal issues, and the importance of interdisciplinary cooperation in addressing the problem. To limit opportunities for dissemination of parasites and vectors, whenever possible, underlying problems creating the need for dog rehoming should be addressed. However, when it is necessary to rehome dogs, this should ideally take place in the country and national region of origin. When geographically distant relocation occurs, veterinary professionals have a vital role to play in public education, vigilance for detection of exotic vectors and infections, and alerting the medical community to the risk(s) for pathogen spread. With appropriate veterinary intervention, dog welfare needs can be met without inadvertently allowing global spread of parasites and their vectors.

Abstract Background Individuals with co-occurring hyperactivity disorder/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) can have complex presentations that may complicate diagnosis and treatment. There are established guidelines with regard to the identification and treatment of ADHD and ASD as independent conditions. However, ADHD and ASD were not formally recognised diagnostically as co-occurring conditions until the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) was published in 2013. Hence, awareness and understanding of both conditions when they co-occur is less established and there is little guidance in the clinical literature. This has led to uncertainty among healthcare practitioners when working with children, young people and adults who present with co-existing ADHD and ASD. The United Kingdom ADHD Partnership (UKAP) therefore convened a meeting of professional experts that aimed to address this gap and reach expert consensus on the topic that will aid healthcare practitioners and allied professionals when working with this complex and vulnerable population. Method UK experts from multiple disciplines in the fields of ADHD and ASD convened in London in December 2017. The meeting provided the opportunity to address the complexities of ADHD and ASD as a co-occurring presentation from different perspectives and included presentations, discussion and group work. The authors considered the clinical challenges of working with this complex group of individuals, producing a consensus for a unified approach when working with male and female, children, adolescents and adults with co-occurring ADHD and ASD. This was written up, circulated and endorsed by all authors. Results The authors reached a consensus of practical recommendations for working across the lifespan with males and females with ADHD and ASD. Consensus was reached on topics of (1) identification and assessment using rating scales, clinical diagnostic interviews and objective supporting assessments; outcomes of assessment, including standards of clinical reporting; (2) non-pharmacological interventions and care management, including psychoeducation, carer interventions/carer training, behavioural/environmental and Cognitive Behavioural Therapy (CBT) approaches; and multi-agency liaison, including educational interventions, career advice, occupational skills and training, and (3) pharmacological treatments. Conclusions The guidance and practice recommendations (Tables 1, 4, 5, 7, 8 and 10) will support healthcare practitioners and allied professionals to meet the needs of this complex group from a multidisciplinary perspective. Further research is needed to enhance our understanding of the diagnosis, treatment and management of individuals presenting with comorbid ADHD and ASD.

Macrophages are critical in limiting replication of herpes simplex virus type 1 (HSV-1). Here the authors show how acid ceramidase and its enzymatic product sphingosine enable multivesicular bodies to function as an anti-viral mechanism.

Background Achieving robust responses with adoptive cell therapy for the treatment of the highly lethal pancreatic ductal adenocarcinoma (PDA) has been elusive. We previously showed that T cells engineered to express a mesothelin-specific T cell receptor (TCRMsln) accumulate in autochthonous PDA, mediate therapeutic antitumor activity, but fail to eradicate tumors in part due to acquisition of a dysfunctional exhausted T cell state.Methods Here, we investigated the role of immune checkpoints in mediating TCR engineered T cell dysfunction in a genetically engineered PDA mouse model. The fate of engineered T cells that were either deficient in PD-1, or transferred concurrent with antibodies blocking PD-L1 and/or additional immune checkpoints, were tracked to evaluate persistence, functionality, and antitumor activity at day 8 and day 28 post infusion. We performed RNAseq on engineered T cells isolated from tumors and compared differentially expressed genes to prototypical endogenous exhausted T cells.Results PD-L1 pathway blockade and/or simultaneous blockade of multiple coinhibitory receptors during adoptive cell therapy was insufficient to prevent engineered T cell dysfunction in autochthonous PDA yet resulted in subclinical activity in the lung, without enhancing anti-tumor immunity. Gene expression analysis revealed that ex vivo TCR engineered T cells markedly differed from in vivo primed endogenous effector T cells which can respond to immune checkpoint inhibitors. Early after transfer, intratumoral TCR engineered T cells acquired a similar molecular program to prototypical exhausted T cells that arise during chronic viral infection, but the molecular programs later diverged. Intratumoral engineered T cells exhibited decreased effector and cell cycle genes and were refractory to TCR signaling.Conclusions Abrogation of PD-1 signaling is not sufficient to overcome TCR engineered T cell dysfunction in PDA. Our study suggests that contributions by both the differentiation pathways induced during the ex vivo T cell engineering process and intratumoral suppressive mechanisms render engineered T cells dysfunctional and resistant to rescue by blockade of immune checkpoints.

Objectives Compare lay expectations of medical development to those of experts in the context of SARS-CoV-2 vaccine development. Methods A short online survey of experts and lay people measuring when participants believe important vaccine milestones would occur and how likely potential setbacks were. Samples of US and Canadian lay people recruited through Qualtrics. The expert sample was created through a contact network in vaccine development and supplemented with corresponding authors of recent scholarly review articles on vaccine development. Results In aggregate, lay people gave responses that were within 3 months of experts, tending to be later than experts for early milestones and earlier for later milestones. Median lay best estimates for when a vaccine would be available to the public were 08/2021 and 09/2021 for the US and Canadian samples, compared with 09-10/2021 for the experts. However, many individual lay responses showed more substantial disagreement with expert opinions, with 54% of lay best estimates of when a vaccine would be available to the public being before the median expert soonest estimate or after the median expert latest estimate. Lay people were much more pessimistic about vaccine development encountering setbacks than experts (median probability 59% of boxed warning compared with only 30% for experts). Misalignment between layperson and expert expectations was not explained by any demographic variables collected in our survey. Conclusion Median lay expectations were generally similar to experts. At the individual level, however, lay people showed substantial variation with many believing milestones would occur much sooner than experts. Lay people were in general much more pessimistic about the prospect of setbacks than were experts.

Abstract Background Foot involvement is a major manifestation of psoriatic arthritis (PsA) and can lead to severe levels of foot pain and disability and impaired functional mobility and quality of life. Gait spatiotemporal parameters (STPs) and gait variability, used as a clinical index of gait stability, have been associated with several adverse health outcomes, including risk of falling, functional decline, and mortality in a wide range of populations. Previous studies showed some alterations in STPs in people with PsA. However, gait variability and the relationships between STPs, gait variability and self‐reported foot pain and disability have never been studied in these populations. Body‐worn inertial measurement units (IMUs) are gaining interest in measuring gait parameters in clinical settings. Objectives To assess STPs and gait variability in people with PsA using IMUs, to explore their relationship with self‐reported foot pain and function and to investigate the feasibility of using IMUs to discriminate patient groups based on gait speed‐critical values. Methods Twenty‐one participants with PsA (age: 53.9 ± 8.9 yrs.; median disease duration: 6 yrs) and 21 age‐ and sex‐matched healthy participants (age 54.23 ± 9.3 yrs) were recruited. All the participants performed three 10‐m walk test trials at their comfortable speed. STPs and gait variability were recorded and calculated using six body‐worn IMUs and Mobility Lab software (APDM®). Foot pain and disability were assessed in participants with PsA using the foot function index (FFI). Results Cadence, gait speed, stride length, and swing phase were significantly lower, while double support was significantly higher, in the PsA group (p 0.57, p

Conserved IncI1 and IncHI1 plasmids carrying blaCTX-M-1 have been found circulating in chickens and horses from continental Europe, respectively. In Canada, blaCTX-M-1 is overwhelmingly the most common blaCTX-M variant found in Escherichia coli from chicken and horses and can be recovered at lower frequencies in swine, cattle, and dogs. Whole-genome sequencing has identified a large genetic diversity of isolates carrying this variant, warranting further investigations into the plasmids carrying this gene. Therefore, the objective of this study was to describe the genetic profiles of blaCTX-M-1 plasmids circulating in E. coli from Canadian domestic animals and compare them to those recovered in animals in Europe. Fifty-one blaCTX-M-1 positive E. coli isolates from chicken (n = 14), horses (racetrack horses n = 11; community horses n = 3), swine (n = 7), turkey (n = 6), dogs (n = 5), beef cattle (n = 3), and dairy cattle (n = 2) were selected for plasmid characterization. Sequences were obtained through both Illumina and Oxford Nanopore technologies. Genomes were assembled using either Unicycler hybrid assembly or Flye with polishing performed using Pilon. blaCTX-M-1 was found residing on a plasmid in 45 isolates and chromosomally located in six isolates. A conserved IncI1/ST3 plasmid was identified among chicken (n = 12), turkey (n = 4), swine (n = 6), dog (n = 2), and beef cattle (n = 2) isolates. When compared against publicly available data, these plasmids showed a high degree of similarity to those identified in isolates from poultry and swine in Europe. These results suggest that an epidemic IncI1/ST3 plasmid similar to the one found in Europe is contributing to the spread of blaCTX-M-1 in Canada. A conserved IncHI1/FIA(HI1)/ST2 plasmid was also recovered from nearly all racetrack horse isolates (n = 10). Although IncHI1/ST2 plasmids have been reported among European horse isolates, IncHI1/ST9 plasmids appear to be more widespread. Further studies are necessary to understand the factors contributing to these plasmids’ success in their respective populations.

Tuberous sclerosis complex is a rare genetic multisystem condition that is associated with a high prevalence of neurodevelopmental disorders such as autism and attention-deficit/hyperactivity disorder. The underlying neural mechanisms of the emergence of these symptom domains in tuberous sclerosis complex remain unclear.Here, we use fixel-based analysis of diffusion-weighted imaging, which allows for the differentiation between multiple fibre populations within a voxel, to compare white matter properties in 16 participants with tuberous sclerosis complex (aged 11–19) and 12 age and sex matched control participants. We further tested associations between white matter alterations and autism and inattention symptoms as well as cognitive ability in participants with tuberous sclerosis complex.Compared to controls, participants with tuberous sclerosis complex showed reduced fibre density cross-section (FDC) in the dorsal branch of right superior longitudinal fasciculus and bilateral inferior longitudinal fasciculus, reduced fibre density (FD) in bilateral tapetum, and reduced fibre cross-section (FC) in the ventral branch of right superior longitudinal fasciculus. In participants with tuberous sclerosis complex, the extent of FDC reductions in right superior longitudinal fasciculus was significantly associated with autism traits (social communication difficulties and restricted, repetitive behaviours), whereas FDC reductions in right inferior longitudinal fasciculus were associated with inattention. The observed white matter alterations were unrelated to cognitive ability.Our findings shed light on the fibre-specific biophysical properties of white matter alterations in tuberous sclerosis complex and suggest that these regional changes are selectively associated with the severity of neurodevelopmental symptoms.

The development of an ideal vascular prosthesis represents an important challenge in terms of the treatment of cardiovascular diseases with respect to which new materials are being considered that have produced promising results following testing in animal models. This study focuses on nanofibrous polycaprolactone-based grafts assessed by means of histological techniques 10 days and 6 months following suturing as a replacement for the rat aorta. A novel stereological approach for the assessment of cellular distribution within the graft thickness was developed. The cellularization of the thickness of the graft was found to be homogeneous after 10 days and to have changed after 6 months, at which time the majority of cells was discovered in the inner layer where the regeneration of the vessel wall was found to have occurred. Six months following implantation, the endothelialization of the graft lumen was complete, and no vasa vasorum were found to be present. Newly formed tissue resembling native elastic arteries with concentric layers composed of smooth muscle cells, collagen, and elastin was found in the implanted polycaprolactone-based grafts. Moreover, the inner layer of the graft was seen to have developed structural similarities to the regular aortic wall. The grafts appeared to be well tolerated, and no severe adverse reaction was recorded with the exception of one case of cartilaginous metaplasia close to the junctional suture.

Gait assessment is of interest to clinicians and researchers because it provides information about patients’ functional mobility. Optoelectronic camera-based systems with gait event detection algorithms are considered the gold standard for gait assessment. Yet, the choice of the algorithm used to process data and extract the desired parameters from those detected gait events has an impact on the validity and reliability of the gait parameters computed. There are multiple techniques documented in the literature for computing gait events, including the analysis of the minimal position of the heel and toe markers, the computation of the relative distance between sacrum and foot markers, and the assessment of the smallest distance between the heel and toe markers. Validation studies conducted on these algorithms report variations in accuracy. Yet, these studies were conducted in different conditions, at varying gait velocities, and on different populations. The purpose of this study is to compare accuracy, precision, and robustness of three algorithms using motion capture data obtained from 25 healthy persons and 21 psoriatic arthritic patients walking at three distinct speeds on an instrumented treadmill. Errors in gait events recognition (heel strike—HS and toe-off—TO) and their impact on gait metrics (stance phase and stride length) are reported and compared to ground reaction force events measured with force plates. Over the 9114 collected steps across all walking speeds, more than 99% of gait events were recognized by all algorithms. On average, HS events were detected within 1.2 ms of the reference for two algorithms, while the third one detected HS late, with an average detection error of 40.7 ms. Yet, significant variations in accuracy were noted with gait speed; the performance decreased for all algorithms at slow speed. TO events were identified early by all algorithms, with an average error ranging from 16.0 to 100.0 ms. These gait events errors lead to 2–15% inaccuracies in stance phase assessment, while the impact on stride length remains below 0.3 cm. Overall, the algorithm based on the relative distance between the sacral and foot markers stood out for its accuracy, precision, and robustness at all walking speeds.

Abstract Background Although keeping small poultry flocks is increasingly popular in Ontario, information on the antimicrobial susceptibility of enteric bacteria of such flocks is lacking. The current study was conducted on small poultry flocks in Ontario between October 2015 and September 2017, and samples were submitted on a voluntary basis to Ontario’s Animal Health Laboratory. From each submission, a pooled cecal sample was obtained from all the birds of the same species from the same flock and tested for the presence of two common enteric pathogens, E. coli and Salmonella. Three different isolates from each E. coli-positive sample and one isolate from each Salmonella-positive sample were selected and tested for susceptibility to 14 antimicrobials using a broth microdilution technique. Results A total of 433 fecal E. coli isolates (358 chicken, 27 turkey, 24 duck, and 24 game bird) and 5 Salmonella isolates (3 chicken, 1 turkey, and 1 duck) were recovered. One hundred and sixty-seven chicken, 5 turkey, 14 duck, and 15 game bird E. coli isolates were pan-susceptible. For E. coli, a moderate to high proportion of isolates were resistant to tetracycline (43% chicken, 81% turkey, 42% duck, and 38% game bird isolates), streptomycin (29% chicken, 37% turkey, and 33% game bird isolates), sulfonamides (17% chicken, 37% turkey, and 21% duck isolates), and ampicillin (16% chicken and 41% turkey isolates). Multidrug resistance was found in 37% of turkey, 20% of chicken, 13% of duck, and 8% of game bird E. coli isolates. Salmonella isolates were most frequently resistant to streptomycin, tetracycline, and sulfonamides. Resistance to cephalosporins, carbapenems, macrolides, and quinolones was infrequent in both E. coli and Salmonella isolates. Cluster and correlation analyses identified streptomycin-tetracycline-sulfisoxazole-trimethoprim-sulfamethoxazole as the most common resistance pattern in chicken E. coli isolates. Turkey E. coli isolates compared to all the other poultry species had higher odds of resistance to tetracycline and ampicillin, and a higher multidrug resistance rate. Conclusions Escherichia coli isolates were frequently resistant to antimicrobials commonly used to treat poultry bacterial infections, which highlights the necessity of judicious antimicrobial use to limit the emergence of multidrug resistant bacteria.

Abstract Background The ongoing Syrian civil war has led to massive population displacements, leading to the reorganization of the asylum policies of several countries. Accordingly, like other European countries, the Swiss government has recently chosen to implement a specific resettlement program. This program is characterized by the fact that the whole nuclear family is granted a work and residence permit upon arrival, and benefits from enhanced integration services. The aim of the present project is to evaluate the effects of the Swiss resettlement program, with a special focus on mental health, while adopting a family perspective. Methods The outcomes of 15 Syrian families taking part in this program will be compared to those of 15 Syrian families that came to Switzerland through other means (i.e., following the usual asylum procedure, which is much more stressful and time consuming). Each family member above 8 years old will be invited to participate to a 3-wave longitudinal survey concerning the resettlement process: upon arrival in the collective shelters, six and 12 months later. Questionnaires will be used for the evaluation of participants’ mental health, risk behaviors, general health, romantic relationship, parent-child relationship, family functioning, parentification, social support, and social identities related to group belongingness. Discussion The findings of the present project will provide longitudinal information on Syrian refugees. A comprehensive approach will be adopted by screening potential difficulties that the sample may be faced with and potential strengths that participants may rely on. Accordingly, physical and mental health, as well as the quality of family functioning, the feeling of support and of belongingness to different groups will be evaluated. We will also compare the results of families who had the chance to immigrate through the Swiss resettlement program, to the results of families that did not. This comparison will allow the elaboration of hypotheses regarding adjusted asylum policies. Furthermore, it will enhance our knowledge regarding the impact of displacement on the family system. Indeed, although the role of the family for the well-being of adults and children has been established, surprisingly few studies have adopted this focus in the asylum field.

Dogs are the main reservoir of Leishmania infantum and in some countries have been regularly culled as part of government policy to control visceral leishmaniasis. At the 13th Symposium of the Companion Vector-Borne Diseases World Forum in Windsor, UK, March 19–22, 2018, we consolidated a consensus statement regarding the usefulness of dog culling as a means of controlling visceral leishmaniasis. The statement highlighted the futility of culling infected dogs, whether healthy or sick, as a measure to control the domestic reservoir of L. infantum and reduce the risk for visceral leishmaniasis.

Background Rib fractures are common among trauma patients and may result in significant morbidity and mortality. There are numerous treatment options, but ideal management is unclear. Delivery of local anesthetic via an analgesia catheter for continuous intercostal nerve blockade offers an attractive potential option for management of patients with rib fractures.Methods We performed a single-center, retrospective case–control analysis of trauma patients with multiple rib fractures from 2016 to 2018, comparing patients managed with continuous intercostal nerve blockade with standard care. Matching was performed in a 2:1 ratio by Injury Severity Score, age, and gender. Respiratory morbidity potentially secondary to rib fractures, including unplanned intubation, failure of extubation, need for tracheostomy, pneumonia, or mortality, were all identified and included. Potential complications due to catheter insertion were identified to be recorded. The primary outcome of interest was 30-day hospital-free days.Results Nine hundred and thirty-three patients were eligible for analysis, with 48 managed using intercostal blockade compared with 96 matching controls. No complications of intercostal blockade were identified during the study period. Controls demonstrated fewer rib fractures (6.60±4.11 vs. 9.3±3.73, p=0.001) and fewer flail segments (0.8±1.76 vs. 2.0±2.94, p=0.02). Those managed with intercostal blockade demonstrated significantly more 30-day hospital-free days (15.9±6.43 vs. 13.2±9.94, p=0.048), less incidence of pneumonia (4.2% vs. 16.7%, p=0.03), and lower hospital mortality (2.1% vs. 13.5%, p=0.03). When adjusting for number of rib fractures and number of flail segments, use of continuous intercostal nerve blockade was significantly associated with lower hospital mortality (OR 0.10; 95% CI 0.01 to 0.91), pneumonia (OR 0.15; 95% CI 0.03 to 0.76), or need for tracheostomy (OR 0.23; 95% CI 0.06 to 0.83).Discussion The addition of continuous intercostal nerve blockade may help to improve outcomes in patients with multiple rib fractures compared with standard care alone.Level of evidence Therapeutic/care management; level IV.

Diabetic kidney disease (DKD) is a key microvascular complication of diabetes, with few therapies for targeting renal disease pathogenesis and progression. We performed transcriptional and protein studies on 103 unique blood and kidney tissue samples from patients with and without diabetes to understand the pathophysiology of DKD injury and its progression. The study was based on the use of 3 unique patient cohorts: peripheral blood mononuclear cell (PBMC) transcriptional studies were conducted on 30 patients with DKD with advancing kidney injury; Gene Expression Omnibus (GEO) data was downloaded, containing transcriptional measures from 51 microdissected glomerulous from patients with DKD. Additionally, 12 independent kidney tissue sections from patients with or without DKD were used for validation of target genes in diabetic kidney injury by kidney tissue immunohistochemistry and immunofluorescence. PBMC DKD transcriptional analysis, identified 853 genes (p < 0.05) with increasing expression with progression of albuminuria and kidney injury in patients with diabetes. GEO data was downloaded, normalized, and analyzed for significantly changed genes. Of the 325 significantly up regulated genes in DKD glomerulous (p < 0.05), 28 overlapped in PBMC and diabetic kidney, with perturbed FcER1 signaling as a significantly enriched canonical pathway. FcER1 was validated to be significantly increased in advanced DKD, where it was also seen to be specifically co-expressed in the kidney biopsy with tissue mast cells. In conclusion, we demonstrate how leveraging public and private human transcriptional datasets can discover and validate innate immunity and inflammation as key mechanistic pathways in DKD progression, and uncover FcER1 as a putative new DKD target for rational drug design.

Forgoing healthcare for economic reasons has been previously associated with adverse health outcomes, including a higher risk of hospitalization, a lower quality of life, and worse self-reported health. However, the exact cause-to-effect relation between forgoing healthcare and health-related outcomes has been insufficiently described. Here, we investigate the prospective health consequences of forgoing healthcare for economic reasons using data from “ReBus” (N = 400), a prospective study examining the health consequences of forgoing healthcare (Baseline: 2008–2013, Follow-up: 2014–2016). Using regression models, we explored the baseline determinants of forgoing healthcare, including socioeconomic, demographic, and pre-existing health-risk factors, and examined the associations between forgoing healthcare at baseline and health deterioration at follow-up, using highly pertinent biomarkers (glucose, glycated hemoglobin, lipids, blood pressure) and SF-36 questionnaire data.Low income, low occupation, low education, and smoking were associated with higher odds of forgoing healthcare at baseline. Forgoing healthcare for economic reasons at baseline was subsequently related to detrimental changes in glucose, high-density lipoprotein cholesterol (HDL), and blood pressure (BP) at follow-up, independently of baseline socioeconomic factors (Glucose-β = 0.19, 95%CI[0.03;0.34], HDL-β = -0.07, 95%CI[-0.14;0.01], BP-β = 3.30, 95%CI[-0.01;6.60]). Moreover, we found strong associations between forgoing healthcare and adverse SF-36 health scores at follow-up, with individuals forgoing healthcare systematically displaying worse health scores (6%–11% lower scores).For the first time, we show that forgoing healthcare for economic reasons predicts adverse health-related consequences 2–8 years later. Our findings shall further encourage the implementation of public health measures aimed at identifying individuals who forgo healthcare and preventing the adverse health consequences of unmet medical needs.

The Reproducibility Project: Cancer Biology (RPCB) was established to provide evidence about reproducibility in basic and preclinical cancer research, and to identify the factors that influence reproducibility more generally. In this commentary we address some of the scientific, ethical and policy implications of the project. We liken the basic and preclinical cancer research enterprise to a vast 'diagnostic machine' that is used to determine which clinical hypotheses should be advanced for further development, including clinical trials. The results of the RPCB suggest that this diagnostic machine currently recommends advancing many findings that are not reproducible. While concerning, we believe that more work needs to be done to evaluate the performance of the diagnostic machine. Specifically, we believe three questions remain unanswered: how often does the diagnostic machine correctly recommend against advancing real effects to clinical testing?; what are the relative costs to society of false positive and false negatives?; and how well do scientists and others interpret the outputs of the machine?

Background: Laboratory testing is routinely used to assay blood biomarkers to provide information on physiologic state beyond what clinicians can evaluate from interpreting medical imaging. We hypothesized that deep learning interpretation of echocardiogram videos can provide additional value in understanding disease states and can evaluate common biomarkers results. Methods: We developed EchoNet-Labs, a video-based deep learning algorithm to detect evidence of anemia, elevated B-type natriuretic peptide (BNP), troponin I, and blood urea nitrogen (BUN), as well as values of ten additional lab tests directly from echocardiograms. We included patients (n = 39,460) aged 18 years or older with one or more apical-4-chamber echocardiogram videos (n = 70,066) from Stanford Healthcare for training and internal testing of EchoNet-Lab's performance in estimating the most proximal biomarker result. Without fine-tuning, the performance of EchoNet-Labs was further evaluated on an additional external test dataset (n = 1,301) from Cedars-Sinai Medical Center. We calculated the area under the curve (AUC) of the receiver operating characteristic curve for the internal and external test datasets. Findings: On the held-out test set of Stanford patients not previously seen during model training, EchoNet-Labs achieved an AUC of 0.80 (0.79-0.81) in detecting anemia (low hemoglobin), 0.86 (0.85-0.88) in detecting elevated BNP, 0.75 (0.73-0.78) in detecting elevated troponin I, and 0.74 (0.72-0.76) in detecting elevated BUN. On the external test dataset from Cedars-Sinai, EchoNet-Labs achieved an AUC of 0.80 (0.77-0.82) in detecting anemia, of 0.82 (0.79-0.84) in detecting elevated BNP, of 0.75 (0.72-0.78) in detecting elevated troponin I, and of 0.69 (0.66-0.71) in detecting elevated BUN. We further demonstrate the utility of the model in detecting abnormalities in 10 additional lab tests. We investigate the features necessary for EchoNet-Labs to make successful detection and identify potential mechanisms for each biomarker using well-known and novel explainability techniques. Interpretation: These results show that deep learning applied to diagnostic imaging can provide additional clinical value and identify phenotypic information beyond current imaging interpretation methods. Funding: J.W.H. and B.H. are supported by the NSF Graduate Research Fellowship. D.O. is supported by NIH K99 HL157421-01. J.Y.Z. is supported by NSF CAREER 1942926, NIH R21 MD012867-01, NIH P30AG059307 and by a Chan-Zuckerberg Biohub Fellowship.

COVID-19 caused major changes in private and public arenas. Individuals were forced to reorganise their daily lives in response to the restrictive measures imposed by governments. The redistribution of gender roles and the responsibility for care provides an example of the reconfigurations that took place during the pandemic. This article sheds light on the implications of the pandemic for gender inequalities by exploring how care work was reconfigured as women and men sought to protect family members and navigated risks of infection. The study is based on qualitative data – interviews and observations – gathered in an interdisciplinary medical anthropology project. In the article, the authors focus on seven cases selected from a larger corpus to illustrate how reconfigurations of the gendered division of care work within families shifted during the pandemic as men assumed greater moral responsibility for safeguarding family members, without infringing the norms of masculinity. The first part of the article explores the intensification of care activities during lockdown for women living in the Canton de Vaud in Switzerland. The second part centres on the moral responsibility and duty for women and men to protect family members from viral exposure. The results from the study confirm not only that most care activities continued to be delegated to female family members, but also that men’s roles evolved. While their safeguarding role can be understood as a new form of caring for men, the findings suggest that it was essentially crisis specific and did not challenge masculinity norms. The extent to which this reconfiguration of gender roles might have a longer-term impact on gender inequalities remains to be seen. Meanwhile, these observations could have important implications for policies aimed at mitigating the medium and long-term effects of the pandemic on gender inequality.

Cytomegalovirus (CMV) viremia continues to cause significant morbidity and mortality in kidney transplant patients with clinical complications including organ rejection and death. Whole blood gene expression dynamics in CMV viremic patients from onset of DNAemia through convalescence has not been well studied to date in humans. To evaluate how CMV infection impacts whole blood leukocyte gene expression over time, we evaluated a matched cohort of 62 kidney transplant recipients with and without CMV DNAemia using blood samples collected at multiple time points during the 12-month period after transplant. While transcriptomic differences were minimal at baseline between DNAemic and non-DNAemic patients, hundreds of genes were differentially expressed at the long-term timepoint, including genes enriching for pathways important for macrophages, interferon, and IL-8 signaling. Amongst patients with CMV DNAemia, the greatest amount of transcriptomic change occurred between baseline and 1-week post-DNAemia, with increase in pathways for interferon signaling and cytotoxic T cell function. Time-course gene set analysis of these differentially expressed genes revealed that most of the enriched pathways had a significant time-trend. While many pathways that were significantly down- or upregulated at 1 week returned to baseline-like levels, we noted that several pathways important in adaptive and innate cell function remained upregulated at the long-term timepoint after resolution of CMV DNAemia. Differential expression analysis and time-course gene set analysis revealed the dynamics of genes and pathways involved in the immune response to CMV DNAemia in kidney transplant patients. Understanding transcriptional changes caused by CMV DNAemia may identify the mechanism behind patient vulnerability to CMV reactivation and increased risk of rejection in transplant recipients and suggest protective strategies to counter the negative immunologic impact of CMV. These findings provide a framework to identify immune correlates for risk assessment and guiding need for extending antiviral prophylaxis.

The wave of migration that has hit Europe in recent years has led to several changes in the organization of asylum systems and medical care provided to migrants. Previous studies indicate that asylum seekers and refugees face multiple barriers in accessing health care. For that reason, adapted structures are needed. In this context, a family consultation service was implemented in our medical center in Lausanne, Switzerland. It aimed at addressing the unique health care needs of recently resettled families from Syria, which has been the leading source country for refugees since 2014. This intervention, developed through collaboration between the University Center for Primary Care and Public Health (Unisanté) and the Children's Hospital of Lausanne (HEL) involved a multidisciplinary team comprising a pediatrician, a general practitioner and a pediatric nurse. Bringing together a multidisciplinary team optimized care coordination, facilitated communication between care providers and enabled a more global vision of the family system with the aim of enhancing quality of care.

No artigo, analisamos o uso das mídias digitais por Linn da Quebrada, artista dissidente em termos de gênero, sexualidade, raça e classe social. Linn se identifica enquanto bixa, preta, ora travesti, ora transexual e “da quebrada”, tendo conquistado certa visibilidade midiática a partir da publicação de produções audiovisuais no YouTube. A abordagem metodológica consistiu em etnografia digital por perambulação, na qual percorremos os fluxos de relações constituídas pela artista a partir do uso do YouTube, nos anos de 2016 e 2017, visando refletir sobre os engajamentos performativos que ela adotou em plataformas digitais. Também demonstramos como a emergência da artista se dá a partir da problematização das normas de gênero e sexualidade, em momento de acirramento do debate político sobre essas mesmas no país e da consolidação de uma configuração midiática altamente segmentada em uma sociedade digital.

The threat of diseases varies considerably among individuals, and it has been found to be linked to various proactive or reactive behaviors. In the present studies, we investigated the impact of individual differences in the perceived vulnerability to disease (PVD) on social touch before (Study 1) or during the coronavirus disease 2019 (COVID-19) pandemic (Study 2). We also investigated the influence of personality traits in the covariation between these two dimensions. We found that people who are the most disease-avoidant are also the most reluctant to touching or being touched by others (and this relationship holds when personality traits are taken into account). Interestingly, the association between PVD and social touch increased during the COVID-19 pandemic compared with a few months before. By showing that the fear of contamination has an association with social touch , the findings provide further evidence for the behavioral immune system ( Schaller and Park, 2011 ), a psychological system acting as a first line of defense against pathogens.

Political ontology reveals the processes of domination at play in the enactment of realities in a(post-) colonial context. In this article, we illustrate the implications of the power asymmetries inherent in conservation and co-management of protected areas involving Indigenous populations. We do so by exploring the case of Pilón Lajas in the Bolivian Amazon region, an area with double legal status as an Indigenous Territory and Biosphere Reserve. Drawing from our ethnographic fieldwork, we describe how indigenous relational ontology and the modern ontology of 'cultural diversity' are enacted by different stakeholders, and analyse critically the problems that arise for protected area management owing to the domination of a single ontology in a context where different ontologies are enacted. We finish by presenting our argument that solving such problems requires a cognitive justice approach.

Sinds het einde van de vorige eeuw houden mediahistorici zich meer bezig met de manier waarop media-inhoud tot stand is gekomen en welke betekenis dat heeft gehad voor publieksgroepen en maatschappelijk-politieke realiteiten. In dit artikel wordt gepoogd deze benadering te combineren met digital history, aan de hand van het verzuilingsdebat en gebruik makend van de digitale krantencollectie van de Koninklijke Bibliotheek van Nederland. Enerzijds wordt onderzocht in hoeverre de veronderstelde ideologische gebondenheid van dagbladen in de jaren 1918-1967 zichtbaar wordt in de hoeveelheid kopij waarmee katholieke en sociaaldemocratische kranten over politiek hebben bericht en hoe verschillen daarin te verklaren zijn. Anderzijds wordt door het testen van kwantitatieve methoden uit de digital humanities geprobeerd een bijdrage te leveren aan digitale bronnenkritiek voor historisch onderzoek. Since the end of the last century media historians have taken an interest in researching the origins and development of media content and its significance for audiences and socio-political realities. This article seeks to combine this approach with digital history. It does so by focusing on the pillarisation debate and by utilising the digital newspaper collection of the National Library of the Netherlands. On the one hand, this article investigates to what extent the ideological background of the Catholic and Social Democratic press is actually reflected in the number of newspaper articles reporting on politics written between 1918-1967, and how any differences can be explained. On the other hand, by testing quantitative methods from the digital humanities, the article attempts to contribute to digital source criticism for historical research.

The microbiome has been implicated in the development of metabolic conditions which occur at high rates in people with schizophrenia and related psychoses. This exploratory proof-of-concept study aimed to: (i) characterize the gut microbiota in antipsychotic naïve or quasi-naïve people with first-episode psychosis, and people with established schizophrenia receiving clozapine therapy; (ii) test for microbiome changes following a lifestyle intervention which included diet and exercise education and physical activity. Participants were recruited from the Eastern Suburbs Mental Health Service, Sydney, Australia. Anthropometric, lifestyle and gut microbiota data were collected at baseline and following a 12-week lifestyle intervention. Stool samples underwent 16S rRNA sequencing to analyse microbiota diversity and composition. Seventeen people with established schizophrenia and five people with first-episode psychosis were recruited and matched with 22 age-sex, BMI and ethnicity matched controls from a concurrent study for baseline comparisons. There was no difference in α-diversity between groups at baseline, but microbial composition differed by 21 taxa between the established schizophrenia group and controls. In people with established illness pre-post comparison of α-diversity showed significant increases after the 12-week lifestyle intervention. This pilot study adds to the current literature that detail compositional differences in the gut microbiota of people with schizophrenia compared to those without mental illness and suggests that lifestyle interventions may increase gut microbial diversity in patients with established illness. These results show that microbiome studies are feasible in patients with established schizophrenia and larger studies are warranted to validate microbial signatures and understand the relevance of lifestyle change in the development of metabolic conditions in this population.

Nonalcoholic steatohepatitis (NASH) increases with fructose consumption and metabolic syndrome and has been recently linked with endogenous ethanol production, notably by high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn). Candida yeasts are the main causes of auto-brewery syndromes but have been neglected in NASH. Here, the fecal ethanol and microbial content of 10 cases and 10 controls were compared. Ethanol was measured by gas chromatography-mass spectrometry. Species identification was performed by MALDI-TOF MS, and triglyceride production was assessed by a colorimetric enzymatic assay. The fecal ethanol concentration was four times higher in patients with NASH (median [interquartile range]: 0.13 [0.05–1.43] vs. 0.034 [0.008–0.57], p = 0.037). Yeasts were isolated from almost all cases but not from controls (9/10 vs. 0/10, p = 0.0001). Pichia kudriavzevii was the most frequent (four patients), while Candida glabrata, Candida albicans, and Galactomyces geotrichum were identified in two cases each. The concentration of ethanol produced by yeasts was 10 times higher than that produced by bacteria (median, 3.36 [0.49–5.60] vs. 0.32 [0.009–0.43], p = 0.0029). Using a 10% D-fructose restricted medium, we showed that NASH-associated yeasts transformed fructose in ethanol. Unexpectedly, yeasts isolated from NASH patients produced a substantial amount of triglycerides. Pichia kudriavzevii strains produced the maximal ethanol and triglyceride levels in vitro. Our preliminary human descriptive and in vitro experimental results suggest that yeasts have been neglected. In addition to K. pneumoniae, gut Pichia and Candida yeasts could be linked with NASH pathophysiology in a species- and strain-specific manner through fructose-dependent endogenous alcohol and triglyceride production.

Imaging the marine environment is more and more useful to understand relationships between species, as well as natural processes. Developing photogrammetry allowed the use of 3D measuring to study populations dynamics of sessile organisms at various scales: from colony to population. This study focuses on red coral (Corallium rubrum), as known as precious coral. Metrics measured at a colony scale (e.g., maximum height, diameter and number of branches) allowed population understanding and a comparison between an old (Cerbère-Banyuls reserve) vs. a new (Calanques National Park) MPA. Our results suggested a 5-year time step allows the appearance of a significant difference between populations inside vs. outside the Calanques National Park no-take zones. Red coral colonies were taller and had more branches inside no-take zones. A significant difference was still observable for the populations inside the Cerbère-Banyuls reserve after 40 years of protection, reflecting the sustainability and effectiveness of precautionary measures set by the reserve. The impacts at the local level (mechanical destruction) and those presumed to occur via global change (climatic variations) underline the need to develop strategies both to follow the evolutions of red coral populations but also to understand their resilience. Photogrammetry induced modeling is a time and cost effective as well as non-invasive method which could be used to understand population dynamics at a seascape scale on coralligenous reefs.

Frequent users of emergency departments (FUED; ≥ 5 ED visits/year) commonly cumulate medical, social, and substance use problems requiring complex and sustained care coordination often unavailable in ED. This study aimed to explore ED healthcare providers’ challenges related to FUED care to gain insight into the support and resources required to address FUED complex needs. An online survey was sent to all general adult emergency services within Switzerland (N = 106). Participants were asked to indicate the extent to which they perceived that FUED represented a problem and to describe the main challenges encountered. In total, 208 physicians and nurses from 75 EDs (70.7%) completed the survey. Among the 208 participants, 134 (64%) reported that FUED represented a challenge and 133 described 1 to 5 challenges encountered. A conventional content analysis yielded 4 main categories of perceived challenges. Negative consequences in the ED secondary to FUED’s presence (eg, ED overcrowding, staff helplessness, and fatigue) was the most frequently reported challenge, followed by challenges related to FUEDs’ characteristics (eg, mental health and social problems) leading to healthcare complexity. The third most frequently encountered challenge was related to the ED inappropriateness and inefficiency to address FUEDs’ needs. Finally, challenges related to the lack of FUED healthcare network were the least often mentioned. ED healthcare providers experience a wide range of challenges related to FUED care. These findings suggest that currently EDs nor their staff are equipped to address FUEDs’ complex needs.

Objectives Many interventions have been developed over the years to offer frequent users of the emergency department (FUEDs) better access to quality coordinated healthcare. Despite recognising the role primary care physicians (PCPs) play in FUEDs’ care, to date their perceptions of case management, the most studied intervention, have rarely been assessed. Furthermore, a gap regarding PCPs’ experience of caring for FUEDs persists. Thus, this study aimed to explore PCPs’ perceptions of the care provided to FUEDs in emergency and primary care settings, their views on the local case management team (CMT), and their suggestions to improve FUEDs’ care.Design Qualitative study using in-depth semistructured interviews and inductive thematic analysis.Setting Canton of Vaud, Switzerland.Participants Thirty PCPs participated, 16 in private practice (PP-PCPs) and 14 based at the Lausanne University Centre of General Medicine and Public Health (Unisanté—U-PCPs).Results U-PCPs and PP-PCPs thought that most FUEDs’ emergency department (ED) visits were legitimate, but questioned ED adequacy to meet FUEDs’ needs. Yet, both PCP groups reported encountering many challenges in FUEDs’ care themselves. In this context, PP-PCPs seemed more satisfied of the care they provided to FUEDs than U-PCPs. Generally, U-PCPs seemed to find more value in the CMT to help them care for FUEDs than PP-PCPs. To enhance FUEDs’ care, U-PCPs and PP-PCPs suggested enhancing collaboration with other healthcare providers. U-PCPs also wished to increase their availability, and some PP-PCPs considered outpatient clinics, larger group practices or medical centres most appropriate to handle FUEDs’ needs.Conclusions This study highlights the many challenges PCPs face in caring for FUEDs, that a CM intervention has the potential to mitigate, and provides ways forward in improving FUEDs’ care, including reinforced communication with the CMT and ED physicians, and structural changes to their own way of delivering care to FUEDs.

Large bone defects have always been a big challenge. The use of bone marrow mononuclear cells (BMCs) combined with an osteoconductive scaffold has been proved a good alternative for the treatment of large bone defects. Another autologous source for tissue engineering is platelet rich fibrin (PRF). PRF is a blood concentrate system obtained through a one-step centrifugation. The generated 3D matrix of the PRF clot serves as a reservoir of growth factors. Those growth factors might support the regenerative response of BMC, and therefore the effect of PRF, centrifuged with either high medium (208 g) or low (60 g) relative centrifugation force (RCF) on BMCs was evaluated in vitro in the present study. The two PRF matrices obtained were initially characterized and compared to human serum. Significantly increased concentrations of insulin-like growth factor (IGF), soluble intercellular adhesion molecule-1 (sICAM1) and transforming growth factor (TGF)-β were found in PRF compared to human serum whereas VEGF concentration was not significantly altered. A dose-response study revealed no further activation of BMC’s metabolic activity, if concentration of both PRF matrices exceeded 10% (v/v). Effect of both PRF preparations [10%] on BMC was analyzed after 2, 7, and 14 days in comparison to human serum [10%]. Metabolic activity of BMC increased significantly in all groups on day 14. Furthermore, gene expression of matrix metalloproteinases (MMP)-2, −7, and −9 was significantly stimulated in BMC cultivated with the respective PRF matrices compared to human serum. Apoptotic activity of BMC incubated with PRF was not altered compared to BMC cultivated with serum. In conclusion, PRF could be used as a growth factor delivery system of autologous or allogeneic source with the capability of stimulating cells such as BMC.

Patrick Bond provides a biography of Amin’s work as a global political thinker and leader on the left. From his early days building the Third World Forum and establishing “origins of a South-centric organic intelligentsia with global visions” to his work with the World Social Forum process, Amin dedicated his life to trying to lay the foundations for a Fifth International. Bond notes Amin’s frustration with the extreme fragmentation and limited policy impacts of left struggles. Yet he points out some recent exceptions here in the successes of global South campaigns around the right to water, access to medicines and the right to health, and Via Campesina and MST’s success in building global resistance to corporate land grabbing.

South Africa hosts Africa's most advanced form of the new Blue Economy, named 'Operation Phakisa: Oceans.' In 2014, the McKinsey-designed project was formally launched by now-disgraced President Jacob Zuma with vibrant state and corporate fanfare. Financially, its most important elements were anticipated to come from corporations promoting shipping investments and port infrastructure, a new generation of offshore oil and gas extraction projects and seabed mining. However, these already conflict with underlying capitalist crisis tendencies associated with overaccumulation (overcapacity), globalization and financialization, as they played out through uneven development, commodity price volatility and excessive extraction of resources. Together this metabolic intensification of capital-nature relations can be witnessed when South Africa recently faced the Blue Economy's ecological contradictions: celebrating a massive offshore gas discovery at the same time as awareness rises about extreme coastal weather events, ocean warming and acidification (with profound threats to fast-bleaching coral reefs), sea-level rise, debilitating drought in Africa's main seaside tourist city (Cape Town), and plastic infestation of water bodies, the shoreline and vulnerable marine life. Critics of the capitalist ocean have demanded a greater state commitment to Marine Protected Areas, support for sustainable subsistence fishing and eco-tourism. But they are losing, and so more powerful resistance is needed, focusing on shifting towards post-fossil energy and transport infrastructure, agriculture and spatial planning. Given how climate change has become devastating to vulnerable coastlines – such as central Mozambique's, victim of two of the Southern Hemisphere's most intense cyclones in March-April 2019 – it is essential to better link ocean defence mechanisms to climate activism: global youth Climate Strikes and the direct action approach adopted by the likes of Dakota Access Pipe Line resistance in the US, Extinction Rebellion in Britain, and Ende Gelände in Germany. Today, as the limits to capital's crisis-displacement tactics are becoming more evident, it is the interplay of these top-down and bottom-up processes that will shape the future Blue Economy narrative, giving it either renewed legitimacy, or the kind of illegitimacy already experienced in so much South African resource-centric capitalism. Keywords: Blue Economy, capitalist crisis, Oceans Phakisa, resistance, South Africa

Seven species of eagle breed in France: Golden Eagle (Aquila chrysaetos), Lesser Spotted Eagle (Aquila pomarina), Bonelli’s Eagle (Aquila fasciata), Booted Eagle (Hieraaetus pennatus), Short-toed Eagle (Circaetus gallicus), Osprey (Pandion haliaetus) and White-tailed Eagle (Haliaeetus albicilla). Populations of all species have increased since the beginning of the 2000s and breeding pairs are estimated at: 2500-3300 in 2012 (Short-toed Eagle), 585-810 in 2012 (Booted Eagle), 450-500 in 2012 (Golden Eagle), 80-90 in 2015 (Osprey),33 in 2016 (Bonelli’s Eagle) and 1 each in 2018 (Lesser spotted Eagle and White-tailed Eagle). These two latter species became new breeding species in 2003 and 2011 respectively. Productivity, expressed as fledgling/pair/year, is estimated to be on average 0.57 (Short-toed Eagle), 1.56 (Osprey), 1.18 (Bonelli’s Eagle), 0.82 (Lesser spotted Eagle), 1.1 (White-tailed Eagle) and from 0.26 (min) to 0.70 (max) (Golden Eagle). The main threats to reproduction relate to decreases in habitat quality (resulting from disturbance, habitat loss and wind farms) and the increase of mortality (from power lines, poaching and poisoning).

Actinobacillosis usually is a sporadic infection that affects the tongue in cattle (“wooden tongue”) with possible spread to the digestive tract. Two 4‐year‐old Rouge‐des‐Prés cows from a single French beef herd were referred for chronic (2‐6 months) swelling and cutaneous nodules in the distal hind limbs. In addition to cutaneous signs, physical examination disclosed cachexia, lameness, lymphadenitis of the hind limbs, and pneumonia in both cows. Cytologic examination of direct skin smears was inconclusive, and no parasites were observed in examination of multiple skin scrapings. Histopathological examination of skin and lung biopsy specimens identified chronic, diffuse, severe pyogranulomatous dermatitis, associated with Splendore‐Hoeppli phenomenon and intralesional Gram‐negative bacteria. Cultures from skin, lymph nodes, and lungs (both cows were euthanized for welfare reasons) identified a Pasteurellaceae organism, confirmed as Actinobacillus lignieresii by partial sequencing of the rpoB gene. This report emphasizes that actinobacillosis can appear as a small outbreak in cattle with cutaneous and respiratory signs.

Abstract Background ED overcrowding represents a significant public health problem in developed countries. Frequent users of the emergency departments (FUEDs; reporting 5 or more ED visits in the past year) are often affected by medical, psychological, social, and substance use problems and account for a disproportionately high number of ED visits. Past research indicates that case management (CM) interventions are a promising way to reduce ED overcrowding and improve FUEDs’ quality of life. There is, however, very limited knowledge about how to disseminate and implement this intervention on a large scale to diverse clinical settings, including community hospitals and non-academic centers. This paper describes the protocol of a research project aiming to implement a CM intervention tailored to FUEDs in the public hospitals with ED in the French-speaking region of Switzerland and evaluate both the implementation process and effectiveness of the CM intervention. Methods This research project uses a hybrid study design assessing both implementation and clinical outcomes. The implementation part of the study uses mixed methods a) to describe quantitatively and qualitatively factors that influence the implementation process, and b) to examine implementation effectiveness. The clinical part of the study uses a within-subject design (pre-post intervention) to evaluate participants’ trajectories on clinical variables (e.g., quality of life, ED use) after receiving the CM intervention. We designed the study based on two implementation science frameworks. The Generic Implementation Framework guided the overall research protocol design, whereas the RE-AIM (reach, efficacy, adoption, implementation and maintenance) framework guided the implementation and effectiveness evaluations. Discussion This research project will contribute to implementation science by providing key insights into the processes of implementing CM into broader practice. This research project is also likely to have both clinical and public health implications. Trial registration NCT03641274, Registered 20 August 2018.

Abstract Background Regulatory approval of next generation sequencing (NGS) by the FDA is advancing the use of genomic-based precision medicine for the therapeutic management of cancer as standard care. Recent FDA guidance for the classification of genomic variants based on clinical evidence to aid clinicians in understanding the actionability of identified variants provided by comprehensive NGS panels has also been set forth. In this retrospective analysis, we interpreted and applied the FDA variant classification guidance to comprehensive NGS testing performed for advanced cancer patients and assessed oncologist agreement with NGS test treatment recommendations. Methods NGS comprehensive genomic profiling was performed in a CLIA certified lab (657 completed tests for 646 patients treated at Roswell Park Comprehensive Cancer Center) between June 2016 and June 2017. Physician treatment recommendations made within 120 days post-test were gathered from tested patients’ medical records and classified as targeted therapy, precision medicine clinical trial, immunotherapy, hormonal therapy, chemotherapy/radiation, surgery, transplant, or non-therapeutic (hospice, surveillance, or palliative care). Agreement between NGS test report targeted therapy recommendations based on the FDA variant classification and physician targeted therapy treatment recommendations were evaluated. Results Excluding variants contraindicating targeted therapy (i.e., KRAS or NRAS mutations), at least one variant with FDA level 1 companion diagnostic supporting evidence as the most actionable was identified in 14% of tests, with physicians most frequently recommending targeted therapy (48%) for patients with these results. This stands in contrast to physicians recommending targeted therapy based on test results with FDA level 2 (practice guideline) or FDA level 3 (clinical trial or off label) evidence as the most actionable result (11 and 4%, respectively). Conclusions We found an appropriate “dose-response” relationship between the strength of clinical evidence supporting biomarker-directed targeted therapy based on application of FDA guidance for NGS test variant classification, and subsequent treatment recommendations made by treating physicians. In view of recent changes at FDA, it is paramount to define regulatory grounds and medical policy coverage for NGS testing based on this guidance.

Food processes use different microorganisms, from bacteria to fungi. Yeast strains have been extensively studied, especially Saccharomyces cerevisiae. However, to date, very little is known about the potential beneficial effects of molds on gut health as part of gut microbiota. We undertook a comprehensive characterization of five mold strains, Penicillium camemberti, P. nalgiovense, P. roqueforti, Fusarium domesticum, and Geotrichum candidum used in food processes, on their ability to trigger or protect intestinal inflammation using in vitro human cell models and in vivo susceptibility to sodium dextran sulfate-induced colitis. Comparison of spore adhesion to epithelial cells showed a very wide disparity in results, with F. domesticum and P. roqueforti being the two extremes, with almost no adhesion and 20% adhesion, respectively. Interaction with human immune cells showed mild pro-inflammatory properties of all Penicillium strains and no effect of the others. However, the potential anti-inflammatory abilities detected for G. candidum in vitro were not confirmed in vivo after oral gavage to mice before and during induced colitis. According to the different series of experiments carried out in this study, the impact of the spores of these molds used in food production is limited, with no specific beneficial or harmful effect on the gut.

Abstract Dirofilaria repens is a nematode affecting domestic and wild canids, transmitted by several species of mosquitoes. It usually causes a non-pathogenic subcutaneous infection in dogs and is the principal agent of human dirofilariosis in the Old World. In the last decades, D. repens has increased in prevalence in areas where it has already been reported and its distribution range has expanded into new areas of Europe, representing a paradigmatic example of an emergent pathogen. Despite its emergence and zoonotic impact, D. repens has received less attention by scientists compared to Dirofilaria immitis. In this review we report the recent advances of D. repens infection in dogs and humans, and transmission by vectors, and discuss possible factors that influence the spread and increase of this zoonotic parasite in Europe. There is evidence that D. repens has spread faster than D. immitis from the endemic areas of southern Europe to northern Europe. Climate change affecting mosquito vectors and the facilitation of pet travel seem to have contributed to this expansion; however, in the authors’ opinion, the major factor is likely the rate of undiagnosed dogs continuing to perpetuate the life-cycle of D. repens. Many infected dogs remain undetected due to the subclinical nature of the disease, the lack of rapid and reliable diagnostic tools and the poor knowledge and still low awareness of D. repens in non-endemic areas. Improved diagnostic tools are warranted to bring D. repens diagnosis to the state of D. immitis diagnosis, as well as improved screening of imported dogs and promotion of preventative measures among veterinarians and dog owners. For vector-borne diseases involving pets, veterinarians play a significant role in prevention and should be more aware of their responsibility in reducing the impact of the zoonotic agents. In addition, they should enhance multisectorial collaboration with medical entomologists and the public health experts, under the concept and the actions of One Health-One Medicine.

The article is dedicated to the analysis of centrifugal tendencies within the framework of BRICS and to their influence on the processes, proceeding in the system of global world. Factors, which stimulate these tendencies are examined. The author considers that, in spite of positive potential and the notable position, which the countries of BRICS play under the conditions of global crisis phenomena, by their present economic policy they contribute to the sanitation “of imperialism”; activate the negative manifestations of the global “crisis of capitalism”. In the author’s the opinion multipolarity strengthens the neoliberal nature of institutes, especially in spheres of finances, trade and climate. The corporations, which are based in the countries of BRICS, demonstrate super-exploitation in the course of the accumulation of capital both in their regions and beyond their limits. The article is based on comprehension of documents of international organizations, including UNCTAD, analytics views, sometimes adhering to contrary opinions. The main aim of the author is to prove the possibility to move in positive direction. The article contains the claim to the society of BRICS members to consider summit of BRICS in Johannesburg in 2018 as an invitation for serious discussion of the problems of contemporary global policy.

Abstract Objective To examine the quality of the evidence relied upon by the World Health Organisation (WHO) in promoting hand hygiene with campaigns such as “Save Lives: Clean Your Hands”. Results The quality of evidence in the studies quoted by the WHO evidence document is highly variable and the methods used limited. In some of the quoted studies, hand hygiene was the primary outcome, rather than the clinically significant outcome of hospital acquired infection (HAI). When HAI was the primary outcome, it was often poorly defined and reported with scant detail. There was wide variation in the hand hygiene compliance achieved in the intervention studies. The majority of studies where the intervention was a campaign to promote hand hygiene used historical control data with variable attempts to account for the fact that HAI rates may have been declining prior to the hand hygiene intervention. The results from trials with a contemporaneous control were conflicting.

Salmonella enterica and Escherichia coli are bacteria of concern to veterinary public health and poultry health. Our research aimed to determine the factors associated with S. enterica and E. coli in commercial broiler chicken barns during the rest period between flocks to identify the best methods of sanitation for bacterial load reduction. This involved collecting samples from September 2015 to July 2016 from the floors of 36 barns before sanitation (baseline) and at 2 time intervals after sanitation, followed by microbiological and molecular analysis. A priori variables of interest included sanitation procedure (dry cleaning, wet cleaning, disinfection), sampling point (baseline, 2 d after sanitation, 6 d after sanitation), and flooring type (concrete, wood). The odds of detecting S. enterica were higher on wooden floors that were wet-cleaned than on concrete floors that were dry-cleaned, lower in the winter and spring than in the fall, and lower when samples were collected 2 d and 6 d after sanitation than at baseline. For E. coli, the concentration was higher on wooden floors than on concrete floors and in the summer than in the fall, and it was lower in postsanitation samples from disinfected barns than in presanitation samples from dry-cleaned barns and in the winter than in the fall. Among E. coli isolates, factors associated with the presence of qacEΔ1, a gene associated with resistance to quaternary ammonium compounds, included sanitation procedure, flooring type, cycle length, and the number of times per yr the barn is disinfected. Our findings highlight the importance of cleaning after litter removal, although the sanitation procedure chosen might differ depending on which pathogen is present and causing disease issues; dry cleaning appears to be preferable for S. enterica control, especially in barns with wooden floors, whereas disinfection appears to be preferable for E. coli reduction.

The impact of antibiotic use for growth promotion in livestock and poultry production on the rise of antimicrobial resistance (AMR) in bacteria led to the ban of this practice in the European Union in 2006 and a restriction of antimicrobial use (AMU) in animal agriculture in Canada and the United States of America. There is a high risk of infectious diseases such as necrotic enteritis due to Clostridium perfringens, and colibacillosis due to avian pathogenic Escherichia coli in antimicrobial-free broiler chickens. Thus, efficient and cost-effective methods for reducing AMU, maintaining good poultry health and reducing public health risks (food safety) are urgently needed for poultry production. Several alternative agents, including plant-derived polyphenolic compounds, have been investigated for their potential to prevent and control diseases through increasing poultry immunity. Many studies in humans reported that plant flavonoids could modulate the immune system by decreasing production of pro-inflammatory cytokines, T-cell activation, and proliferation. Fruits, especially berries, are excellent sources of flavonoids while being rich in nutrients and other functionally important molecules (vitamins and minerals). Thus, fruit byproducts or wastes could be important resources for value-added applications in poultry production. In the context of the circular economy and waste reduction, this review summarizes observed effects of fruit wastes/extracts on the general health and the immunity of poultry.

Background: D/deaf and hard of hearing populations are at higher risk for experiencing physical and mental health problems compared to hearing populations. In addition, they commonly encounter barriers to accessing and benefiting from health services, which largely stem from challenges they face in communicating with healthcare providers. Healthcare providers commonly lack tailored communication skills in caring for D/deaf and hard of hearing populations, which lead to difficulties and dissatisfaction for both staff and D/deaf and hard of hearing communities. This research project aims to develop and evaluate a capacity-building intervention for healthcare providers with the goal of increasing their awareness of D/deaf and hard of hearing individuals' experiences with the healthcare system, their distinct needs, and improving their capacity to communicate effectively with this patient population.Methods: This research project features a participative action research design using qualitative and quantitative methods. Consistent with participative action research, the study will actively involve the target populations, key stakeholders and representative associations. The intervention will be developed and tested through iterative phases. The Integrated Model of Training Evaluation and Effectiveness will guide prospective evaluation of the intervention. The latter will involve qualitative and quantitative assessments in participants before and after the intervention and at 6-months follow-up.Discussion: Results will contribute to research aimed at decreasing barriers to accessing and benefiting from healthcare services for D/deaf and hard of hearing individuals. Findings will be presented to representative associations and political authorities, as well as disseminated at research conferences and in peer-reviewed journals.