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Background People with suspected prostate cancer are usually offered either a local anaesthetic transrectal ultrasound-guided prostate biopsy or a general anaesthetic transperineal prostate biopsy. Transperineal prostate biopsy is often carried out under general anaesthetic due to pain caused by the procedure. However, recent studies suggest that performing local anaesthetic transperineal prostate biopsy may better identify cancer in particular regions of the prostate and reduce infection rates, while being carried out in an outpatient setting. Devices to assist with freehand methods of local anaesthetic transperineal prostate may also help practitioners performing prostate biopsies. Objectives To evaluate the clinical effectiveness and cost-effectiveness of local anaesthetic transperineal prostate compared to local anaesthetic transrectal ultrasound-guided prostate and general anaesthetic transperineal prostate biopsy for people with suspected prostate cancer, and local anaesthetic transperineal prostate with specific freehand devices in comparison with local anaesthetic transrectal ultrasound-guided prostate and transperineal prostate biopsy conducted with a grid and stepping device conducted under local or general anaesthetic. Data sources and methods We conducted a systematic review of studies comparing the diagnostic yield and clinical effectiveness of different methods for performing prostate biopsies. We used pairwise and network meta-analyses to pool evidence on cancer detection rates and structured narrative synthesis for other outcomes. For the economic evaluation, we reviewed published and submitted evidence and developed a model to assess the cost-effectiveness of the different biopsy methods. Results We included 19 comparative studies (6 randomised controlled trials and 13 observational comparative studies) and 4 single-arm studies of freehand devices. There were no statistically significant differences in cancer detection rates for local anaesthetic transperineal prostate (any method) compared to local anaesthetic transrectal ultrasound-guided prostate (relative risk 1.00, 95% confidence interval 0.85 to 1.18) (n = 5 randomised controlled trials), as was the case for local anaesthetic transperineal prostate with a freehand device compared to local anaesthetic transrectal ultrasound-guided prostate (relative risk 1.40, 95% confidence interval 0.96 to 2.04) (n = 1 randomised controlled trial). Results of meta-analyses of observational studies were similar. The economic analysis indicated that local anaesthetic transperineal prostate is likely to be cost-effective compared with local anaesthetic transrectal ultrasound-guided prostate (incremental cost below £20,000 per quality-adjusted life-year gained) and less costly and no less effective than general anaesthetic transperineal prostate. local anaesthetic transperineal prostate with a freehand device is likely to be the most cost-effective strategy: incremental cost versus local anaesthetic transrectal ultrasound-guided prostate of £743 per quality-adjusted life-year for people with magnetic resonance imaging Likert score of 3 or more at first biopsy. Limitations There is limited evidence for efficacy in detecting clinically significant prostate cancer. There is comparative evidence for the PrecisionPoint™ Transperineal Access System (BXTAccelyon Ltd, Burnham, UK) but limited or no evidence for the other freehand devices. Evidence for other outcomes is sparse. The cost-effectiveness results are sensitive to uncertainty over cancer detection rates, complication rates and the numbers of core samples taken with the different biopsy methods and the costs of processing them. Conclusions Transperineal prostate biopsy under local anaesthetic is equally efficient at detecting prostate cancer as transrectal ultrasound-guided prostate biopsy under local anaesthetic but it may be better with a freehand device. local anaesthetic transperineal prostate is associated with urinary retention type complications, whereas local anaesthetic transrectal ultrasound-guided prostate has a higher infection rate. local anaesthetic transperineal prostate biopsy with a freehand device appears to meet conventional levels of costeffectiveness compared with local anaesthetic transrectal ultrasound-guided prostate. Study registration This study is registered as PROSPERO CRD42021266443. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR134220) and is published in full in Health Technology Assessment Vol. 28, No. 60. See the NIHR Funding and Awards website for further award information. Plain language summary A prostate biopsy can help determine if a person has prostate cancer. The main ways of performing a prostate biopsy involve taking small samples of the prostate out through the rectum (back passage) or through the perineum – the skin area between the anus and the scrotum (testicles). Both methods use ultrasound images from a probe inserted into the rectum to help the clinician see what they are doing. Taking samples through the rectum is usually carried out under local anaesthetic, whereas taking samples through the perineum is usually carried out under general anaesthetic. We wanted to find out if taking samples through the perineum under local anaesthetic (instead of general anaesthetic) would be equally effective at detecting prostate cancer as the other biopsy methods and whether there was any improvement or change in the sorts of side effects people may have. We also wanted to know if people found the biopsy painful or not. We carried out searches of computer research databases to find relevant clinical and cost-effectiveness studies and compared the effectiveness of the different biopsy methods they used. We read and summarised the results of the studies we found in our search. Our findings showed that taking biopsy samples through the perineum under local anaesthetic had rates of detecting prostate cancer similar to those of the other biopsy methods. But if the clinician also used a freehand device that helps guide the biopsy needle as part of the procedure, then this may be a better method for detecting cancer. The studies we found agreed that performing this prostate biopsy under local anaesthetic was not too painful for most people. Our economic estimates suggest that using a freehand device for local anaesthetic perineal (through the skin of the perineum) biopsy may be a cost-effective use of National Health Service resources. Scientific summary Background Prostate cancer accounts for 30% of all cancers diagnosed in men in the UK and the incidence is rising. It is more common in men over 45 years of age. Symptoms that cannot be attributed to other health conditions include lower back or bone pain, lethargy, erectile dysfunction, haematuria, weight loss and lower urinary tract symptoms. National Institute for Health and Care Excellence (NICE) guideline NG12 advises on recognition and referral of people presenting with possible prostate cancer. A prostate-specific antigen (PSA) test and digital rectal examination should be performed. If PSA levels are raised above normal or if the prostate feels malignant, then the person should be referred for suspected cancer. NICE guideline NG131 advises on diagnosis and management. It recommends a multiparametric magnetic resonance imaging (mpMRI) test with the results reported using a five-point Likert scale to indicate how likely the presence of prostate cancer is. The Likert scale score, or alternatively the Prostate Imaging Reporting and Data System (PI-RADS score, not mentioned in the NICE guideline), is used to assess whether the person is offered a prostate biopsy. People with a score of 3 or above should be offered a multiparametric magnetic resonance imaging (mpMRI)-influenced prostate biopsy. People with a score of 1 or 2 will discuss risks and benefits with a clinician and if a prostate biopsy goes ahead, it should be a systematic biopsy. Two main options for biopsy are transrectal ultrasound prostate biopsy under local anaesthetic (LATRUS) and transperineal prostate biopsy under general anaesthetic (GATP). Biopsies can be either targeted (based on mpMRI findings) or systematic (samples are taken according to a predefined scheme) or both. Recent studies suggest that performing transperineal prostate biopsy under local anaesthetic (LATP) could better identify cancer in particular regions of the prostate and could have lower infection rates than transrectal biopsies while also being able to be carried out in an outpatient setting. Transperineal prostate biopsy is usually carried out under general anaesthetic due to pain caused by the procedure and tolerability is a key issue. Various freehand devices to assist with LATP prostate biopsy are being introduced to the market. The six specific freehand devices specified in the NICE scope for this review are: Cambridge Prostate Biopsy Device (CamPROBE) (JEB Technologies Ltd, Suffolk, UK); EZU-PA3U (Hitachi Ltd, Tokyo, Japan); PrecisionPoint™ Transperineal Access System (BXTAccelyon Ltd, Burnham, UK); SureFire Guide (LeapMed, Jiangsu, China); Trinity® Perine Grid (KOELIS®, NJ, USA); UA1232 puncture attachment (BK Medical, MA, USA). Objectives The aim of this review is to evaluate the diagnostic yield, clinical effectiveness and cost-effectiveness of LATP prostate biopsies performed with or without available specialist devices and equipment, in people with suspected prostate cancer. Two decision questions were prioritised by NICE for this assessment, with input from relevant stakeholders: Decision question 1. Do LATP prostate biopsies in patients with suspected prostate cancer represent a clinically and cost-effective use of National Health Service (NHS) resources? Decision question 2. Do freehand transperineal biopsy devices for LATP prostate biopsies in patients with suspected prostate cancer represent a clinically effective and cost-effective use of NHS resources? There are five comparisons required to address the two decision questions in the NICE scope: LATP-any (using coaxial needle or grid and stepping device or freehand device) versus LATRUS LATP-any (using coaxial needle or grid and stepping device or freehand device) versus GATP LATP-freehand (freehand device only) versus LATRUS LATP-freehand (freehand device only) versus GATP LATP-freehand (freehand device only) versus LATP-grid and stepping device. Methods Systematic review of diagnostic test evaluation and clinical effectiveness A systematic review of diagnostic and clinical effectiveness evidence was conducted following a peer-reviewed protocol. Searches were based on a comprehensive search strategy. Bibliographic databases, including MEDLINE, EMBASE, Web of Science, The Cochrane Library and the International HTA database, were searched for English-language references in July 2021, and these searches were updated at the end of October 2021. Urology conferences and freehand-device company submissions were hand-searched, and reference lists of identified systematic reviews and meta-analyses were checked. Relevant studies were sought through contact with study authors and NICE Specialist Committee members. Studies were eligible if they included people with suspected prostate cancer with an indication for prostate biopsy and reported diagnostic yield, for example, cancer detection rates, or other clinical or patient-reported outcomes. The eligible interventions were any LATP biopsy (of which LATP-freehand biopsy is a subset) and the eligible comparators were LATRUS and GATP; the LATP-grid and stepping device was an eligible comparator when compared with the LATP-freehand intervention. The Cochrane risk of bias tool (version 1) was used to assess risk of bias for the included randomised controlled trials (RCTs) and The Joanna Briggs Institute critical appraisal checklists were used to assess the included observational studies. Two reviewers carried out study selection, data extraction and critical appraisal, with any disagreements resolved through discussion and referred to a third reviewer for resolution as necessary. We conducted meta-analysis of the cancer detection rate outcomes for which sufficient comparative data were available. Pairwise meta-analysis was conducted for the above comparisons, with randomised and non-randomised studies analysed separately. Network meta-analysis was conducted for the two decision questions specified in the NICE scope. We synthesised the data for other outcomes narratively, as evidence was too sparse for meta-analysis. Review of economic evaluations We conducted a systematic review of the cost-effectiveness of the prostate biopsy methods in scope. The search strategies were based on an early version of the clinical effectiveness searches with the addition of an economics search filter. Included studies were full economic evaluations that assessed both costs and consequences for the different prostate biopsy methods. Outcomes included measures of resource use and costs and health outcomes: life-years or quality-adjusted life-years (QALYs) gained. Economic evaluations not meeting the inclusion criteria and studies that reported on resource use and costs, and health-related quality of life (utilities) were assessed as potential sources of information for the economic model. External Assessment Group independent economic assessment We developed a decision model to estimate the cost-effectiveness of alternative biopsy methods for people referred for biopsy with suspected prostate cancer. The model includes a decision tree to estimate diagnostic outcomes and biopsy-related complications, and a Markov model that predicts the long-term costs and consequences of false-negative biopsy results. We assessed cost-effectiveness for four subgroups at different prior levels of risk, based on previous mpMRI results (Likert 1 or 2; or Likert 3 or more) and history of prostate biopsy (none; previous negative biopsy). The decision tree used published results from the economic evaluation of the Prostate MR imaging study (PROMIS) to estimate baseline prevalence in the subgroups of interest, and diagnostic yield of LATRUS biopsy. Cancer detection rates were adjusted for the other biopsy methods using relative risks (RRs) from our network meta-analyses, and evidence from the literature on biopsy complication rates and the probability of repeat biopsy. Costs of the biopsy methods were estimated in a microcosting analysis, as well as from submitted evidence and published sources. The Markov model was a replicated version of a model developed for the 2019 update of the NICE guideline (NG131). Model parameters were based on those in the NG131 model, with some adjustments to costs and utilities from more recent published sources. Results Systematic review of diagnostic test evaluation and clinical effectiveness The literature searches identified a total of 1969 references of which 111 references were subjected to full-text screening. Twenty-seven publications reported 23 studies meeting the inclusion criteria for this review: 19 comparative studies of which 6 were RCTs and 13 were observational studies (1 of which is unpublished); and 4 single-arm studies for LATP-freehand devices where no comparative evidence was identified. There were no statistically significant differences in cancer detection rates for LATP (any method) compared to LATRUS with RR = 1.00 [95% confidence interval (CI) 0.85 to 1.18] (n = 5 RCTs). A single randomised trial estimated a non-significant difference in cancer detection rates in favour of LATP using a freehand device (PrecisionPoint) compared to LATRUS RR = 1.40, 95% CI 0.96 to 2.04. This finding was supported by meta-analysis of observational comparative studies RR = 1.21 (95% CI 1.08 to 1.34) (n = 4 studies). There were no statistically significant differences in cancer detection rates in meta-analyses comparing other biopsy methods. Evidence from the systematic review for other clinical outcomes, biopsy-related complications and patient-reported outcomes was sparse. Review of economic evaluations One economic evaluation was eligible for inclusion in the economic review out of 725 results from the original and update searches. This study evaluated the CamPROBE (LATP-freehand) device versus LATRUS for use in diagnosing prostate cancer from the perspective of the UK NHS. It used a decision-tree model with a Markov model at the terminal nodes and was informed by a prospective case series for the CamPROBE device and data from the PROMIS study. The study suggested that compared with LATRUS, LATP using the CamPROBE freehand device would be cost saving at a device price below £41 per procedure, or more cost-effective at the £20,000 per QALY threshold with a price below £81 per procedure. These calculations assume a zero rate of infection for LATP and equal diagnostic accuracy for LATP using CamPROBE and LATRUS. We considered 13 excluded economic studies as sources to inform our model structure and inputs, including the cost-effectiveness analysis for the PROMIS study and the analysis for the update of the NICE guideline on prostate cancer published in May 2019 (NG131). Evidence from the BXTAccelyon company submission included a cost minimisation study developed in 2020 by the York Health Consortium that compared the costs of LATP (with the PrecisionPoint freehand device) with different combinations of LATRUS and GATP for UK NHS Trusts. The study suggests that LATP using the PrecisionPoint freehand device is cost saving, assuming equal diagnostic yield of the different biopsy methods. Independent economic assessment The base-case economic analysis comparing LATP (all methods) with LATRUS and GATP indicated that LATP is likely to be the most cost-effective option in all four subgroups, with incremental cost-effectiveness ratio (ICER) estimates for LATP compared with LATRUS below £20,000 per QALY gained, and GATP estimated as more expensive and less effective than LATP. These conclusions were supported by probabilistic sensitivity analysis and a wide range of scenario analyses, although the results for LATP compared with LATRUS were sensitive to some alternative sources of cancer detection rates, rates of biopsy-related hospital admissions, numbers of core samples and histopathology costs. The economic analysis including LATP-freehand compared with other LATP methods, as well as LATRUS and GATP, indicated that LATP with a freehand device was the most cost-effective strategy, with an ICER of £743 per QALY for the highest-risk subgroup with MRI Likert score of 3 or more at first biopsy, and £4595 per QALY for the subgroup with a MRI Likert score 1 or 2 at first biopsy. For the subgroups with a previous negative biopsy, the ICER remained below £20,000 per QALY. Again, probabilistic sensitivity analysis supported these results, but scenario analysis highlighted uncertainty related to the cost of the devices, the number of core samples and costs of processing them, and the use of other sources of evidence for cancer detection and biopsy-related complication rates. The more favourable cost-effectiveness estimates for LATP with a freehand device are mostly driven by the cancer detection rates, which rest on a single RCT for LATP with a freehand device (PrecisionPoint). In the scenario based on observational evidence of cancer detection rates, the ICERs for LATP with a freehand device were less favourable, although still well below £20,000 per QALY. Increasing the cost of LATP with a freehand device by assuming the cost of the most expensive device, the ICER remained below £20,000 per QALY for the highest-risk subgroup but not for the other subgroups. Conclusions Transperineal prostate biopsy under local anaesthetic is equally efficient at detecting prostate cancer as transrectal ultrasound-guided prostate biopsy under local anaesthetic but evidence from one RCT, supported by observational studies, suggests that it might be better when using a freehand device. Local anaesthetic transperineal prostate biopsy is associated with urinary retention-type complications, whereas local anaesthetic transrectal ultrasound-guided prostate biopsy has a higher infection rate. Economic evaluation suggests that LATP with a freehand device is likely to be cost-effective compared with LATP with other methods, LATRUS and GATP for patients with no previous biopsy at high risk of having prostate cancer indicated by previous MRI results. This result is sensitive to the estimated cost of the freehand device, the number of and cost of core samples taken, and the sources for biopsy complication rates. Recommendations for research Evidence for freehand devices. There was no comparative evidence for several of the freehand devices in the NICE scope. The TRANSLATE study is expected to help address this question, as it is evaluating the PrecisionPoint, UA1232 and ‘any ultrasound probe-mounted needle guidance device’. Outcomes not covered in included available evidence. We suggest that incidence of defined complications (standardised for grading of severity and length of follow-up), health-related quality of life and longer-term clinical outcomes could be defined in a core outcome set. LATP versus GATP. Evidence for this comparison is sparse (we identified one RCT reporting cancer detection rates). Repeat biopsy population. There is a need for separate reporting of results for this subgroup, or a separate prospective RCT. UK NHS setting. The three UK studies included in our review were single-centre observational studies with a limited set of outcomes. The TRANSLATE study is expected to remedy this; it is a multicentre randomised study across nine NHS Trusts in England. Study registration This study is registered as PROSPERO CRD42021266443. Funding This awardproject was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR134220) and is published in full in Health Technology Assessment Vol. 28, No. 60. See the NIHR Funding and Awards website for further award information.

The retina transforms patterns of light into visual feature representations supporting behaviour. These representations are distributed across various types of retinal ganglion cells (RGCs), whose spatial and temporal tuning properties have been studied extensively in many model organisms, including the mouse. However, it has been difficult to link the potentially nonlinear retinal transformations of natural visual inputs to specific ethological purposes. Here, we discover a nonlinear selectivity to chromatic contrast in an RGC type that allows the detection of changes in visual context. We trained a convolutional neural network (CNN) model on large-scale functional recordings of RGC responses to natural mouse movies, and then used this model to search in silico for stimuli that maximally excite distinct types of RGCs. This procedure predicted centre colour opponency in transient suppressed-by-contrast (tSbC) RGCs, a cell type whose function is being debated. We confirmed experimentally that these cells indeed responded very selectively to Green-OFF, UV-ON contrasts. This type of chromatic contrast was characteristic of transitions from ground to sky in the visual scene, as might be elicited by head or eye movements across the horizon. Because tSbC cells performed best among all RGC types at reliably detecting these transitions, we suggest a role for this RGC type in providing contextual information (i.e. sky or ground) necessary for the selection of appropriate behavioural responses to other stimuli, such as looming objects. Our work showcases how a combination of experiments with natural stimuli and computational modelling allows discovering novel types of stimulus selectivity and identifying their potential ethological relevance.

En el presente artículo se realizó una revisión a la propuesta de lineamientos para el ordenamiento turístico de microterritorios, misma que tenía como fin establecer las bases para una nueva metodología de planificación orientada a los barrios (microterritorios). Para ello se propuso una metodología exploratoria, en la cual se fueron construyendo las bases para el ordenamiento de microterritorios a través de tres ejes principales. Un diagnóstico subdividido en componentes: turístico, social y ambiental, cada uno con sus propios indicadores y evaluaciones. La información para su construcción se recopiló a través de observación directa y compilación de información. El segundo eje es la localización satelital y categorización de microespacios. Los microespacios se obtienen en base a la información del diagnóstico y son partes integrales de un microterritorio, para su construcción se usó Google Earth. El tercer eje son estrategias para el fortalecimiento del microterritorio; en este apartado se brindan ideas que sirvan a los tomadores de decisiones del barrio estudiado. El microterritorio San Juan, ubicado en el Centro Histórico de Quito, fue seleccionado para el desarrollo de la propuesta. Los resultados obtenidos señalan que el barrio San Juan cuenta con potencial para desarrollar la actividad turística, una base social importante y una buena diversidad natural. Estos aspectos fueron traducidos en la creación de cuatro microespacios y la elaboración de estrategias variadas que van desde alumbrado público hasta arborización de la zona. En conclusión, se reafirma que la propuesta es factible; sin embargo, se deben corregir aspectos como la extensión de la misma, cambiar ciertos indicadores de evaluación o aumentar otros microespacios.

Background Patients access relevant information concerning their orthopaedic surgery resources through multiple information channels before presenting for clinical treatment. Recently, artificial intelligence (AI)-powered chatbots have become another source of information for patients. The currently developed AI chat technology ChatGPT (OpenAI LP) is an application for such purposes and it has been rapidly gaining popularity, including for patient education. This study sought to evaluate whether ChatGPT can correctly answer frequently asked questions (FAQ) regarding periprosthetic joint infection (PJI). Methods Twelve FAQs about PJI after hip and knee arthroplasty were identified from the websites of fifteen international clinical expert centres. ChatGPT was confronted with these questions and its responses were analysed for their accuracy using an evidence-based approach by a multidisciplinary team. Responses were categorised in four groups: (1) Excellent response that did not require additional improvement; (2) Satisfactory responses that required a small amount of improvement; (3) Satisfactory responses that required moderate improvement; and (4) Unsatisfactory responses that required a large amount of improvement. Results From the analysis of the responses given by the chatbot, no reply received an ‘unsatisfactory’ rating; one did not require any correction; and the majority of the responses required low (7 out of 12) or moderate (4 out of 12) clarification. Although a few responses required minimal clarification, the chatbot responses were generally unbiased and evidence-based, even when asked controversial questions. Conclusions The AI-chatbot ChatGPT was able to effectively answer the FAQs of patients seeking information around PJI diagnosis and treatment. The given information was also written in a manner that can be assumed to be understandable by patients. The chatbot could be a valuable clinical tool for patient education and understanding around PJI treatment in the future. Further studies should evaluate its use and acceptance by patients with PJI.

Abstract Background Residual disease following cytoreductive surgery in patients with ovarian cancer has been associated with poorer survival outcomes compared with no residual disease. We performed a meta-analysis to assess the impact of varying levels of residual disease status on survival outcomes in patients with ovarian cancer who have undergone primary cytoreductive surgery or interval cytoreductive surgery in the setting of new therapies for this disease. Methods Medline, Embase, and Cochrane databases (January 2011 – July 2020) and grey literature, bibliographic and key conference proceedings, were searched for eligible studies. Fixed and random-effects meta-analyses compared progression and survival by residual disease level across studies. Heterogeneity between comparisons was explored via type of surgery, disease stage, and type of adjuvant chemotherapy. Results Of 2832 database and 16 supplementary search articles screened, 50 studies were selected; most were observational studies. The meta-analysis showed that median progression-free survival and overall survival decreased progressively with increasing residual disease (residual disease categories of 0 cm, > 0–1 cm and > 1 cm). Compared with no residual disease, hazard ratios (HR) for disease progression increased with increasing residual disease category (1.75 [95% confidence interval: 1.42, 2.16] for residual disease > 0–1 cm and 2.14 [1.34, 3.39] for residual disease > 1 cm), and also for reduced survival (HR versus no residual disease, 1.75 [ 1.62, 1.90] for residual disease > 0–1 cm and 2.32 [1.97, 2.72] for residual disease > 1 cm). All comparisons were significant (p

Las universidades enfrentan desafíos complejos y cambiantes, desde aspectos tecnológicos hasta cambios geopolíticos. La falta de un modelo adaptado podría resultar en ineficiencias. Por lo tanto, crear un modelo de gestión específico es esencial para garantizar la eficacia y sostenibilidad en este entorno educativo en constante evolución. El objetivo principal del artículo fue analizar estos retos, e identificar las tendencias tecnológicas, sociales, geopolíticas y ambientales, con la finalidad de proponer un modelo de gestión para universidades glonacales. La metodología utilizada fue de tipo cuantitativa de alcance descriptivo y de corte transversal, para lo cual en la fase inicial se realizó una revisión bibliográfica para la construcción de los instrumentos de recolección de datos. La técnica utilizada fue la encuesta, estructurada por 46 ítems que alcanzaron un coeficiente de confiabilidad de 0,932 tanto para el instrumento como para cada uno de los elementos. A través de un censo participación 362 miembros de una universidad del Ecuador, entre docentes y directivos expertos en los ejes de docencia, investigación y gestión. En conclusión, se propone un modelo de gestión, que se caracteriza por su enfoque en la flexibilidad, adaptabilidad, visión estratégica, compromiso con la excelencia académica y la colaboración con la comunidad. Este modelo alcanzo un índice de validez de contenido de 0,875, que es alto y sugiere que se considera como relevante.

As plastic pollution continues to persist at a global level, the Arctic has drawn increased research interest as a possible sink for marine pollutants. Plastic and microplastics are highly durable and can be transported across vast distances. To date, only a handful of studies have directly assessed microplastics in Arctic mammals. In Canada, it is still unclear whether they show a concrete propensity for microplastic retention and ingestion. Atlantic walruses (Odobenus rosmarus rosmarus (Linnaeus, 1758)) are economically and culturally important for Inuit and are key predators in Arctic marine ecosystems. Here, we present the first assessment of microplastic pollution in Canadian walruses and the first gastrointestinal assessment of microplastic in walruses globally. Since microplastics accumulate in benthic sediment and animals, we expected that walruses may ingest and retain microplastic contaminants when sifting in search of prey or when eating contaminated bivalves and invertebrates. We detected no microplastics ≥80 µm in our evaluation of 36 walruses from five communities in NU, Canada. Our results suggest that walruses in this region do not retain microplastic particles ≥80 µm in their stomachs, which is consistent with findings in other pinnipeds that have been evaluated in Arctic Canada.

BackgroundSocial media (SM) has been recognized as a professional communication tool in the field of orthopedic and trauma surgery that can enhance communication with patients and peers, and increase the visibility of research and offered services. The specific purposes of professional SM use and the benefits and concerns among orthopedic and trauma surgeons, however, remain unexplored. ObjectiveThis study aims to demonstrate the specific uses of different SM platforms among orthopedic and trauma surgeons in Germany as well as the advantages and concerns. MethodsA web-based questionnaire was developed on the use of SM in a professional context by considering the current literature and the authors’ topics of interest. The final questionnaire consisted of 33 questions and was distributed among German orthopedic and trauma surgeons via the mail distributor of the Berufsverband für Orthopädie und Unfallchirurgie (Professional Association of Orthopaedic Surgeons in Germany). The study was conducted between June and July 2022. A subgroup analysis was performed for sex (male vs female), age (

A partir de entrevistas realizadas en el banco analizado y la revisión de su documentación de desempeño ambiental, se identificaron sus principales iniciativas para reducir su impacto ambiental y el de sus clientes. En particular se reseña la estrategia de “biocrédito” y se presentan sus resultados en tres indicadores: reducción de emisiones de CO2, reducción de consumo de agua y reducción de consumo de energía. Los resultados se tomaron de los reportes de las certificadoras ambientales que revisan la gestión del banco, de la verificación realizada por parte de auditores y de su memoria de sostenibilidad. Se hallaron importantes niveles de reducción en los tres indicadores, lo que confirma la necesidad de implementar estas iniciativas en la banca de manera más generalizada y sostenida.

Actualmente los diversos cambios en las conductas y preferencias de los estudiantes han generado una amplia variedad de opciones al momento de seleccionar un programa de cuarto nivel. Ello obliga a las universidades, centros de estudios, escuelas profesionales, entre otros organismos nacionales e internacionales, a buscar alternativas para la captación de potenciales aspirantes, sumando a esto el desarrollo tecnológico, retos profesionales y amplia oferta educativa es indispensable determinar las principales variables que intervienen al momento de acceder a un programa de cuarto nivel. Resulta de gran relevancia entender el rol que cumplen los maestrantes y las herramientas que les facilitará adquirir nuevas competencias, habilidades y experiencias mediante recursos tecnológicos en escenarios de apoyo virtual y seguimiento educativo. Mediante un estudio mixto se realizó un análisis cuantitativo implementando una encuesta a los estudiantes graduados de las universidades ecuatorianas, complementando la investigación con un estudio descriptivo, el que permitió determinar las variables que inciden en la selección de un programa de maestría o especialización de cuarto nivel. Asimismo, aportan un eje de desarrollo para las instituciones ofertantes de programas de cuarto nivel optimizando su oferta académica con relación al prestigio institucional, perfil profesional deseado, mallas innovadoras, modalidad de estudio y nivel de inglés. Para una validación exitosa del programa escogido es aconsejable considerar sus ventajas y desventajas, tiempos y facilidades que ofrezcan las instituciones de educación superior siendo asesorados en cada momento con trasparencia y ética para tomar una decisión más beneficiosa.

Background: Brain Health Index (BHI) assimilates various MRI sequences, giving a quantitative measure of brain health. To date, BHI validation has been cross-sectional and limited to selected populations. Further large-scale validation and assessment of temporal change is required to understand its clinical utility. Aim: Assess 1) relationships between variables associated with cognitive decline and BHI 2) associations between BHI and measures of cognition and 3) longitudinal changes in BHI and relationship with cognitive function. Methods: BHI computation involved Gaussian mixture-model cluster analysis of T1, T2, T2*, and T2 FLAIR MRI data from participants within the European Prevention of Alzheimer's Dementia (EPAD) cohort. Group differences (gender- and health-based) were evaluated using independent samples Welch's t-tests. Relationships between BHI, age and cognitive tests used linear regression. Longitudinal analysis (12/24 months) utilised mixed linear regression models to examine BHI changes, and paired BHI/cognition associations. Results: Data from N = 1496 predominantly Caucasian participants (50–88 years old, 43.32% male) were used. BHI scores were lower in those with diabetes (p < 0.001, d = 0.419), hypertension (p < 0.001, d = 0.375), hypercholesterolemia (p < 0.001, d = 0.193) and stroke (p < 0.05, d = 0.512). APOE was not significantly related to BHI scores. After correction for age, cross-sectional BHI scores were significantly associated with all measures of cognitive function in males, but only the Four Mountains Test (4MT) in females. Longitudinal change in BHI and cognition were not consistently related. Conclusions: BHI is a valid marker of cognitive decline and relatively stable over 1-2 year follow-up periods. Further work should assess temporal changes over a longer duration and determine relationships between BHI and cognition in more diverse populations.

Introduction Ovarian hyperstimulation syndrome (OHSS) is the most significant short-term complication of pharmacological ovarian stimulation. Symptoms range from mild abdominal discomfort to rare complications such as renal failure, thromboembolism and respiratory distress syndrome.Currently, clinical practice typically involves monitoring the patient until the condition becomes severe, at which point they are admitted to hospital, where drainage of ascitic fluid (paracentesis) may take place. Preliminary studies have indicated that earlier outpatient paracentesis may reduce the progression of OHSS and prevent hospitalisation in women.Methods and analysis This UK, multicentre, pragmatic, two-arm, parallel-group, adaptive (group sequential with one interim analysis), open-label, superiority, confirmatory, group sequential, individually randomised controlled trial, with internal pilot will assess the clinical and cost-effectiveness and safety of outpatient paracentesis versus conservative management (usual care) for moderate or severe OHSS. 224 women from 20 National Health Service and private fertility units will be randomised (1:1) and followed up for up to 13.5 months. The primary outcome is the rate of OHSS related hospital admission of at least 24 hours within 28 days postrandomisation. The primary analysis will be an intention to treat with difference in hospitalisation rates as measure of treatment effect. Secondary outcomes include time to resolution of symptoms, patient satisfaction, adverse events and cost-effectiveness. A qualitative substudy will facilitate the feasibility of recruitment. Participant recruitment commenced in June 2022.Ethics and dissemination London—Southeast Research Ethics Committee approved the protocol (reference: 22/LO/0015). Findings will be submitted to peer-reviewed journals and abstracts to relevant national and international conferences, as well as being disseminated to trial participants and patient groups.Trial registration number ISRCTN71978064.

IntroductionSupplementation with increased inspired oxygen fractions has been suggested to alleviate the harmful effects of tissue hypoxia during hemorrhagic shock (HS) and traumatic brain injury. However, the utility of therapeutic hyperoxia in critical care is disputed to this day as controversial evidence is available regarding its efficacy. Furthermore, in contrast to its hypoxic counterpart, the effect of hyperoxia on the metabolism of circulating immune cells remains ambiguous. Both stimulating and detrimental effects are possible; the former by providing necessary oxygen supply, the latter by generation of excessive amounts of reactive oxygen species (ROS). To uncover the potential impact of increased oxygen fractions on circulating immune cells during intensive care, we have performed a 13C-metabolic flux analysis (MFA) on PBMCs and granulocytes isolated from two long-term, resuscitated models of combined acute subdural hematoma (ASDH) and HS in pigs with and without cardiovascular comorbidity.MethodsSwine underwent resuscitation after 2 h of ASDH and HS up to a maximum of 48 h after HS. Animals received normoxemia (PaO2 = 80 – 120 mmHg) or targeted hyperoxemia (PaO2 = 200 – 250 mmHg for 24 h after treatment initiation, thereafter PaO2 as in the control group). Blood was drawn at time points T1 = after instrumentation, T2 = 24 h post ASDH and HS, and T3 = 48 h post ASDH and HS. PBMCs and granulocytes were isolated from whole blood to perform electron spin resonance spectroscopy, high resolution respirometry and 13C-MFA. For the latter, we utilized a parallel tracer approach with 1,2-13C2 glucose, U-13C glucose, and U-13C glutamine, which covered essential pathways of glucose and glutamine metabolism and supplied redundant data for robust Bayesian estimation. Gas chromatography-mass spectrometry further provided multiple fragments of metabolites which yielded additional labeling information. We obtained precise estimations of the fluxes, their joint credibility intervals, and their relations, and characterized common metabolic patterns with principal component analysis (PCA).Results13C-MFA indicated a hyperoxia-mediated reduction in tricarboxylic acid (TCA) cycle activity in circulating granulocytes which encompassed fluxes of glutamine uptake, TCA cycle, and oxaloacetate/aspartate supply for biosynthetic processes. We further detected elevated superoxide levels in the swine strain characterized by a hypercholesterolemic phenotype. PCA revealed cell type-specific behavioral patterns of metabolic adaptation in response to ASDH and HS that acted irrespective of swine strains or treatment group.ConclusionIn a model of resuscitated porcine ASDH and HS, we saw that ventilation with increased inspiratory O2 concentrations (PaO2 = 200 – 250 mmHg for 24 h after treatment initiation) did not impact mitochondrial respiration of PBMCs or granulocytes. However, Bayesian 13C-MFA results indicated a reduction in TCA cycle activity in granulocytes compared to cells exposed to normoxemia in the same time period. This change in metabolism did not seem to affect granulocytes’ ability to perform phagocytosis or produce superoxide radicals.

Abstract Background Due to the Covid-19 pandemic, on-site classroom teaching became limited at most German medical universities. This caused a sudden demand for digital teaching concepts. How the transfer from classroom to digital teaching or digitally assisted teaching was conducted was decided by each university and/or department individually. As a surgical discipline, Orthopaedics and Trauma have a particular focus on hands-on teaching as well as direct contact to patients. Therefore, specific challenges in designing digital teaching concepts were expected to arise. Aim of this study was to evaluate medical teaching at German universities one year into the pandemic as well as to identify potentials and pitfalls in order to develop possible optimization approaches. Methods A questionnaire with 17 items was designed and sent to the professors in charge of organising the teaching in Orthopaedics and Trauma at each medical university. A differentiation between Orthopaedics and Trauma was not made to allow a general overview. We collected the answers and conducted a qualitative analysis. Results We received 24 replies. Each university reported a substantial reduction of their classroom teaching and efforts to transfer their teaching to digital formats. Three sites were able to switch to digital teaching concepts completely, whereas others tried to enable classroom and bedside teaching at least for students of higher edcuational levels. The online platforms used varied depending on the university as well as the format it was supposed to support. Conclusion One year into the pandemic significant differences concerning the proportions of classroom and digital teaching for Orthopaedics and Trauma can be observed. Simultaneously huge differences in concepts used to create digital teaching are present. Since a complete suspense of classroom teaching was never mandatory, several universities developed hygiene concepts to enable hands-on and bedside teaching. Despite these differences, some similarities were observed: the lack of time and personnel to generate adequate teaching material was reported as the leading challenge by all participants of this study.

The complement system plays a crucial role in host defense, homeostasis, and tissue regeneration and bridges the innate and the adaptive immune systems. Although the genetic variants in complement C2 (c.839_849+17del; p.(Met280Asnfs*5)) and C8B (c.1625C>T; p.(Thr542Ile)) are known individually, here, we report on a patient carrying their combination in a heterozygous form. The patient presented with a reduced general condition and suffers from a wide variety of autoimmune diseases. While no autoimmune disease-specific autoantibodies could be detected, genetic analysis revealed abnormalities in the two complement genes C2 and C8B. Therefore, we performed a comprehensive investigation of the innate immune system on a cellular and humoral level to define the functional consequences. We found slightly impaired functionality of neutrophils and monocytes regarding phagocytosis and reactive oxygen species generation and a diminished expression of the C5aR1. An extensive complement analysis revealed a declined activation potential for the alternative and classical pathway. Reconstitution with purified C2 and C8 into patient serum failed to normalize the dysfunction, whereas the addition of C3 improved the hemolytic activity. In clinical transfer, in vitro supplementation of the patient’s plasma with FFP as a complement source could fully restore full complement functionality. This study describes for the first time a combined heterozygous genetic variation in complement C2 and C8B which, however, cannot fully explain the overall dysfunctions and calls for further complement deficiency research and corresponding therapies.

Abstract Background Although apps are becoming increasingly relevant in healthcare, there is limited knowledge about how healthcare professionals perceive “quality” in this context and how quality principles that can aid them in assessing health-related apps may be prioritised. The objective was to investigate physicians’ views of predefined (general) quality principles for health apps and to determine whether a ranking algorithm applied to the acquired data can provide stable results against various demographic influences and may thus be appropriate for prioritisation. Methods Participants of an online survey of members of two German professional orthopaedics associations conducted between 02/12/2019 and 02/01/2020 were asked about their perception of a set of quality principles for health apps (i.e., “practicality,” “risk adequacy,” “ethical soundness,” “legal conformity,” “content validity,” “technical adequacy,” “usability,” “resource efficiency,” and “transparency”). Structured as a Kano survey, for each principle, there were questions about its perceived relevance and opinions regarding the presence or absence of corresponding characteristics. The available data were evaluated descriptively, and a newly developed method for prioritisation of the principles was applied overall and to different demographic strata (for validation). Results Three hundred eighty-two datasets from 9503 participants were evaluated. Legal conformity, content validity, and risk adequacy filled ranks one to three, followed by practicability, ethical soundness, and usability (ranks 4 to 6). Technical adequacy, transparency, and resource efficiency ranked last (ranks 7 to 9). The ranking based on the proposed method was relatively stable, irrespective of demographic factors. The principles were seen as essential, with one exception (“resource efficiency”). Only those with little to no interest in digitisation (22/382, 5.8%) rated the nine principles indifferently. Conclusions The specified quality principles and their prioritisation can lay a foundation for future assessments of apps in the medical field. Professional societies build upon this to highlight opportunities for digital transformations in medicine and encourage their members to participate.

La preparación física en el fútbol es crucial para el rendimiento físico, por lo que es necesario estar al tanto de las últimas tendencias sobre los enfoques utilizados a fin de identificar las mejores prácticas y las áreas que requieren perfeccionarse. El objetivo de la investigación consistió en desarrollar una revisión exhaustiva de las tendencias actuales en la preparación física del futbolista profesional. Esta investigación fue de tipo teórica, se aplicó la técnica de revisión documental y el instrumento matriz de registro. Los pasos que se siguieron fueron la búsqueda y selección de artículos relevantes de preparación física, extracción de información, validación de fuentes, organización de hallazgos, identificación de patrones y síntesis narrativa. La investigación reveló las tendencias en la preparación física de los futbolistas y resaltó la importancia de la personalización, la planificación estratégica, el enfoque integral del entrenamiento y la alimentación adecuada. El estudio generó nuevas perspectivas en el campo de la preparación física, permitió una comprensión más completa y actualizada de las tendencias y prácticas en este ámbito, lo que sirve como base para futuras investigaciones y cubre brechas de conocimiento en el campo de la preparación física del futbolista profesional.

BackgroundSocial media (SM) has gained importance in the health care sector as a means of communication and a source of information for physicians and patients. However, the scope of professional SM use by orthopedic and trauma surgeons remains largely unknown. ObjectiveThis study presents an overview of professional SM use among orthopedic and trauma surgeons in Germany in terms of the platforms used, frequency of use, and SM content management. MethodsWe developed a web-based questionnaire with 33 variables and 2 separate sections based on a review of current literature. This study analyzed the first section of the questionnaire and included questions on demographics, type of SM used, frequency of use, and SM content management. Statistical analysis was performed using SPSS (version 26.0). Subgroup analysis was performed for sex, age groups (

Background: The Brain Health Index (BHI) is an automated approach to quantifying brain integrity, combining different types of structural magnetic resonance imaging (MRI). Normative values derived from generally healthy individuals provide a vital baseline for understanding neurodegenerative change. Although commonplace in other areas of medicine, these are not always established when proposing new analytical approaches using MRI. The scale and quality of the UK Biobank imaging cohort (approximately N = 50k, as of 2022) allows for derivation of such values, and the wealth of additional lifestyle, physiological and demographic data enables validation of BHI through comparison with more established variables which may affect brain health. Aim: This study aimed to: 1) establish normative BHI values in a cohort of ‘healthy’ participants, and 2) explore associations between BHI and risk factors for brain health. Methods: The BHI was computed using voxel-based Gaussian mixture model cluster analysis of T1 and T2 FLAIR MRI in a sub-cohort of UK Biobank participants. From these data, normative score curves – with bounds described as 1, 2 and 3 standard deviations from the mean – were produced for males and females, using regression analyses to measure the scale of the BHI values as a function of age. Additional Pearson’s correlation testing was used to examine known risk factors to brain health and their relationship to BHI scores, with t-tests and ANOVAs used to determine between-group differences in BHI scoring. Results: Data from 2,990 participants (50.07% male, 97.05% Caucasian, 43.6% with degree-level education) were used to derive normative BHI curves from 48 to 77 years old. BHI scores were higher in female than male participants (95% CI: 0.0103 to 0.0162, p

Cystic fibrosis (CF) is a monogenetic disease caused by an impairment of the cystic fibrosis transmembrane conductance regulator (CFTR). CF affects multiple organs and is associated with acute and chronic inflammation. In 2020, Elexacaftor–Tezacaftor–Ivacaftor (ETI) was approved to enhance and restore the remaining CFTR functionality. This study investigates cellular innate immunity, with a focus on neutrophil activation and phenotype, comparing healthy volunteers with patients with CF before (T1, n = 13) and after six months (T2, n = 11) of ETI treatment. ETI treatment reduced sweat chloride (T1: 95 mmol/l (83|108) vs. T2: 32 mmol/l (25|62), p < 0.01, median, first|third quartile) and significantly improved pulmonal function (FEV1 T1: 2.66 l (1.92|3.04) vs. T2: 3.69 l (3.00|4.03), p < 0.01). Moreover, there was a significant decrease in the biomarker human epididymis protein 4 (T1: 6.2 ng/ml (4.6|6.3) vs. T2: 3.0 ng/ml (2.2|3.7), p < 0.01) and a small but significant decrease in matrix metallopeptidase 9 (T1: 45.5 ng/ml (32.5|140.1) vs. T2: 28.2 ng/ml (18.2|33.6), p < 0.05). Neutrophil phenotype (CD10, CD11b, CD62L, and CD66b) and function (radical oxygen species generation, chemotactic and phagocytic activity) remained largely unaffected by ETI treatment. Likewise, monocyte phenotype and markers of platelet activation were similar at T1 and T2. In summary, the present study confirmed a positive impact on patients with CF after ETI treatment. However, neither beneficial nor harmful effects of ETI treatment on cellular innate immunity could be detected, possibly due to the study population consisting of patients with well-controlled CF.

Considerable interest has centered on Earth-like planets orbiting in the circumstellar habitable zone (CHZ) of its star. However, the potential habitability of an exoplanet depends upon a number of additional factors, including the presence and strength of any planetary magnetic field and the interaction of this field with that of the host star. Not only must the exoplanet have a strong enough magnetic field to shield against stellar activity, but it must also orbit far enough from the star to avoid direct magnetic connectivity. We characterize stellar activity by the star’s Rossby number, Ro, the ratio of stellar rotation rate to convective turnover time. We employ a scaled model of the solar magnetic field to determine the star’s Alfvén radius, the distance at which the stellar wind becomes super-Alfvénic. Planets residing within the Alfvén surface may have a direct magnetic connection to the star and therefore not be the most viable candidates for habitability. Here, we determine the Rossby number of a sample of 1053 exoplanet-hosting stars for which the rotation rates have been observed and for which a convective turnover time can be calculated. We find that 84 exoplanets in our sample have orbits which lie inside the CHZ and that also lie outside the star’s Alfvén surface: 34 of these have been classified as terran (11) or superterran (23) planets. Applying the Alfvén surface habitability criterion yields a subset of the confirmed exoplanets that may be optimal targets for future observations in the search for signatures of life.

Research Question: How will the Substance-over-Form (SoF) ‘organism’ survive, mutate and develop in a new and unfamiliar ‘environment’? Motivation: Our study is motivated and inspired from a previous study published by Alexander et al. (2018) on “philosophy of language and accounting”. Alexander et al. (2018) used the “Substance-over-Form” principle as a case study investigation of the practicability, or non-practicability, of harmonising changes in accounting regulation across seven countries (and six languages). The objective of this paper is to investigate on a very different context: Albania (an EU candidate country, an ex-communist “Balkan state”, a different socially-constructed reality). Idea: This analysis shows the evolution of the SoF concept, by emphasizing the importance of the translation of official documents from English to Albanian and vice versa, comparing the content, the quality, and the level of translation in accounting. Data: We first analysed the main Albanian legislations on accounting from 1990 (opening year of the country to the free market economy) until 2021. Then, in order to assess the quality of translation from English to Albanian, we also critically examined the content and the level of translation of the 2018 IASB Conceptual Framework for Financial Reporting. Tools: The paper follows a deductive approach, as the results come from contextual data or clauses. A manual content analysis is implemented. Subsequently, a critical semantic analysis and an in-depth investigation on the level of translation of the accounting concepts, with an explicit focus on SoF treatment, is performed. Findings: The exposition, analysis and results are fully consistent with our theoretical framework, “social Darwinism”. We add the Albanian case to previous studies, providing a contrasting scenario in that Albania has a significantly different history over recent decades. We illustrate a different socially-constructed reality from the seven countries of Alexander et al. (2018), and extend the overall understanding and the overall picture. The Albanian “organism” (accounting GAAP system) is consistent with its socially-constructed reality/environment. SoF seems to be distorted in its passage from Directive/IFRS originating sources, and this may well be fully consistent with local needs, realities, and cultures. Contribution: This research contributes to academic debate in three ways. First, it adds evidence to the literature on harmonisation processes, analysing the evolution of financial reporting regulation for a specific country and the application of a fundamental concept, such as SoF, comparing it to other national regulations. Second, this work contributes to further research, being a pioneer for the application of the “social Darwinism” to the analysis of a GAAP system. Finally, the paper contributes to the development of research on translation issues in accounting, by technically analysing the level of translation of the IASB Conceptual Framework for Financial Reporting and back-translating from national Laws.

Abstract Background To ensure successful medical education despite the COVID-19 pandemic, the demand for online instruction has substantially increased. Fast and efficient teaching in a digital format poses a great challenge for medical students and lecturers as well as the universities. Objective The aim of this study is to capture the readiness of medical students and faculty members to participate in rapidly- evolving online education. Methods This cross-sectional study is based on two questionnaires distributed among medical students and associate deans for education in Germany, Austria and Switzerland. Questions included decision- making questions, categorical questions, and open-ended questions, all addressing the frequency and format of the digital education offered, the perceived quality of digital education, and medical student satisfaction with digital education. Questions about missing content and areas for improvement from the perspectives of medical students were included. The associate deans were asked for their opinions about the impact of the pandemic on teaching, the organizational setup and implementation of digital education by universities, and plans for future initiatives. Results Three thousand and thirty medical students (m = 752 and f = 2245) from 53 universities participated in the study. The study showed that 92% of students were affected by the pandemic, and 19% of the students viewed the changes as entirely negative. 97% of the medical students were able to participate in digital courses, but only 4% were able to learn exclusively online. For 77% of the medical students, digital offerings accounted for over 80% of the education offered. In terms of content, medical students complained about a lack of practical teaching, such as contact with patients, lecturers, fellow medical students, and a poor perceived quality of teaching due to dubbing, frequent changeover of seminars, problem-oriented learning groups and in-person teaching, a lack of interaction possibilities and a lack of technical equipment, such as lecturers’ knowledge and server capacities, at the universities. Overall, almost half of the medical students (42%) rated the implementation of digital teaching at their universities as good or very good. Forty-one of the 53 associate deans responded to the questionnaire, and 35 felt medical education was influenced by the pandemic. The associate deans (80%; 33/41) felt that the digitalization of medical education was negatively influenced by the pandemic. Only 44% (18/41) felt that their universities were well or very well positioned for digital teaching. All the associate deans believe that digital teaching in medicine will continue after the pandemic. Conclusions In the German-speaking world, the rapid conversion of medical teaching to a digital format has been well implemented in many cases. The perceived quality of the implementation of digital education still lacks practical relevance and the use of new digital media, such as learning games, VR, and online question time. The digital format of medical education will likely continue beyond the COVID-19 pandemic.

BackgroundEfficient digitization in medicine still is in its infancy but undeniably has great potential for current and future challenges in health care. Thus far, the rollout of medical apps has not resulted in widespread use of smartphones in the German health care sector—the reasons for this have not been clarified so far. Nevertheless, the lack of user involvement in the development process and content creation might contribute to low acceptance of these products. ObjectiveThis study aims to outline an approach to involve medical expertise without any coding knowledge for developing medical app content and functions. MethodsAn end user–operable backend was built. Its usability was evaluated using a usability evaluation test protocol. The results of the usability tests were evaluated by the app development team, and the usability test was repeated for optimizing backend usability. In total, 40 criteria to measure the ease of app usage were defined a priori. The usability test comprised 20 tasks that had to be fulfilled. Usability tasks were analyzed for completion, dropout, and test duration. Due to the COVID-19 pandemic, digital videoconferencing platforms (Zoom and QuickTime Player) were used to complete usability questionnaires. Finally, several backend-based apps for several specialties (infectiology, plastic and reconstructive surgery, and orthopedics) were developed by health care professionals as prototypes. ResultsInitial usability testing was conducted with 5 participants (4 men and 1 woman; mean age 39.2, SD 5.97 years). All of them could complete the assigned backend tasks with only a few workflow interruptions and some minor errors. After usability optimization, the workflow completion time decreased from 5.03 minutes to 3.50 minutes, indicating a time saving. The basic backend structure was clear to all test users and the handling was intuitive to learn. Some minor errors in the backend occurred during the test rounds. The apps developed using the aforementioned approach are in clinical use as a proof of concept. ConclusionsBackends offering operability for medical professionals might have great potential for app development in the mobile health sector. Sophisticated and time-saving usability are pivotal for the acceptance of medical software, as illustrated by the backend-based apps presented herein, which are in clinical use as a proof of concept. Basic interventions are essential and sufficient for adequate usability optimization. Practicable, well-structured software usability evaluation is possible based on the usability evaluation test protocol.

BackgroundThe majority of Germans see a deficit in information availability for choosing a physician. An increasing number of people use physician rating websites and decide upon the information provided. In Germany, the most popular physician rating website is Jameda.de, which offers monthly paid membership plans. The platform operator states that paid memberships have no influence on the rating indicators or list placement. ObjectiveThe goal of this study was to investigate whether a physician’s membership status might be related to his or her quantitative evaluation factors and to possibly quantify these effects. MethodsPhysician profiles were retrieved through the search mask on Jameda.de website. Physicians from 8 disciplines in Germany’s 12 most populous cities were specified as search criteria. Data Analysis and visualization were done with Matlab. Significance testing was conducted using a single factor ANOVA test followed by a multiple comparison test (Tukey Test). For analysis, the profiles were grouped according to member status (nonpaying, Gold, and Platinum) and analyzed according to the target variables—physician rating score, individual patient’s ratings, number of evaluations, recommendation quota, number of colleague recommendations, and profile views. ResultsA total of 21,837 nonpaying profiles, 2904 Gold, and 808 Platinum member profiles were acquired. Statistically significant differences were found between paying (Gold and Platinum) and nonpaying profiles in all parameters we examined. The distribution of patient reviews differed also by membership status. Paying profiles had more ratings, a better overall physician rating, a higher recommendation quota, and more colleague recommendations, and they were visited more frequently than nonpaying physicians’ profiles. Statistically significant differences were found in most evaluation parameters within the paid membership packages in the sample analyzed. ConclusionsPaid physician profiles could be interpreted to be optimized for decision-making criteria of potential patients. With our data, it is not possible to draw any conclusions of mechanisms that alter physicians’ ratings. Further research is needed to investigate the causes for the observed effects.

Abstract Reactive inkjet printing (RIJ) is demonstrated as a new approach to the patterning of surfaces with metal–organic frameworks (MOFs). RIJ is an emerging manufacturing technique that jets solutions of reagents onto a substrate allowing them to react in situ to form the desired material. MOFs have the potential to perform a variety of useful sensing, catalytic, separation and storage applications within sophisticated devices, however, their insolubility makes them challenging to process into complex shapes and patterns. The RIJ approach offers advantages over conventional inkjet printing in that it allows stable solutions of different ligand and metal ions to be combined in a “mix‐and‐match” way. Here, the benefits of the RIJ approach are demonstrated to optimize the stoichiometry of the printed MOF, print a variety of different frameworks using common inks, and create gradients where the composition of the printed MOFs gradually varies between one isoreticular structure and another. Proof of principle is also demonstrated for the approach by demonstrating size selective encapsulation of a dye within a RIJ printed MOF. It is anticipated that this approach will be broadly applicable to the printing of MOFs and related materials enhancing their use across a variety of different applications.

In 2010, southern Iceland's Eyjafjallajökull volcano erupted, releasing ash that spread across Europe. Due to its potential to damage aircraft, much of European airspace was closed for six days. Known problems were brought to the forefront regarding the anticipation of and response to systemic risks. To contribute a deeper understanding of this situation, this paper explores this disaster through its fundamental causes and cascading impacts, highlighting perspectives from disaster risk reduction, complexity sciences, and health in order to support analysis and resolution of systemic risks. Two principal future directions emerge from this work. First, how to manage dependency on air travel. Second, how to think about and act to avert future calamities.

Severe physical injuries and associated traumatic brain injury and/or hemorrhagic shock (HS) remain leading causes of death worldwide, aggravated by accompanying extensive inflammation. Retrospective clinical data indicated an association between mild hyperoxemia and improved survival and outcome. However, corresponding prospective clinical data, including long-term resuscutation, are scarce. Therefore, the present study explored the effect of mild hyperoxemia for 24 hours in a prospective randomized controlled trial in a long-term resuscitated model of combined acute subdural hematoma (ASDH) and HS. ASDH was induced by injecting 0.1 ml × kg−1 autologous blood into the subdural space and HS was triggered by passive removal of blood. After 2 hours, the animals received full resuscitation, including retransfusion of the shed blood and vasopressor support. During the first 24 hours, the animals underwent targeted hyperoxemia (PaO2 = 200 – 250 mmHg) or normoxemia (PaO2 = 80 – 120 mmHg) with a total observation period of 55 hours after the initiation of ASDH and HS. Survival, cardiocirculatory stability, and demand for vasopressor support were comparable between both groups. Likewise, humoral markers of brain injury and systemic inflammation were similar. Multimodal brain monitoring, including microdialysis and partial pressure of O2 in brain tissue, did not show significant differences either, despite a significantly better outcome regarding the modified Glasgow Coma Scale 24 hours after shock that favors hyperoxemia. In summary, the present study reports no deleterious and few beneficial effects of mild targeted hyperoxemia in a clinically relevant model of ASDH and HS with long-term resuscitation in otherwise healthy pigs. Further beneficial effects on neurological function were probably missed due to the high mortality in both experimental groups. The present study remains exploratory due to the unavailability of an a priori power calculation resulting from the lack of necessary data.

Summary: Background: People who experience an ischaemic stroke are at risk of recurrent vascular events, progression of cerebrovascular disease, and cognitive decline. We assessed whether allopurinol, a xanthine oxidase inhibitor, reduced white matter hyperintensity (WMH) progression and blood pressure (BP) following ischaemic stroke or transient ischaemic attack (TIA). Methods: In this multicentre, prospective, randomised, double-blinded, placebo-controlled trial conducted in 22 stroke units in the United Kingdom, we randomly assigned participants within 30-days of ischaemic stroke or TIA to receive oral allopurinol 300 mg twice daily or placebo for 104 weeks. All participants had brain MRI performed at baseline and week 104 and ambulatory blood pressure monitoring at baseline, week 4 and week 104. The primary outcome was the WMH Rotterdam Progression Score (RPS) at week 104. Analyses were by intention to treat. Participants who received at least one dose of allopurinol or placebo were included in the safety analysis. This trial is registered with ClinicalTrials.gov, NCT02122718. Findings: Between 25th May 2015 and the 29th November 2018, 464 participants were enrolled (232 per group). A total of 372 (189 with placebo and 183 with allopurinol) attended for week 104 MRI and were included in analysis of the primary outcome. The RPS at week 104 was 1.3 (SD 1.8) with allopurinol and 1.5 (SD 1.9) with placebo (between group difference −0.17, 95% CI −0.52 to 0.17, p = 0.33). Serious adverse events were reported in 73 (32%) participants with allopurinol and in 64 (28%) with placebo. There was one potentially treatment related death in the allopurinol group. Interpretation: Allopurinol use did not reduce WMH progression in people with recent ischaemic stroke or TIA and is unlikely to reduce the risk of stroke in unselected people. Funding: The British Heart Foundation and the UK Stroke Association.

El tema de la táctica en el deporte resulta polémico desde los puntos de vista científico y pedagógico. En la investigación presentada, se realizó un análisis teórico de los principales estudios que abordaron el término acción táctica. La psicología, como ciencia aplicada al deporte, tiene entre sus fines la preparación psicológica y dentro de esta la realización del control psicológico del deportista; en esta dirección, se pretendió conocer las manifestaciones de las variables psicológicas de rendimiento durante todo el proceso de entrenamiento deportivo y contribuir, a partir de sus métodos diversos de intervención, al desarrollo de habilidades para enfrentar cualquier obstáculo objetivo o subjetivo durante la competencia. Se concluyó que, para mayor beneficio en intervenciones psicológicas en el área del desempeño técnico-táctico, se debe tener en cuenta el término acción táctica, el abordaje de los términos técnicos y tácticos como unidad indisoluble, la identificación de los elementos técnico-tácticos significativos que forman parte de las características del deporte y las personológicas del deportista; además de, los enfoques teóricos que sirvieron de sustento para el desarrollo del estudio.

IntroductionSodium thiosulfate (Na2S2O3), an H2S releasing agent, was shown to be organ-protective in experimental hemorrhage. Systemic inflammation activates immune cells, which in turn show cell type-specific metabolic plasticity with modifications of mitochondrial respiratory activity. Since H2S can dose-dependently stimulate or inhibit mitochondrial respiration, we investigated the effect of Na2S2O3 on immune cell metabolism in a blinded, randomized, controlled, long-term, porcine model of hemorrhage and resuscitation. For this purpose, we developed a Bayesian sampling-based model for 13C isotope metabolic flux analysis (MFA) utilizing 1,2-13C2-labeled glucose, 13C6-labeled glucose, and 13C5-labeled glutamine tracers.MethodsAfter 3 h of hemorrhage, anesthetized and surgically instrumented swine underwent resuscitation up to a maximum of 68 h. At 2 h of shock, animals randomly received vehicle or Na2S2O3 (25 mg/kg/h for 2 h, thereafter 100 mg/kg/h until 24 h after shock). At three time points (prior to shock, 24 h post shock and 64 h post shock) peripheral blood mononuclear cells (PBMCs) and granulocytes were isolated from whole blood, and cells were investigated regarding mitochondrial oxygen consumption (high resolution respirometry), reactive oxygen species production (electron spin resonance) and fluxes within the metabolic network (stable isotope-based MFA).ResultsPBMCs showed significantly higher mitochondrial O2 uptake and lower O2•− production in comparison to granulocytes. We found that in response to Na2S2O3 administration, PBMCs but not granulocytes had an increased mitochondrial oxygen consumption combined with a transient reduction of the citrate synthase flux and an increase of acetyl-CoA channeled into other compartments, e.g., for lipid biogenesis.ConclusionIn a porcine model of hemorrhage and resuscitation, Na2S2O3 administration led to increased mitochondrial oxygen consumption combined with stimulation of lipid biogenesis in PBMCs. In contrast, granulocytes remained unaffected. Granulocytes, on the other hand, remained unaffected. O2•− concentration in whole blood remained constant during shock and resuscitation, indicating a sufficient anti-oxidative capacity. Overall, our MFA model seems to be is a promising approach for investigating immunometabolism; especially when combined with complementary methods.

The pandemic raised a discussion about the postponement of medical interventions for non-small cell lung cancer (NSCLC). We analyzed the characteristics of pretreatment diagnostic assessment in the pandemic and the influence of diagnostic assessment on outcomes. A total of 96 patients with stereotactic body radiation therapy (SBRT) for NSCLC were included. The number of patients increased from mean 0.9 (2012–2019) to 1.45 per month in the COVID era (p < 0.05). Pandemic-related factors (contact reduction, limited intensive care unit resources) might have influenced clinical decision making towards SBRT. The time from pretreatment assessment (multidisciplinary tumor board decision, bronchoscopy, planning CT) to SBRT was longer during the COVID period (p < 0.05). Reduced services, staff shortage, or appointment management to mitigate infection risks might explain this finding. Overall survival, progression-free survival, locoregional progression-free survival, and distant progression-free survival were superior in patients who received a PET/CT scan prior to SBRT (p < 0.05). This supports that SBRT guidelines advocate the acquisition of a PET/CT scan. A longer time from PET/CT scan/conventional staging to SBRT (p < 0.05). The postponement of diagnostic or therapeutic measures in the pandemic should be discussed cautiously. Patient- and tumor-related features should be evaluated in detail.

BackgroundSurface compatibility with blood is critical both for scientific investigations on hemostasis and clinical applications. Regarding in vitro and ex vivo investigations, minimal alteration in physiological hemostasis is of particular importance to draw reliable conclusions on the human coagulation system. At the same time, artificial coagulation activation must be avoided, which is relevant for the patient, for example to prevent stent graft occlusion. The aim was to evaluate the advantages and disadvantages of antithrombotic and antifouling surface coatings in the context of their suitability for ex vivo incubation and the study of coagulation properties.MethodsWe investigated the impact of different protocols for surface coating of synthetic material and different anticoagulants on hemostasis and platelet activation in ex vivo human whole blood. Blood samples from healthy donors were incubated in coated microtubes on a rotating wheel at 37°C. Two protocols for surface coating were analyzed for hemostatic parameters and metabolic status, a heparin-based coating (CHC, Corline Heparin Conjugate) without further anticoagulation and a passivating coating (MPC, 2-methacryloyloxethyl phosphorylcholine) with added anticoagulants (enoxaparin, ENOX; or fondaparinux, FPX). Employing the MPC-based coating, the anticoagulants enoxaparin and fondaparinux were compared regarding their differential effects on plasmatic coagulation by thrombelastometry and on platelet activation by flowcytometry and platelet function assays.ResultsUsing the CHC coating, significant coagulation cascade activation was observed, whereas parameters remained mostly unchanged with MPC-based protocols. Extended incubation caused significantly elevated levels of the soluble membrane attack complex. Neither ENOX nor FPX caused a relevant impairment of platelet function or activation capacity and thrombelastometric parameters remained unchanged with both protocols. For translational purposes, we additionally modeled endotoxemia with the MPC-based protocols by incubating with lipopolysaccharide plus/minus thrombin. While coagulation parameters remained unchanged, elevated Interleukin 8 and Matrix Metalloproteinase 9 demonstrated preserved immune cell responsiveness.ConclusionsThe MPC-based protocols demonstrated better hemocompatibility compared to CHC, and ENOX and FPX proved useful for additional anticoagulation. Furthermore, this simple-to-use whole blood model may be useful for experimental analyses of the early coagulatory and immunological response without decalcification.

BackgroundKnife crime has increased considerably in recent years in Northern Europe. Affected patients often require immediate surgical care due to traumatic organ injury. Yet, little is known about clinically relevant routine laboratory parameters in stab injury patients and how these are associated with intensive care unit (ICU) admission, hospitalization and number of surgeries.MethodsWe retrospectively analyzed 258 stab injury cases between July 2015 and December 2021 at an urban Level I Trauma Center. Annual and seasonal incidences, injury site, injury mechanism, Injury Severity Score (ISS), and surgical management were evaluated. First, correlations between routine laboratory parameters for hematology, coagulation, and serum biochemistry (peak, and Δ (change from admission to peak within 3 days following admission)) and length of hospital stay, ICU stay, and number of surgeries were assessed using Spearman’s rank correlation coefficients. Second, multivariable Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were conducted to identify parameters predictive of clinical outcomes. Third, longitudinal developments of routine laboratory parameters were assessed during hospital admission.ResultsIn 2021, significantly more stab injuries were recorded compared with previous years and occurred less during winter compared with other seasons. Mean ISS was 8.3 ± 7.3, and ISS was positively correlated with length of hospital and ICU stay (r = 0.5–0.8, p < 0.001). Aspartate transaminase (AST) (Δ) (r = 0.690), peak C-reactive protein (CrP) (r = 0.573), and erythrocyte count (Δ) (r = 0.526) showed the strongest positive correlations for length of ICU stay for penetrating, thoracoabdominal, and organ injuries, respectively. No correlations were observed between routine laboratory parameters and number of surgeries. For patients with penetrating injuries, LASSO-selected predictors of ICU admission included ISS, pH and lactate at admission, and Δ values for activated partial thromboplastin time (aPTT), K+, and erythrocyte count. CrP levels on day 3 were significantly higher in patients with penetrating (p = 0.005), thoracoabdominal (p = 0.041), and organ injuries (p < 0.001) compared with those without.ConclusionOur data demonstrate an increase in stab injury cases in 2021 and an important link between changes in routine laboratory parameters and ICU admission and hospitalization. Monitoring ISS and changes in AST, CrP, erythrocyte count, pH, lactate, aPTT, and K+ may be useful to identify patients at risk and adjust surgical and ICU algorithms early on.

ObjectiveFacing a shortage of young surgeons, this study aimed to examine the availability of mentoring programs and if this can counteract this lack.Summary background dataMedical mentoring programs have proven to be decisive to influence students’ later career decisions. Since their structure may depend on the medical school and the effort of single disciplines, the offers are often very heterogeneous.MethodsAnonymous online-questionnaires were developed and distributed among medical students in Germany and the dean for teaching of the medical schools from July 2019 to January 2020 in Germany. Data of the availability of mentoring programs, their structure and the impact of surgery were collected.ResultsForty three medical schools participated, with 65% offering mentoring programs. 18 of medical schools had no additional funding available for this. Surgical subjects participated in these programs in only 30%. Additionally, 1,516 medical students participated in the second survey. A total of 70% had already participated in a mentoring program with a significantly higher proportion of men. Of these, 94% stated that this was helpful and had an impact on their career planning, without any gender differences. 95% would participate in structured surgical mentoring programs and 95% agreed that this could have an impact on their career planning.ConclusionMentoring programs may be able to influence career planning, nevertheless participation by surgical specialties has been low. Becoming more active in providing mentoring programs with a special focus on women and offering more surgical content can be a way to counteract the lack of surgical trainees.

Introduction Persistent physical symptoms (which cannot be adequately attributed to physical disease) affect around 1 million people (2% of adults) in the UK. They affect patients’ quality of life and account for at least one third of referrals from General Practitioners (GPs) to specialists. These referrals give patients little benefit but have a real cost to health services time and diagnostic resources. The symptoms clinic has been designed to help people make sense of persistent physical symptoms (especially if medical tests have been negative) and to reduce the impact of symptoms on daily life.Methods and analysis This pragmatic, multicentre, randomised controlled trial will assess the clinical and cost-effectiveness of the symptoms clinic intervention plus usual care compared with usual care alone. Patients were identified through GP searches and mail-outs and recruited by the central research team. 354 participants were recruited and individually randomised (1:1). The primary outcome is the self-reported Physical Health Questionnaire-15 at 52 weeks postrandomisation. Secondary outcome measures include the EuroQol 5 dimension 5 level and healthcare resource use. Outcome measures will also be collected at 13 and 26 weeks postrandomisation. A process evaluation will be conducted including consultation content analysis and interviews with participants and key stakeholders.Ethics and dissemination Ethics approval has been obtained via Greater Manchester Central Research Ethics Committee (Reference 18/NW/0422). The results of the trial will be submitted for publication in peer-reviewed journals, presented at relevant conferences and disseminated to trial participants and patient interest groups.Trial registration number ISRCTN57050216.

En el Ecuador, las organizaciones que forman parte del sector económico popular y solidario se encuentran registradas de forma individual o colectiva, desarrollando procesos de comercialización, intercambio, consumo y financiamiento de bienes o servicios. Las entidades financieras, sean de la economía popular y solidaria o de la superintendencia de bancos y seguros, se convierten en intermediarios entre los clientes y el uso que estos le den a su dinero, ganando comisiones o intereses por los servicios financieros. El 66.6% de las entidades financieras en el Ecuador corresponden a cooperativas de ahorro y crédito, el 18.6% corresponden a cajas de ahorro, 6.2% bancos comunales, el 5.3% cajas comunales, el 2.9% bancos y el 0.5% a mutualistas de ahorro y crédito. En este sentido, el sistema financiero aporta al clima organizacional con un amplio número de herramientas para el desarrollo de sus colaboradores, de tal modo que el 78% de las grandes empresas en el país manejan un proceso asociativo para los colaboradores que les permita realizar ahorros y crédito, permitiéndoles contar con efectivo y fuentes de financiamiento continuo, estas alianzas permiten a los trabajadores contar con una amplia frontera de posibilidades y fuentes de capital.

IntroductionTreating severely injured patients requires numerous critical decisions within short intervals in a highly complex situation. The coordination of a trauma team in this setting has been shown to be associated with multiple procedural errors, even of experienced care teams. Machine learning (ML) is an approach that estimates outcomes based on past experiences and data patterns using a computer-generated algorithm. This systematic review aimed to summarize the existing literature on the value of ML for the initial management of severely injured patients.MethodsWe conducted a systematic review of the literature with the goal of finding all articles describing the use of ML systems in the context of acute management of severely injured patients. MESH search of Pubmed/Medline and Web of Science was conducted. Studies including fewer than 10 patients were excluded. Studies were divided into the following main prediction groups: (1) injury pattern, (2) hemorrhage/need for transfusion, (3) emergency intervention, (4) ICU/length of hospital stay, and (5) mortality.ResultsThirty-six articles met the inclusion criteria; among these were two prospective and thirty-four retrospective case series. Publication dates ranged from 2000 to 2020 and included 32 different first authors. A total of 18,586,929 patients were included in the prediction models. Mortality was the most represented main prediction group (n = 19). ML models used were artificial neural network ( n = 15), singular vector machine (n = 3), Bayesian network (n = 7), random forest (n = 6), natural language processing (n = 2), stacked ensemble classifier [SuperLearner (SL), n = 3], k-nearest neighbor (n = 1), belief system (n = 1), and sequential minimal optimization (n = 2) models. Thirty articles assessed results as positive, five showed moderate results, and one article described negative results to their implementation of the respective prediction model.ConclusionsWhile the majority of articles show a generally positive result with high accuracy and precision, there are several requirements that need to be met to make the implementation of such models in daily clinical work possible. Furthermore, experience in dealing with on-site implementation and more clinical trials are necessary before the implementation of ML techniques in clinical care can become a reality.

Controversial evidence is available regarding suitable targets for the arterial O2 tension (PaO2) after traumatic brain injury and/or hemorrhagic shock (HS). We previously demonstrated that hyperoxia during resuscitation from hemorrhagic shock attenuated cardiac injury and renal dysfunction in swine with coronary artery disease. Therefore, this study investigated the impact of targeted hyperoxemia in a long-term, resuscitated model of combined acute subdural hematoma (ASDH)-induced brain injury and HS. The prospective randomized, controlled, resuscitated animal investigation consisted of 15 adult pigs. Combined ASDH plus HS was induced by injection of 0.1 ml/kg autologous blood into the subdural space followed by controlled passive removal of blood. Two hours later, resuscitation was initiated comprising re-transfusion of shed blood, fluids, continuous i.v. noradrenaline, and either hyperoxemia (target PaO2 200 – 250 mmHg) or normoxemia (target PaO2 80 – 120 mmHg) during the first 24 h of the total of 54 h of intensive care. Systemic hemodynamics, intracranial and cerebral perfusion pressures, parameters of brain microdialysis and blood biomarkers of brain injury did not significantly differ between the two groups. According to the experimental protocol, PaO2 was significantly higher in the hyperoxemia group at the end of the intervention period, i.e., at 24 h of resuscitation, which coincided with a higher brain tissue PO2. The latter persisted until the end of observation period. While neurological function as assessed using the veterinary Modified Glasgow Coma Score progressively deteriorated in the control group, it remained unaffected in the hyperoxemia animals, however, without significant intergroup difference. Survival times did not significantly differ in the hyperoxemia and control groups either. Despite being associated with higher brain tissue PO2 levels, which were sustained beyond the intervention period, targeted hyperoxemia exerted neither significantly beneficial nor deleterious effects after combined ASDH and HS in swine with pre-existing coronary artery disease. The unavailability of a power calculation and, thus, the limited number of animals included, are the limitations of the study.

Introduction: Obesity is classified as a global epidemic and judged to be the greatest public health threat in Western countries. The tremendously increasing prevalence rates in children lead to morbidity and mortality in adults. In many countries, prevalence has doubled since the 1980s. Other countries show a continuous increase or stagnate at a very high level. Given these regional differences, this study aims to draw a global world map of childhood obesity research, including regional epidemiological characteristics, to comprehensively assess research influences and needs. Methods: In addition to established bibliometric parameters, this study uses epidemiological data to interpret metadata on childhood obesity research from the Web of Science in combination with state-of-the-art visualization methods, such as density equalizing map projections. Results: It was not until the 1990s that belated recognition of the dangerous effects of childhood obesity led to an increase in the number of publications worldwide. In addition, our findings show that countries’ study output does not correlate with epidemiologic rates of childhood obesity. In contrast, the primary driver of the research efforts on childhood obesity appears to be largely driven government funding structures. Discussion/Conclusion: The geographical differences in the epidemiological background of childhood obesity complicate the implementation of transnational research projects and cross-border prevention programs. Effective realization requires a sound scientific basis, which is facilitated by globally valid approaches. Hence, there is a need for information exchange between researchers, policy makers, and private initiatives worldwide.

Abstract There is an ongoing discussion whether hyperoxia, i.e. ventilation with high inspiratory O2 concentrations (FIO2), and the consecutive hyperoxaemia, i.e. supraphysiological arterial O2 tensions (PaO2), have a place during the acute management of circulatory shock. This concept is based on experimental evidence that hyperoxaemia may contribute to the compensation of the imbalance between O2 supply and requirements. However, despite still being common practice, its use is limited due to possible oxygen toxicity resulting from the increased formation of reactive oxygen species (ROS) limits, especially under conditions of ischaemia/reperfusion. Several studies have reported that there is a U-shaped relation between PaO2 and mortality/morbidity in ICU patients. Interestingly, these mostly retrospective studies found that the lowest mortality coincided with PaO2 ~ 150 mmHg during the first 24 h of ICU stay, i.e. supraphysiological PaO2 levels. Most of the recent large-scale retrospective analyses studied general ICU populations, but there are major differences according to the underlying pathology studied as well as whether medical or surgical patients are concerned. Therefore, as far as possible from the data reported, we focus on the need of mechanical ventilation as well as the distinction between the absence or presence of circulatory shock. There seems to be no ideal target PaO2 except for avoiding prolonged exposure (> 24 h) to either hypoxaemia (PaO2 100 mmHg). Moreover, the need for mechanical ventilation, absence or presence of circulatory shock and/or the aetiology of tissue dysoxia, i.e. whether it is mainly due to impaired macro- and/or microcirculatory O2 transport and/or disturbed cellular O2 utilization, may determine whether any degree of hyperoxaemia causes deleterious side effects.

La Diabetes Mellitus tipo 2 (DM2) es una enfermedad crónica relacionada con factores modificables y no modificables. Ha impactado la salud pública en los últimos decenios. El objetivo de este trabajo es determinar los estilos de vida como factor de riesgo asociados a la aparición DM2 en población rural. Por otra parte, la metodología consistió en el estudio de casos y controles para estimar los riesgos asociados (estilos de vida) con la aparición de DM2: 124 sujetos, 62 casos y 62 controles emparejados por sexo y edad. Se incluyen variables sociodemográficas, estilos de vida y comportamiento alimentario. Razón de momios y la prueba Chi cuadrado Mantel-Haenszel permitieron la estimación estadística. El 24,2 % fueron hombres 75,8 % mujeres, con edad media de 62,7 años y como resultado el 91% de mujeres presentaron alto riesgo cardiovascular. Los sujetos (casos) que consumieron alcohol presentaron mayor riesgo, con una odds ratio (OR) de 1,633 (IC95%1,289–8,015), otras drogas, OR1,718 (IC95%1,306-13,697), pupusas, OR 1,898 (CI95%1,914-9,870), postre OR1,928 (CI95%1,713-36,970), bebidas endulzadas, OR1,652 (CI95% 1,372-7,154). Los sujetos (controles) que consumieron alcohol presentaron menor riesgo, OR 0,508 (IC95%1,289–8,015), otras drogas OR 0,406 (IC95% 1,306-13,697), pupusas, OR 0,437 (CI95%1,914-9,870), postre OR 0,242 (CI95%1,713-36,970) y bebidas endulzadas OR 0,527 (CI95% 1,372-7,154). El consumo de verduras-ensaladas y frutas fueron factores protectores para los dos grupos. En conclusión, las mujeres presentaron mayor riesgo cardiovascular (sobrepeso, obesidad grado I y II). El consumo de alcohol, otras drogas, pupusas, postres y bebidas endulzadas presentaron mayor riesgo en los casos y menor en los controles. El consumo de verduras-ensaladas y frutas fueron factores de protección.

We previously demonstrated marked lung-protective properties of the H2S donor sodium thiosulfate (Na2S2O3, STS) in a blinded, randomized, controlled, long-term, resuscitated porcine model of swine with coronary artery disease, i.e., with decreased expression of the H2S-producing enzyme cystathionine-γ-lyase (CSE). We confirmed these beneficial effects of STS by attenuation of lung, liver and kidney injury in mice with genetic CSE deletion (CSE-ko) undergoing trauma-and-hemorrhage and subsequent intensive care-based resuscitation. However, we had previously also shown that any possible efficacy of a therapeutic intervention in shock states depends both on the severity of shock as well as on the presence or absence of chronic underlying co-morbidity. Therefore, this prospective, randomized, controlled, blinded experimental study investigated the effects of the STS in cardiovascular healthy swine. After anesthesia and surgical instrumentation, 17 adult Bretoncelles-Meishan-Willebrand pigs were subjected to 3 hours of hemorrhage by removal of 30% of the blood volume and titration of the mean arterial pressure (MAP) ≈ 40 ± 5 mmHg. Afterwards, the animals received standardized resuscitation including re-transfusion of shed blood, fluids, and, if needed, continuous i.v. noradrenaline to maintain MAP at pre-shock values. Animals were randomly allocated to either receive Na2S2O3 or vehicle control starting 2 hours after initiation of shock until 24 hours of resuscitation. The administration of Na2S2O3 did not alter survival during the observation period of 68 hours after the initiation of shock. No differences in cardio-circulatory functions were noted despite a significantly higher cardiac output, which coincided with significantly more pronounced lactic acidosis at 24 hours of resuscitation in the Na2S2O3 group. Parameters of liver, lung, and kidney function and injury were similar in both groups. However, urine output was significantly higher in the Na2S2O3 group at 24 hours of treatment. Taken together, this study reports no beneficial effect of Na2S2O3 in a clinically relevant model of hemorrhagic shock-and-resuscitation in animals without underlying chronic cardiovascular co-morbidity.

Objective In medical education, biochemistry topics are usually knowledge based, and students often are unaware of their clinical relevance. To improve students’ awareness of the relevance, we integrated communication skills training into biochemistry education. No studies before have examined the difference between peer and standardised patient (SP) role plays where students explain the biochemical background of a disease in patient-centred language. Therefore, we evaluated whether students’ self-perceived competency in Canadian Medical Education Directives for Specialists (CanMEDS) roles and their opinion of the quality of role play differ if the layperson is played by peers or SPs.Methods We randomly assigned medical students in a preclinical semester to one of the two groups. The groups used predefined scripts to role play a physician–parent consultation with either a peer (peer group) or an SP (SP group) in the parent role. Students then assessed the activity’s effects on their competency in CanMEDS roles and motivation and the relevance of the role play. To determine whether students achieved biochemistry learning goals, we evaluated results of a biochemistry exam.Results Students’ self-perceived competency improved in both groups. The SP group rated their competency in the roles ‘Scholar’ and ‘Professional’ significantly higher than the peer group did. The peer group rated their competency in the role of ‘Medical Expert’ significantly higher if they played the role of the parent rather than physician or observer. The SP group agreed more that they were motivated by the role play and wanted to receive more role play-based teaching. The SP group perceived the role play as being realistic and rated the feedback discussion as more beneficial. The examination results were the same in both groups.Conclusion We showed that role plays in a biochemistry seminar improve students’ self-perceived competency. The use of SPs has some advantages, such as being more realistic.

A sufficient response of neutrophil granulocytes stimulated by interleukin (IL)-8 is vital during systemic inflammation, for example, in sepsis or severe trauma. Moreover, IL-8 is clinically used as biomarker of inflammatory processes. However, the effects of IL-8 on cellular key regulators of neutrophil properties such as the intracellular pH (pHi) in dependence of ion transport proteins and during inflammation remain to be elucidated. Therefore, we investigated in detail the fundamental changes in pHi, cellular shape, and chemotactic activity elicited by IL-8. Using flow cytometric methods, we determined that the IL-8-induced cellular activity was largely dependent on specific ion channels and transporters, such as the sodium-proton exchanger 1 (NHE1) and non-NHE1-dependent sodium flux. Exposing neutrophils in vitro to a proinflammatory micromilieu with N-formyl-Met-Leu-Phe, LPS, or IL-8 resulted in a diminished response regarding the increase in cellular size and pH. The detailed kinetics of the reduced reactivity of the neutrophil granulocytes could be illustrated in a near-real-time flow cytometric measurement. Last, the LPS-mediated impairment of the IL-8-induced response in neutrophils was confirmed in a translational, animal-free human whole blood model. Overall, we provide novel mechanistic insights for the interaction of IL-8 with neutrophil granulocytes and report in detail about its alteration during systemic inflammation.

Prothrombotic hereditary risk factors for cerebral vein thrombosis (CVT) are of clinical interest to better understand the underlying pathophysiology and stratify patients for the risk of recurrence. This study explores prothrombotic risk factors in CVT patients. An initial screening in patients of the outpatient clinic of the Department of Transfusion Medicine and Hemostaseology of the University Hospital Erlangen, Germany, revealed 183 patients with a history of CVT. An initial screening identified a number of common prothrombic risk factors, including Factor V Leiden (rs6025) and Prothrombin G20210A (rs1799963). All patients without relevant findings (58 individuals) were invited to participate in a subsequent genetic analysis of 55 relevant genes using next-generation sequencing (NGS). Three intron variants (ADAMTS13: rs28446901, FN1: rs56380797, rs35343655) were identified to occur with a significantly higher frequency in the CVT patient cohort compared to the general European population. Furthermore, the combined prevalence of at least two of four potentially prothrombic variants (FGA (rs6050), F13A1 (rs5985), ITGB3 (rs5918), and PROCR (rs867186)) was significantly higher in the CVT subjects. The possible impact of the identified variants on CVT is discussed.

The Bahá’í Faith is an important case for a discussion on dignity, religion and human rights. Beyond the notions of dignity enshrined in its basic teachings, a core concern of the Bahá’í community is how to build dignity into the pattern of social relations of an emerging global civilization. The oneness of humanity is the core principle around which all Bahá’í teachings revolve, and within this principle is enshrined not only the inherent, God-given nobility and dignity of every individual but also the responsibility of creating new patterns of social relations, forms of community, processes of education, and structures of institutional authority that consciously strive to create a global polity that protects and affirms the dignity of all humans, in all of their diversity. In this paper, we examine the foundations of human dignity in the Bahá’í Faith in four parts. First, we explore the use of the term “dignity” in Bahá’í sacred texts and its relationship to the concepts of “nobility" and “rights”. Second, we examine how Bahá’ís seek to put into practice their conception of dignity through a democratic system of global governance, grounded in processes of consultative deliberation, referred to as the Bahá’í Administrative Order. Third, we highlight how the Bahá’í community is seeking to cultivate conditions of dignity in its current educational endeavours, which seeks to contribute to the betterment of local communities throughout the world. Fourth, we explore the ongoing and centuries-long persecution of the Bahá’ís in Iran to understand the implications of dignity in responding to oppression.