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This white paper documents the consensus opinion of the Artificial Intelligence Surgery (AIS) task force on Artificial Intelligence (AI) Ethics and the AIS Editorial Board Study Group on Ethics on the ethical considerations and current trustworthiness of artificial intelligence and autonomous actions in surgery. The ethics were divided into 6 topics defined by the Task Force: Reliability of robotic and AI systems; Respect for privacy and sensitive data; Use of complete and representative (i.e., unbiased) data; Transparencies and uncertainties in AI; Fairness: are we exacerbating inequalities in access to healthcare?; Technology as an equalizer in surgical education. Task Force members were asked to research a topic, draft a section, and come up with several potential consensus statements. These were voted on by members of the Task Force and the Study Group, and all proposals that received > 75 % agreement were adopted and included in the White Paper.

Background Every year since 1982 the BMJ has published a “Christmas issue” as the final issue of the year. Articles in the special issue are lighthearted, sometimes frivolous, but often with serious underlying concerns. There is fierce competition to have a paper published in the Christmas issue. Hypothesis That there is no difference between the numbers of citations, reads and downloads, and Altmetrics scores of papers published in the BMJ’s Christmas issues and the numbers of citations, reads and downloads, and Altmetrics scores of papers published in other issues. Methods We shall search the last issues of the BMJ in each year from 2000 to 2019 inclusive (20 years). We shall use Google Scholar to determine how many citations papers published in each issue have received by July 2022. We shall classify the papers using the terms used in the journal itself and in the Medline entries, where available. We shall initially compare the Christmas issues with the issues that have been published at the end of August in each year studied. Later, we may compare them with issues published at other times of the year. We shall also compare the most cited journal articles at Xmas with the least cited articles, to establish whether careful selection of title or subject might allow citation success and Xmas exposure to be combined. We shall also compare reads and downloads for papers published onwards from 2008, when the BMJ started to count those numbers. Since Altmetrics scores reportedly correlate with citations and readability of articles, we shall also compare Altmetrics scores for papers published onwards from 2014. Inclusion criteria We shall include editorials, papers of various kinds uniformly described in Medline as “journal articles”, and fillers. “Journal articles” generally include research articles of all types (e.g. systematic reviews and meta-analyses, RCTs, and retrospective and prospective observational studies), case reports, historical articles, and nonsystematic review articles. Exclusion criteria We shall exclude book reviews and obituaries and items such as those labelled “Editor’s choice”, “This Week in the BMJ”, “News”, “In brief”, “Short cuts”, and “Minerva”. Analysis We shall calculate medians and interquartile ranges and compare them using nonparametric tests. We shall analyse the complete set of data, the pairs of data in each year (Christmas and August), and subsets of different types of articles (e.g. those labelled “journal articles”).

In the present study, we plan to collect background information about the RDM mistakes of retracted papers by surveying their authors. We will use our RDM taxonomy to categorize the different mistakes and their causes. The results of the proposed study could provide valuable information on what types of these honest mistakes could lead to such a serious consequence as a retraction. We plan to suggest useful tools and practices to prevent these mistakes for those researchers who wish to minimize the risk of a retraction.

Abstract Artificial intelligence developments are essential to the successful deployment of community-wide, MRI-driven prostate cancer diagnosis. AI systems should ensure that the main benefits of biopsy avoidance are delivered while maintaining consistent high specificities, at a range of disease prevalences. Since all current artificial intelligence / computer-aided detection systems for prostate cancer detection are experimental, multiple developmental efforts are still needed to bring the vision to fruition. Initial work needs to focus on developing systems as diagnostic supporting aids so their results can be integrated into the radiologists’ workflow including gland and target outlining tasks for fusion biopsies. Developing AI systems as clinical decision-making tools will require greater efforts. The latter encompass larger multicentric, multivendor datasets where the different needs of patients stratified by diagnostic settings, disease prevalence, patient preference, and clinical setting are considered. AI-based, robust, standard operating procedures will increase the confidence of patients and payers, thus enabling the wider adoption of the MRI-directed approach for prostate cancer diagnosis. Key Points • AI systems need to ensure that the benefits of biopsy avoidance are delivered with consistent high specificities, at a range of disease prevalence. • Initial work has focused on developing systems as diagnostic supporting aids for outlining tasks, so they can be integrated into the radiologists’ workflow to support MRI-directed biopsies. • Decision support tools require a larger body of work including multicentric, multivendor studies where the clinical needs, disease prevalence, patient preferences, and clinical setting are additionally defined.

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This registration contain information about my research article "A novel deep learning method for recognizing texts printed with multiple different printing methods" and its extended/underlying data which are required by publisher (F1000Research).

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Open Science is a movement that aims to share and make scientific knowledge available to society as a whole and to scientific communities around the world, encouraging transparency, rigor, and integrity in all stages of the scientific process, enabling the results to be shared and reused by everyone. Thus, this cross-sectional observational study aims to evaluate the adherence to open science practices of the 100 most cited studies in the dentistry field of the last 10 years, in addition to assessing whether there is any association between the number of citations and adherence to practices of open science.

Open Science is a movement that aims to share and make scientific knowledge available to society as a whole and to scientific communities around the world, encouraging transparency, rigor, and integrity in all stages of the scientific process, enabling the results to be shared and reused by everyone. Thus, this cross-sectional observational study aims to evaluate the adherence to open science practices of the 100 most cited studies in the dentistry field of the last 10 years, in addition to assessing whether there is any association between the number of citations and adherence to practices of open science.

In "Joint EANM/SNMMI/ESTRO Practice Recommendations for the Use of 2-[18F]FDG-PET/CT External Beam Radiation Treatment Planning in Lung Cancer V1.0" clinical indications for PET-CT in (non-)small cell lung cancer are highlighted and selective nodal irradiation is discussed. Additionally, concepts about target definition, target delineation and treatment evaluation are reviewed. (C) 2022 Published by Elsevier B.V.

Aims - To examine eligibility and assessment criteria of research publication recognition awards. - To evaluate potential gender and country biases in the lists of past awardees of the above awards. - To communicate the need for improving awards policies and how this can be done – ultimately making individual publication-related awards more equitable.

Aims - To examine eligibility and assessment criteria of research publication recognition awards. - To evaluate potential gender and country biases in the lists of past awardees of the above awards. - To communicate the need for improving awards policies and how this can be done – ultimately making individual publication-related awards more equitable.

In their fifth meeting at the Vrije Universiteit Amsterdam in 2017 (5th WCRI), the World Conference on Research Integrity (WCRI) adopted the Amsterdam Agenda (AA). The AA is a policy statement stipulating six key elements that researchers doing research on aspects of research integrity preferably should use when preregistering their empirical research projects (https://www.wcrif.org/guidance/amsterdam-agenda). The applicants of this submission form performed an ad hoc study in 2019 using data supplied by paper and poster presenters of the 6th WCRI in Hong Kong, 2019, to find out to which degree researchers had pre-registered the study they were going to present at the 6th WCRI, using either the recommendations of the AA or other recommendations. The first applicant (Sijtsma) presented the results in the final plenary session of 6th WCRI. The pilot study showed that 19% of the 308 presenters had preregistered their research. Of the 56 usable cases, less than half of them provided information on one or more of the six key elements of the AA. Others provided information that invalidated their data, such as an uninformative URL. There was no discernable difference between qualitative and quantitative research. We published our results in the journal Research Integrity and Peer Review (Sijtsma et al., 2021). Our study suffered from two limitations. First, we did no plan our research a priori but used the raw data the 6th WCRI organizers made available on an ad hoc basis. These raw data came from the information 6th WCRI participants provided while registering and submitting their paper and poster proposals. This implied that we had to work with data that were not collected with our study questions in mind. Second, given highly restrictive time limits, the WCRI organizers were unable to receive participants’ consent for using their data once we planned our research, and we were unable to receive timely consent of an ethics committee and to preregister our research. The present proposal continues the 2019 research, but improves both its content and fully obeys procedural requirements. That is, we plan the data collection a priori, ask participants for their consent to use their anonymized data, request consent by an ethics committee, and pre-register the study. Sijtsma, K., Emons, W. H. M., Steneck, N. H., & Bouter, L. M. (2021). Steps toward preregistration of research on research integrity. Research Integrity and Peer Review, 6. https://doi.org/10.1186/s41073-021-00108-4

Description: This serves as a pre-registration for the study of executive functioning assessment in virtual reality. Draft summary Virtual reality immerses the individual in a computerised situation in which they can move coherently in space and interact with objects in the virtual environment. Virtual reality is an interesting technology for cognitive assessment because it is more embodied than traditional paper-and-pencil testing situations. Virtual reality is more respectful of the conception of function-based neuropsychology, as opposed to construct-based neuropsychology. Virtual reality also facilitates the tracking of kinematic information on the one hand and the temporal tracking of activities on the other, which can add to the quality of the assessment. This study aims to present three virtual reality environments dedicated to the evaluation of cognitive functions. It also aims to evaluate the relationship between standard paper/pencil and tablet assessments and virtual reality assessments. Based on the results, the discussion will focus on the advantages (or disadvantages) of kinematic tracking and embodied, situated and spatialized tests for cognitive assessment.

MicroRNAs are small (approximately 22 nucleotides), endogenous, noncoding, highly stable, and gene-regulating RNAs. Their dysregulation were linked to many diseases, such as diabetes and cancers. Since the first microRNA was found in 1993, a lot of microRNAs with countless papers were discoveried. At the same time, many papers on microRNA research were retracted, which had a bad impact on evidence-based research and clinical decision-making. This study aims to analysis the trends and characteristics of retracted papers on microRNA study to facilitate good research and better science.

Background Brucellosis, as a serious zoonotic infectious disease, has been recognized as a re-emerging disease in the developing countries worldwide. In china, the incidence of brucellosis is increasing each year, seriously threatening the health of humans as well as animal populations. Despite a quite number of diagnostic methods currently being used for brucellosis, innovative technologies are still needed for its rapid and accurate diagnosis, especially in area where traditional diagnostic is unavailable. Methodology/Principal findings In this study, a total of 22 B cell linear epitopes were predicted from five Brucella outer membrane proteins (OMPs) using an immunoinformatic approach. These epitopes were then chemically synthesized, and with the method of indirect ELISA (iELISA), each of them displayed a certain degree of capability in identifying human brucellosis positive sera. Subsequently, a fusion protein consisting of the 22 predicted epitopes was prokaryotically expressed and used as diagnostic antigen in a newly established brucellosis testing method, nano-ZnO modified paper-based ELISA (nano-p-ELISA). According to the verifying test using a collection of sera collected from brucellosis and non-brucellosis patients, the sensitivity and specificity of multiepitope based nano-p-ELISA were 92.38% and 98.35% respectively. The positive predictive value was 98.26% and the negative predictive value was 91.67%. The multiepitope based fusion protein also displayed significantly higher specificity than Brucella lipopolysaccharide (LPS) antigen. Conclusions B cell epitopes are important candidates for serologically testing brucellosis. Multiepitope fusion protein based nano-p-ELISA displayed significantly sensitivity and specificity compared to Brucella LPS antigen. The strategy applied in this study will be helpful to develop rapid and accurate diagnostic method for brucellosis in human as well as animal populations., Author summary Brucellosis is one of the most important zoonosis in the world and has caused tremendous economic losses in agriculture and animal husbandry in many countries. Developing rapid, sensitive and specific diagnostic methods is very important for early detection and treatment of brucellosis patients. In this study, a novel diagnostic technique, nano-ZnO modified paper ELISA, was established. The antigen used in this technique was a fusion protein containing multiple B cell epitopes, which were predicted from Brucella major outer membrane proteins such as Bp26, Omp31, Omp16, Omp2b and Omp25. Comparing to traditional LPS antigen, this multiepitope based antigen displayed considerably higher sensitivity and higher specificity in laboratory. With the strategy described in this paper, more efficient epitopes and protein antigen can be identified in the future. Currently, LPS antigen is only prepared from live Brucella, while protein antigen can be produced in large quantities in prokaryotic expression system. In addition to nano-p-ELISA, this protein antigen can also be used for development other methods such as fluorescent polarization assay (FPA) and immunochromatographic assay (ICA) to meet the varied demand for brucellosis testing.

The advantages of administering questionnaires online include savings of time, savings of money, avoidance of data entry errors (Pasveer & Ellard, 1998) and less missing data (Stanton, 1998; Wood et al., 2006). In addition, participants are provided with the flexibility to complete the questionnaires whenever it fits into their schedule. In 2005, almost two decades ago, a still ongoing cross-sectional observational study on psychosocial aspects and psychological stress of cancer outpatients was launched at the Medical University of Vienna, including two standardised questionnaires, namely the Hospital Anxiety and Depression Scale (HADS; Zigmond & Snaith, 1983) and the Posttraumatic Symptom Scale (PTSS-10; Maercker, 2003; Stoll et al. 1999). Administration mode of this study will be switched from paper-pencil to online assessment. For boths questionnaires, we aim to investigate whether measurement equivalence between administration modes can be assumed.

COVID-19 has accelerated a virtual era of consultations, which adds difficulties when assessing pain. Pen-to-paper pain diagrams, a well-used method will be replaced by electronic pain diagrams, a newer technology. This scoping review aims to assess the usability of pain diagrams, give recommendations on use and develop a gap map to allow routes for future research to ensure pain diagrams are effective, leading to more consistent use in virtual healthcare.

The aim of this review is firstly to identify patient-reported outcome measures administered to children and youth up to and including the age of 24 years to assess for outcomes related to their physical health condition, mental health status, overall wellbeing, thoughts, feelings, and personal experiences. Secondly, the review aims to critically appraise and compare the measurement equivalence between electronic/digital/telephone-administered and paper-based patient-reported outcome measures administered to children and youth.

Scientific publications may be retracted for different reasons, including misconduct. Empirical data suggest an increasing rate of retractions within the biomedical literature. To our knowledge, a comprehensive assessment of retractions of biomedical papers from authors affiliated with a scientific institution in Germany has not yet been performed.

This page contains the document for the pre-registration of the paper with the preliminary title "Familial resemblance in psychosocial vulnerability: A study of patients with depressive and anxiety disorders and their siblings".

This is a frozen copy of a pre-registered project containing the data for following publication: Hoorelbeke, K., Van den Bergh, N., De Raedt, R., Wichers, M., & Koster, E.H.W. (2021). Preventing recurrence of depression: Long-term effects of a randomized controlled trial on cognitive control training for remitted depressed patients. Clinical Psychological Science.

A systematic review of publications from 7 databases on the hypothesis of chemical imbalances causing mental distress ("the chemical imbalance theory")

Personalised Nutrition for Older Adults: Design Challenges, SME barriers, and Options and Competencies for Innovation

Scoping review

Data supporting the peer-reviewed manuscript: Defining and validating regenerative farm systems using a composite of ranked agricultural practices Tommy Fenster Claire E. LaCanne Jacob R. Pecenka Ryan B. Schmid Michael M. Bredeson Katya Busenitz Alex Michels Kelton D. Welch Jonathan G. Lundgren

Although regression models play a central role in the analysis of medical research projects, there still exist many misconceptions on various aspects of modeling leading to faulty analyses. Indeed, the rapidly developing statistical methodology and its recent advances in regression modeling do not seem to be adequately reflected in many medical publications. This problem of knowledge transfer from statistical research to application was identified by some medical journals, which have published series of statistical tutorials and (shorter) papers mainly addressing medical researchers. The aim of this review was to assess the current level of knowledge with regard to regression modeling contained in such statistical papers. We searched for target series by a request to international statistical experts. We identified 23 series including 57 topic-relevant articles. Within each article, two independent raters analyzed the content by investigating 44 predefined aspects on regression modeling. We assessed to what extent the aspects were explained and if examples, software advices, and recommendations for or against specific methods were given. Most series (21/23) included at least one article on multivariable regression. Logistic regression was the most frequently described regression type (19/23), followed by linear regression (18/23), Cox regression and survival models (12/23) and Poisson regression (3/23). Most general aspects on regression modeling, e.g. model assumptions, reporting and interpretation of regression results, were covered. We did not find many misconceptions or misleading recommendations, but we identified relevant gaps, in particular with respect to addressing nonlinear effects of continuous predictors, model specification and variable selection. Specific recommendations on software were rarely given. Statistical guidance should be developed for nonlinear effects, model specification and variable selection to better support medical researchers who perform or interpret regression analyses.

Recognizing the increase in cancer incidence globally and the need for effective cancer control interventions, several organizations, professional bodies, and international institutions have proposed strategies to improve treatment options and reduce mortality along with minimizing overall incidence. Despite these efforts, an estimated 9.6 million deaths in 2018 was attributed to this noncommunicable disease, making it the second leading cause of death worldwide. Left unchecked, this will further increase in scale, with an estimated 29.5 million new cases and 16.3 million deaths occurring worldwide in 2040. Although it is known and generally accepted that cancer services must include radiotherapy, such access is still very limited in many parts of the world, especially in low- and middle-income countries. After thorough review of the current status of radiotherapy including programs worldwide, as well as achievements and challenges at the global level, the International Atomic Energy Agency convened an international group of experts representing various radiation oncology societies to take a closer look into the current status of radiotherapy and provide a road map for future directions in this field. It was concluded that the plethora of global and regional initiatives would benefit further from the existence of a central framework, including an easily accessible repository through which better coordination can be done. Supporting this framework, a practical inventory of competencies needs to be made available on a global level emphasizing the knowledge, skills, and behavior required for a safe, sustainable, and professional practice for various settings. This white paper presents the current status of global radiotherapy and future directions for the community. It forms the basis for an action plan to be developed with professional societies worldwide.

Summary The IOF Epidemiology and Quality of Life Working Group has reviewed the potential role of population screening for high hip fracture risk against well-established criteria. The report concludes that such an approach should strongly be considered in many health care systems to reduce the burden of hip fractures. Introduction The burden of long-term osteoporosis management falls on primary care in most healthcare systems. However, a wide and stable treatment gap exists in many such settings; most of which appears to be secondary to a lack of awareness of fracture risk. Screening is a public health measure for the purpose of identifying individuals who are likely to benefit from further investigations and/or treatment to reduce the risk of a disease or its complications. The purpose of this report was to review the evidence for a potential screening programme to identify postmenopausal women at increased risk of hip fracture. Methods The approach took well-established criteria for the development of a screening program, adapted by the UK National Screening Committee, and sought the opinion of 20 members of the International Osteoporosis Foundation’s Working Group on Epidemiology and Quality of Life as to whether each criterion was met (yes, partial or no). For each criterion, the evidence base was then reviewed and summarized. Results and Conclusion The report concludes that evidence supports the proposal that screening for high fracture risk in primary care should strongly be considered for incorporation into many health care systems to reduce the burden of fractures, particularly hip fractures. The key remaining hurdles to overcome are engagement with primary care healthcare professionals, and the implementation of systems that facilitate and maintain the screening program.

ispartof: ASIA-PACIFIC JOURNAL OF OPHTHALMOLOGY vol:11 issue:1 pages:89-90 ispartof: location:China status: published

Non-invasive diagnosis on biological liquid samples, such as urine, sweat, saliva, and tears, may allow patients to evaluate their health by themselves. To obtain accurate diagnostic results, target liquid must be precisely sampled. Conventionally, urine sampling using filter paper can be given as an example sampling, but differences in the paper structure can cause variations in sampling volume. This paper describes precise liquid sampling using synthetic microfluidic papers, which are composed of obliquely combined micropillars. Sampling volume accuracy was investigated using different designs and collection methods to determine the optimal design and sample collecting method. The optimized protocol was followed to accurately measure potassium concentration using synthetic microfluidic paper and a commercially available densitometer, which verified the usefulness of the synthetic microfluidic papers for precision sampling.

Inter-professional education (IPE) can support professionals in developing their ability to work collaboratively. This position paper from the European Forum for Primary Care considers the design and implementation of IPE within primary care. This paper is based on workshops and is an evidence review of good practice. Enablers of IPE programmes are involving patients in the design and delivery, providing a holistic focus, focussing on practical actions, deploying multi-modal learning formats and activities, including more than two professions, evaluating formative and summative aspects, and encouraging team-based working. Guidance for the successful implementation of IPE is set out with examples from qualifying and continuing professional development programmes.

Contains fulltext : 225338.pdf (Publisher’s version ) (Open Access) OBJECTIVES: The number of older people dying in long-term care facilities (LTCFs) is increasing globally, but care quality may be variable. A framework was developed drawing on empirical research findings from the Palliative Care for Older People (PACE) study and a scoping review of literature on the implementation of palliative care interventions in LTCFs. The PACE study mapped palliative care in LTCFs in Europe, evaluated quality of end-of-life care and quality of dying in a cross-sectional study of deceased residents of LTCFs in 6 countries, and undertook a cluster-randomized control trial that evaluated the impact of the PACE Steps to Success intervention in 7 countries. Working with the European Association for Palliative Care, a white paper was written that outlined recommendations for the implementation of interventions to improve palliative and end-of-life care for all older adults with serious illness, regardless of diagnosis, living in LTCFs. The goal of the article is to present these key domains and recommendations. DESIGN: Transparent expert consultation. SETTING: International experts in LTCFs. PARTICIPANTS: Eighteen (of 20 invited) international experts from 15 countries participated in a 1-day face-to-face Transparent Expert Consultation (TEC) workshop in Bern, Switzerland, and 21 (of 28 invited) completed a follow-up online survey. METHODS: The TEC study used (1) a face-to-face workshop to discuss a scoping review and initial recommendations and (2) an online survey. RESULTS: Thirty recommendations about implementing palliative care for older people in LTCFs were refined during the TEC workshop and, of these, 20 were selected following the survey. These 20 recommendations cover domains at micro (within organizations), meso (across organizations), and macro (at national or regional) levels addressed in 3 phases: establishing conditions for action, embedding in everyday practice, and sustaining ongoing change. CONCLUSIONS AND IMPLICATIONS: We developed a framework of 20 recommendations to guide implementation of improvements in palliative care in LTCFs.

Rabies is a lethal zoonotic encephalomyelitis that causes an estimated 59,000 human deaths yearly worldwide. Although developing countries of Asia and Africa bear the heaviest burden, surveillance and disease detection in these countries is often hampered by the absence of local laboratories able to diagnose rabies and/or the difficulties of sample shipment from low-access areas to national reference laboratories. Filter papers offer a convenient cost-effective alternative for the sampling, shipment, and storage of biological materials for the diagnosis of many pathogens including rabies virus, yet the properties of diagnostic tests using this support have not been evaluated thoroughly. Sensitivity and specificity of molecular diagnosis of rabies infection using a reverse transcription followed by a hemi-nested polymerase chain reaction (RT-hn-PCR) either directly on brain tissue or using brain tissue dried on filter paper were assessed on 113 suspected field animal samples in comparison to the direct fluorescent antibody test (FAT) recommended by the World Health Organization as one of the reference tests for rabies diagnosis. Impact of the duration of the storage was also evaluated. The sensitivity and the specificity of RT-hn-PCR i) on brain tissue were 96.6% (95% CI: [88.1–99.6]) and 92.7% (95% CI: [82.4–98.0]) respectively and ii) on brain tissue dried on filter paper 100% (95% CI: [93.8–100.0]) and 90.9% (95% CI: [80.0–97.0]) respectively. No loss of sensitivity of RT-hn-PCR on samples of brain tissue dried on filter paper left 7 days at ambient temperature was detected indicating that this method would enable analyzing impregnated filter papers sent to the national reference laboratory at ambient temperature within a 1-week shipment time. It could therefore be an effective alternative to facilitate storage and shipment of samples from low-access areas to enhance and expand rabies surveillance., Author summary Dogs are responsible for 99% of human rabies deaths. Facilitating diagnostic of rabid dogs can help further identify i) people who were exposed to rabies in order to encourage them to seek post exposure prophylaxis and ii) other exposed animals to break the transmission chain (i.e. prevent them from further transmitting the virus to other people and animals). Yet, the reference diagnostic method for animal rabies requires brain samples to be collected post-mortem and shipped under temperature-controlled conditions. The shipping of such samples is complex in low-access areas, especially in low income countries, which are often those that bear the heaviest rabies burden. Filter papers offer a convenient alternative for biological sample shipment and storage. Here the efficiency of a molecular diagnostic method applied to brain tissue dried on filter paper is compared to one of the reference methods, the direct fluorescent antibody test. Our results show it has an excellent sensitivity (it does not miss any positive samples), even when filter papers are left 7 days at ambient temperature. These results let us foresee a cost-effective alternative facilitating shipment, storage and testing of samples from rabies suspected animals from low-access areas. This could considerably enhance and expand rabies surveillance in low-income countries, allowing a more comprehensive evaluation of rabies burden, and thus reinforcing arguments for allocating funds to rabies control policies.

BACKGROUND: The partograph has been endorsed by World Health Organization (WHO) since 1994 which presents an algorithm for assessing maternal and foetal conditions and labor progression. Monitoring labour with a partograph can reduce adverse pregnancy outcomes such as prolonged labor, emergency C-sections, birth asphyxia and stillbirths. However, partograph use is still very low, particularly in low and middle income countries (LMICs). In Bangladesh the reported partograph user rate varies from 1.4% to 33.0%. Recently, an electronic version of the partograph, with the provision of online data entry and user aid for emergency clinical support, has been tested successfully in different settings. With this proven evidence, we conducted and operations research to test the feasibility and effectiveness of implementing an e-partograph, for the first time, in 2 public hospitals in Bangladesh.METHODS: We followed a prospective crossover design. Two secondary level referral hospitals, Jessore and Kushtia District Hospital (DH) were the study sites. All pregnant women who delivered in the study hospitals were the study participants. All nurse-midwives working in the labor ward of study hospitals were trained on appropriate use of both types of partograph along with standard labour management guidelines. Collected quantitative data was analyzed using SPSS 23 statistical software. Discrete variables were expressed as percentages and presented as frequency distribution and cross tabulations. Chi square tests were employed to test the association between exposure and outcome variables. Potential confounding factors were adjusted using multivariate binary logistic regression methods. Ethical approval was obtained from the institutional review board of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b).FINDINGS: In total 2918 deliveries were conducted at Jessore DH and 2312 at Kushtia DH during one-year study period. Of them, 1012 (506 in each facility) deliveries were monitored using partograph (paper or electronic). The trends of facility based C-section rates was downwards in both the hospitals; 43% to 37% in Jessore and from 36% to 25% in Kushtia Hospital. There was a significant reduction of prolonged labour with e-partograph use. In Kushtia DH, the prolonged labour rate was 42% during phase 1 with the paper version which came down to 29% during phase-2 with the e-partograph use. The similar result was observed in Jessore DH where the prolonged labour rate reduced to 7% with paper partograph from the reported 30% prolonged labour with e-partograph. The e-partograph user rate was higher than the paper partograph during both phases (phase 1: 3.31, CI: 2.04-5.38, p < .001 and in phase 2: 15.20 CI: 6.36-36.33, p < .001) after adjusting for maternal age, parity, gestational age, religion, mother's education, husband's education, and fetal sex.CONCLUSION: The partograph user rate has significantly improved with the e- partograph and was associated with an overall reduction in cesarean births. Use of the e-partograph was also associated with reduced rates of prolonged labour. This study has added to the growing body of evidence on the positive impact of e-partograph use. We recommend implementing e-partograph intervention at scale in both public and private hospitals in Bangladesh.TRIAL REGISTRATION: ClinicalTrials.gov NCT03509103.

Social interactions have large effects on individual physiology and fitness. In the immediate sense, social stimuli are often highly salient and engaging. Over longer time scales, competitive interactions often lead to distinct social ranks and differences in physiology and behavior. Understanding how initial responses lead to longer-term effects of social interactions requires examining the changes in responses over time. Here we examined the effects of social interactions on transcriptomic signatures at two times, at the end of a 45-minute interaction and 4 hours later, in female Polistes fuscatus paper wasp foundresses. Female P. fuscatus have variable facial patterns that are used for visual individual recognition, so we separately examined the transcriptional dynamics in the optic lobe and the non-visual brain. Results demonstrate much stronger transcriptional responses to social interactions in the non-visual brain compared to the optic lobe. Differentially regulated genes in response to social interactions are enriched for memory-related transcripts. Comparisons between winners and losers of the encounters revealed similar overall transcriptional profiles at the end of an interaction, which significantly diverged over the course of 4 hours, with losers showing changes in expression levels of genes associated with aggression and reproduction in paper wasps. On nests, subordinate foundresses are less aggressive, do more foraging and lay fewer eggs compared to dominant foundresses and we find losers shift expression of many genes in the non-visual brain, including vitellogenin, related to aggression, worker behavior, and reproduction within hours of losing an encounter. These results highlight the early neurogenomic changes that likely contribute to behavioral and physiological effects of social status changes in a social insect., Author summary Aggressive interactions often create inequalities–some individuals win while others lose. Winning versus losing can lead to large physiological differences between individuals, including different neurogenomic profiles between winners and losers. How this information about contest outcome leads to distinct neurogenomic profiles is poorly understood. Here we examine gene expression in response to aggressive social encounters in paper wasps, which naturally form dominance hierarchies on their nests in the wild. Shortly following encounters winners and losers have similar expression profiles, likely because similar mechanisms are engaged by social experiences. Four hours later, we find divergent neurogenomic profiles between winners and losers, with losers showing larger shifts in expression compared to winners. Many of the most dynamically expressed genes have been previously associated with dominance and caste differences in paper wasps showing how a single interaction can engage many of the same genomic networks that are involved in mediating more dramatic differences in queen-worker behavioral differences are also involved in responses shortly following social interactions.

Various data sharing platforms are being developed to enhance the sharing of cohort data by addressing the fragmented state of data storage and access systems. However, policy challenges in several domains remain unresolved. The euCanSHare workshop was organized to identify and discuss these challenges and to set the future research agenda. Concerns over the multiplicity and long-term sustainability of platforms, lack of resources, access of commercial parties to medical data, credit and recognition mechanisms in academia and the organization of data access committees are outlined. Within these areas, solutions need to be devised to ensure an optimal functioning of platforms.

Background Global estimates for cholera annually approximate 4 million cases worldwide with 95,000 deaths. Recent outbreaks, including Haiti and Yemen, are reminders that cholera is still a global health concern. Cholera outbreaks can rapidly induce high death tolls by overwhelming the capacity of health facilities, especially in remote areas or areas of civil unrest. Recent studies demonstrated that stool specimens preserved on filter paper facilitate molecular analysis of Vibrio cholerae in resource limited settings. Specimens preserved in a rapid, low-cost, safe and sustainable manner for sequencing provides previously unavailable data about circulating cholera strains. This may ultimately contribute new information to shape public policy response on cholera control and elimination. Methodology/Principal findings Whole genome sequencing (WGS) recovered close to a complete sequence of the V. cholerae O1 genome with satisfactory genome coverage from stool specimens enriched in alkaline peptone water (APW) and V. cholerae culture isolates, both spotted on filter paper. The minimum concentration of V. cholerae DNA sufficient to produce quality genomic information was 0.02 ng/μL. The genomic data confirmed the presence or absence of genes of epidemiological interest, including cholera toxin and pilus loci. WGS identified a variety of diarrheal pathogens from APW-enriched specimen spotted filter paper, highlighting the potential for this technique to explore the gut microbiome, potentially identifying co-infections, which may impact the severity of disease. WGS demonstrated that these specimens fit within the current global cholera phylogenetic tree, identifying the strains as the 7th pandemic El Tor. Conclusions WGS results allowed for mapping of short reads from APW-enriched specimen and culture isolate spotted filter papers. This provided valuable molecular epidemiological sequence information on V. cholerae strains from remote, low-resource settings. These results identified the presence of co-infecting pathogens while providing rare insight into the specific V. cholerae strains causing outbreaks in cholera-endemic areas., Author summary Cholera affects more than 4 million people globally every year; people predominantly living in poverty or in resource-constrained conditions including political crises or natural disasters. Cholera’s typical presentation is characterized by rapid onset of acute watery diarrhea and vomiting which can progress from watery stool to shock in as little as four hours. Laboratory conditions needed for culture confirmation and strain preservation are rarely to never present in these affected areas. In fact, many cholera endemic areas in Sub-Saharan African are so remote that even treatment response alone is often challenging. Here we present the genomic analysis of DNA extracted from dried filter paper, which is a low-cost, low-tech and sustainable method. Previously this method has facilitated cholera confirmation by PCR, but we demonstrate that this method is also suitable for whole genome sequencing and subsequent strain characterization by presenting the analysis of samples from an outbreak in a remote area of Cameroon. This method will facilitate the understanding of the molecular epidemiology in cholera-prone areas, which were previously too challenging to attempt. It also introduces a method that can be used on a broader scale for diarrheal disease surveillance, including providing a window into co-infection and microbiome analyses.

The breakthrough potentials of research papers can be explained by their boundary-spanning qualities. Here, for the first time, we apply the structural variation analysis (SVA) model and its affiliated metrics to investigate the extent to which such qualities characterize a group of Nobel Prize winning papers. We find that these papers share remarkable boundary-spanning traits, marked by exceptional abilities to connect disparate and topically-diverse clusters of research papers. Further, their publications exert structural variations on the scale that significantly alters the betweenness centrality distributions of existing intellectual space. Overall, SVA not only provides a set of leading indicators for describing future Nobel Prize winning papers, but also broadens our understanding of the similar prize-winning properties that may have been overlooked among other regular publications., 27 pages, 8 figures, 9 tables. Submitted to Frontiers in Research Metrics and Analytics

ObjectiveTo evaluate the consistency of causal statements in observational studies published in The BMJ.DesignReview of observational studies published in a general medical journal.Data sourceCohort and other longitudinal studies describing an exposure-outcome relationship published in The BMJ in 2018. We also had access to the submitted papers and reviewer reports.Main outcome measuresProportion of published research papers with ‘inconsistent’ use of causal language. Papers where language was consistently causal or non-causal were classified as ‘consistently causal’ or ‘consistently not causal’, respectively. For the ‘inconsistent’ papers, we then compared the published and submitted version.ResultsOf 151 published research papers, 60 described eligible studies. Of these 60, we classified the causal language used as ‘consistently causal’ (48%), ‘inconsistent’ (20%) and ‘consistently not causal’(32%). Eleven out of 12 (92%) of the ‘inconsistent’ papers were already inconsistent on submission. The inconsistencies found in both submitted and published versions were mainly due to mismatches between objectives and conclusions. One section might be carefully phrased in terms of association while the other presented causal language. When identifying only an association, some authors jumped to recommending acting on the findings as if motivated by the evidence presented.ConclusionFurther guidance is necessary for authors on what constitutes a causal statement and how to justify or discuss assumptions involved. Based on screening these papers, we provide a list of expressions beyond the obvious ‘cause’ word which may inspire a useful more comprehensive compendium on causal language.

Paracrine and endocrine roles have increasingly been ascribed to extracellular vesicles (EVs) generated by multicellular organisms. Central to the biogenesis, content, and function of EVs are their delimiting lipid bilayer membranes. To evaluate research progress on membranes and EVs, the International Society for Extracellular Vesicles (ISEV) conducted a workshop in March 2018 in Baltimore, Maryland, USA, bringing together key opinion leaders and hands-on researchers who were selected on the basis of submitted applications. The workshop was accompanied by two scientific surveys and covered four broad topics: EV biogenesis and release; EV uptake and fusion; technologies and strategies used to study EV membranes; and EV transfer and functional assays. In this ISEV position paper, we synthesize the results of the workshop and the related surveys to outline important outstanding questions about EV membranes and describe areas of consensus. The workshop discussions and survey responses reveal that while much progress has been made in the field, there are still several concepts that divide opinion. Good consensus exists in some areas, including particular aspects of EV biogenesis, uptake and downstream signalling. Areas with little to no consensus include EV storage and stability, as well as whether and how EVs fuse with target cells. Further research is needed in these key areas, as a better understanding of membrane biology will contribute substantially towards advancing the field of extracellular vesicles. Fil: Russell, Ashley E.. University Johns Hopkins; Estados Unidos Fil: Sneider, Alexandra. University Johns Hopkins; Estados Unidos Fil: Witwer, Kenneth W.. University Johns Hopkins; Estados Unidos Fil: Bergese, Paolo. Università Degli Studi Di Brescia; Italia Fil: Bhattacharyya, Suvendra N.. Indian Institute of Chemical Biology; India Fil: Cocks, Alexander. Cardiff University; Reino Unido Fil: Cocucci, Emanuele. Ohio State University; Estados Unidos Fil: Erdbrügger, Uta. University of Virginia; Estados Unidos Fil: Falcon Perez, Juan M.. Ikerbasque Basque Foundation for Science; España Fil: Freeman, David W.. National Institute On Aging National Institute for Helth ; Estados Unidos Fil: Gallagher, Thomas M.. Loyola University Of Chicago; Estados Unidos Fil: Hu, Shuaishuai. Technological University Dublin; Irlanda Fil: Huang, Yiyao. University Johns Hopkins; Estados Unidos. Southern Medical University; China Fil: Jay, Steven M.. University of Maryland; Estados Unidos Fil: Kano, Shin-ichi. The University of Alabama at Birmingham School of Medicine; Estados Unidos Fil: Lavieu, Gregory. Institut Curie; Francia Fil: Leszczynska, Aleksandra. University of California at San Diego; Estados Unidos Fil: Llorente, Alicia M.. Oslo University Hospital; Noruega Fil: Lu, Quan. Harvard University. Harvard School of Public Health; Estados Unidos Fil: Mahairaki, Vasiliki. University Johns Hopkins; Estados Unidos Fil: Muth, Dillon C.. University Johns Hopkins; Estados Unidos Fil: Noren Hooten, Nicole. National Institute On Aging National Institute for Helth ; Estados Unidos Fil: Ostrowski, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Prada, Ilaria. Consiglio Nazionale delle Ricerche; Italia Fil: Sahoo, Susmita. Icahn School of Medicine at Mount Sinai ; Estados Unidos Fil: Schøyen, Tine Hiorth. Uit The Arctic University Of Norway; Noruega. University Johns Hopkins; Estados Unidos Fil: Sheng, Lifuy. University of Washington. School of Medicine; Estados Unidos Fil: Tesch, Deanna. Shaw University; Estados Unidos Fil: Van Niel, Guillaume. No especifíca; Fil: Vandenbroucke, Roosmarijn E.. University of Ghent; Bélgica Fil: Verweij, Frederik J.. No especifíca; Fil: Villar, Ana V.. Universidad de Cantabria; España Fil: Wauben, Marca. University of Utrecht; Países Bajos Fil: Wehman, Ann M.. Universität Würzburg; Alemania Fil: Ardavan, Arzhang. Peking University; ; China Fil: Carter, David Raul Francisco. Oxford Brookes University; Reino Unido Fil: Vader, Pieter. University Medical Center Utrecht; Países Bajos

Microbial fuel cells (MFCs) can evolve in a viable technology if environmentally sound materials are developed and became available at low cost for these devices. This is especially important not only for the designing of large wastewater treatment systems, but also for the fabrication of low-cost, single-use devices. In this work we synthesized membranes by a simple procedure involving easily-biodegradable and economic materials such as poly (vinyl alcohol) (PVA), chitosan (CS) and the composite PVA:CS. Membranes were chemical and physically characterized and compared to Nafion®. Performance was studied using the membrane as separator in a typical H-Type MFCs showing that PVA:CS membrane outperform Nafion® 4 times (power production) while being 75 times more economic. We found that performance in MFC depends over interactions among several membrane characteristics such as oxygen permeability and ion conductivity. Moreover, we design a paper-based micro-scale MFC, which was used as a toxicity assay using 16 µL samples containing formaldehyde as a model toxicant. The PVA:CS membrane presented here can offer low environmental impact and become a very interesting option for point of need single-use analytical devices, especially in low-income countries where burning is used as disposal method, and toxic fluoride fumes (from Nafion®) can be released to the environment. Fil: Gonzalez Pabon, Maria Jesus. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Figueredo, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Martínez Casillas, Diana Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Corton, Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina

International audience; The differential diagnosis of differences or disorders of sex development (DSD) belongs to the most complex fields in medicine. It requires a multidisciplinary team conducting a synoptic and complementary approach consisting of thorough clinical, hormonal and genetic workups. This position paper of EU COST (European Cooperation in Science and Technology) Action BM1303 'DSDnet' was written by leading experts in the field and focuses on current best practice in genetic diagnosis in DSD patients. Ascertainment of the karyotpye defines one of the three major diagnostic DSD subclasses and is therefore the mandatory initial step. Subsequently, further analyses comprise molecular studies of monogenic DSD causes or analysis of copy number variations (CNV) or both. Panels of candidate genes provide rapid and reliable results. Whole exome and genome sequencing (WES and WGS) represent valuable methodological developments that are currently in the transition from basic science to clinical routine service in the field of DSD. However, in addition to covering known DSD candidate genes, WES and WGS help to identify novel genetic causes for DSD. Diagnostic interpretation must be performed with utmost caution and needs careful scientific validation in each DSD case.

ObjectivesRecently, the results of two economic evaluations were published both of which seemingly demonstrate the cost-effectiveness of sofosbuvir-based regimens for the treatment of chronic hepatitis C genotype 1 infection in Germany. Both analyses were sponsored by the manufacturer of sofosbuvir and use a different methodology: Whereas one evaluation is based on a conventional cost-utility analysis, the other rests upon the efficiency-frontier method used by the German Institute for Quality and Efficiency in Health Care (IQWiG). The purpose of this study is to reanalysis the results of both economic evaluations in combination.DesignReanalysis of published decision modelling results.SettingPrimary care in Germany.ParticipantsPatients with chronic hepatitis C genotype 1 infection (treatment-naïve and -experienced, cirrhotic and non-cirrhotic).InterventionsSofosbuvir, other anti-hepatitis C virus drugs, and no treatment.Primary and secondary outcome measuresCost per unit of health benefit and cost per quality-adjusted life year.ResultsReanalysis of the results of both economic evaluations in combination reveals an unclear rationale for choosing the selected cost-effectiveness methods as well as a potential publication bias, favoring the product of the manufacturer. Based on the reanalysis, sofosbuvir is not cost-effective in treatment-experienced non-cirrhotic patients, potentially lacks cost-effectiveness in treatment-experienced cirrhotic patients, and is only partially cost-effective in treatment-naïve non-cirrhotic patients. Taken together, these results indicate a lack of cost-effectiveness in three quarters of the German patient population.ConclusionsTwo economic evaluations on sofosbuvir suggest, in combination, that sofosbuvir cannot be considered a cost-effective treatment in three quarters of the German patient population.

Background Digitally enabled rehabilitation may lead to better outcomes but has not been tested in large pragmatic trials. We aimed to evaluate a tailored prescription of affordable digital devices in addition to usual care for people with mobility limitations admitted to aged care and neurological rehabilitation. Methods and findings We conducted a pragmatic, outcome-assessor-blinded, parallel-group randomised trial in 3 Australian hospitals in Sydney and Adelaide recruiting adults 18 to 101 years old with mobility limitations undertaking aged care and neurological inpatient rehabilitation. Both the intervention and control groups received usual multidisciplinary inpatient and post-hospital rehabilitation care as determined by the treating rehabilitation clinicians. In addition to usual care, the intervention group used devices to target mobility and physical activity problems, individually prescribed by a physiotherapist according to an intervention protocol, including virtual reality video games, activity monitors, and handheld computer devices for 6 months in hospital and at home. Co-primary outcomes were mobility (performance-based Short Physical Performance Battery [SPPB]; continuous version; range 0 to 3; higher score indicates better mobility) and upright time as a proxy measure of physical activity (proportion of the day upright measured with activPAL) at 6 months. The dataset was analysed using intention-to-treat principles. The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12614000936628). Between 22 September 2014 and 10 November 2016, 300 patients (mean age 74 years, SD 14; 50% female; 54% neurological condition causing activity limitation) were randomly assigned to intervention (n = 149) or control (n = 151) using a secure online database (REDCap) to achieve allocation concealment. Six-month assessments were completed by 258 participants (129 intervention, 129 control). Intervention participants received on average 12 (SD 11) supervised inpatient sessions using 4 (SD 1) different devices and 15 (SD 5) physiotherapy contacts supporting device use after hospital discharge. Changes in mobility scores were higher in the intervention group compared to the control group from baseline (SPPB [continuous, 0–3] mean [SD]: intervention group, 1.5 [0.7]; control group, 1.5 [0.8]) to 6 months (SPPB [continuous, 0–3] mean [SD]: intervention group, 2.3 [0.6]; control group, 2.1 [0.8]; mean between-group difference 0.2 points, 95% CI 0.1 to 0.3; p = 0.006). However, there was no evidence of a difference between groups for upright time at 6 months (mean [SD] proportion of the day spent upright at 6 months: intervention group, 18.2 [9.8]; control group, 18.4 [10.2]; mean between-group difference −0.2, 95% CI −2.7 to 2.3; p = 0.87). Scores were higher in the intervention group compared to the control group across most secondary mobility outcomes, but there was no evidence of a difference between groups for most other secondary outcomes including self-reported balance confidence and quality of life. No adverse events were reported in the intervention group. Thirteen participants died while in the trial (intervention group: 9; control group: 4) due to unrelated causes, and there was no evidence of a difference between groups in fall rates (unadjusted incidence rate ratio 1.19, 95% CI 0.78 to 1.83; p = 0.43). Study limitations include 15%–19% loss to follow-up at 6 months on the co-primary outcomes, as anticipated; the number of secondary outcome measures in our trial, which may increase the risk of a type I error; and potential low statistical power to demonstrate significant between-group differences on important secondary patient-reported outcomes. Conclusions In this study, we observed improved mobility in people with a wide range of health conditions making use of digitally enabled rehabilitation, whereas time spent upright was not impacted. Trial registration The trial was prospectively registered with the Australian New Zealand Clinical Trials Register; ACTRN12614000936628, In a randomised controlled trial, Leanne Hassett and colleagues investigate the impact of digitally-enabled aged care and neurological rehabilitation on activity and mobility outcomes in Australia., Author summary Why was this study done? A higher dose of therapy in physical rehabilitation is associated with better outcomes; however, current rehabilitation models deliver low therapy doses. Use of digital devices such as virtual reality video games, activity monitors, and handheld computer devices can be enjoyable, provide feedback on performance, and may enable a greater dose of task-specific therapy to improve outcomes. Current evidence is yet to confidently confirm the effects of rehabilitation using digital devices in addition to usual rehabilitation care on mobility tasks such as walking and other important outcomes such as quality of life. What did the researchers do and find? In a pragmatic, outcome-assessor-blinded randomised controlled trial, 300 people with walking difficulties (age 72 ± 16 years, 50% female) received usual multidisciplinary inpatient and post-hospital aged care and neurological rehabilitation alone, or in addition used a range of affordable devices such as virtual reality video games, activity monitors, and handheld devices to target mobility and physical activity, as individually prescribed by a physiotherapist for 6 months. On average participants in the intervention group used 4 ± 1 devices in the inpatient setting and 2 ± 1 devices in the post-hospital setting. This approach was feasible and enjoyed, and demonstrated it could be provided across care settings including the post-hospital setting with mostly remote support. Clinically important improvement was seen in mobility at 3 weeks and 6 months after baseline, but this was not accompanied by greater time spent upright. No adverse events were reported by participants whilst undertaking rehabilitation using digital devices, and there was no difference in the rate of falls between groups. What do these findings mean? Digitally enabled rehabilitation using a range of devices prescribed by a physiotherapist to target a range of mobility limitations across care settings for adults with mixed health conditions can improve mobility but not time spent upright. These results need to be interpreted in light of study limitations including a 15%–19% loss to follow-up at 6 months on the co-primary outcomes. Future models of rehabilitation should investigate incorporating digital devices to enhance inpatient and post-hospital rehabilitation, but prescription should ensure quality and quantity of practice.

Paper wasps (Polistes dominula), parasitized by the strepsipteran Xenos vesparum, are castrated and desert the colony to gather on plants where the parasite mates and releases primary larvae, thus completing its lifecycle. One of these plants is the trumpet creeper Campsis radicans: in a previous study the majority of all wasps collected from this plant were parasitized and focused their foraging activity on C. radicans buds. The unexpected prevalence and unusual feeding strategy prompted us to investigate the influence of this plant on wasp behavior and physiology through a multidisciplinary approach. First, in a series of laboratory bioassays, we observed that parasitized wasps spent more time than non-parasitized ones on fresh C. radicans buds, rich of extra-floral nectaries (EFNs), while the same wasps ignored treated buds that lacked nectar drops. Then, we described the structure and ultra-structure of EFNs secreting cells, compatible with the synthesis of phenolic compounds. Subsequently, we analysed extracts from different bud tissues by HPLC-DAD-MS and found that verbascoside was the most abundant bioactive molecule in those tissues rich in EFNs. Finally, we tested the immune-stimulant properties of verbascoside, as the biochemical nature of this compound indicates it might function as an antibacterial and antioxidant. We measured bacterial clearance in wasps, as a proxy for overall immune competence, and observed that it was enhanced after administration of verbascoside—even more so if the wasp was parasitized. We hypothesize that the parasite manipulates wasp behavior to preferentially feed on C. radicans EFNs, since the bioactive properties of verbascoside likely increase host survival and thus the parasite own fitness.

Amphimeriasis, a fish-borne zoonotic disease caused by the liver fluke Amphimerus spp., has recently been reported as an emerging disease affecting an indigenous Ameridian group, the Chachi, living in Ecuador. The only method for diagnosing amphimeriasis was the microscopic detection of eggs from the parasite in patients' stool samples with very low sensitivity. Our group developed an ELISA technique for detection of anti-Amphimerus IgG in human sera and a molecular method based on LAMP technology (named LAMPhimerus) for specific and sensitive parasite DNA detection. The LAMPhimerus method showed to be much more sensitive than classical parasitological methods for amphimeriasis diagnosis using human stool samples for analysis. The objective of this work is to demonstrate the feasibility of using dried stool samples on filter paper as source of DNA in combination with the effectiveness of our previously designed LAMPhimerus assay for successfully Amphimerus sp. detection in clinical stool samples. A total of 102 untreated and undiluted stool samples collected from Chachi population were spread as thin layer onto common filter paper for easily transportation to our laboratory and stored at room temperature for one year until DNA extraction. When LAMPhimerus method was applied for Amphimerus sp. DNA detection, a higher number of positive results was detected (61/102; 59.80%) in comparison to parasitological methods (38/102; 37.25%), including 28/61 (45.90%) microscopy-confirmed Amphimerus sp. infections. The diagnostic parameters for the sensitivity and specificity werecalculated for our LAMPhimerus assay, which were 79.17% and 65.98%, respectively. We demonstrate, for the first time, that common filter paper is useful for easy collection and long-term storage of human stool samples for later DNA extraction and molecular analysis of human-parasitic trematode eggs. This simple, economic and easily handling method combined with the specific and sensible LAMPhimerus assay has the potential to beused as an effective molecular large-scale screening test for amphimeriasis-endemic areas.