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Bildungsprozesse in der Jugendarbeit können aufgrund ihrer Vielschichtigkeit und Dynamik als komplexe Phänomene bezeichnet werden, deren empirische Erforschung den Blick auf ein Geflecht von Beziehungen und Strukturen erfordert. Um der Komplexität dieses Forschungsgegenstandes angemessen zu begegnen, haben BIEWERS GRIMM, LATZ, WEIS und SAMUEL (2022) in einer Studie am Zentrum für Kindheits- und Jugendforschung der Universität Luxemburg verschiedene qualitative und quantitative Verfahren in einem Mixed-Methods-Design kombiniert. Dieses Vorgehen bei der Datenerhebung und -auswertung ermöglichte es, die Bedingungen und Erfahrungen sowie die expliziten und impliziten Aspekte von Bildung im Alltag der offenen Jugendarbeit aus unterschiedlichen Perspektiven zu beleuchten. In der methodischen Reflexion der Studie zeigte sich, dass diese Ergebnisse aber nicht für eine gegenseitige Validierung genutzt werden konnten, da sie nicht konvergent zueinander waren. Die Qualität der Forschung stellte dies jedoch nicht infrage, denn auch die Komplementarität der Ergebnisse kann dazu beitragen, komplexe Forschungsgegenstände differenziert zu analysieren und tiefere, ganzheitlichere Einsichten zu generieren.

BackgroundAnti-IgLON5 disease is a rare chronic autoimmune disorder characterized by IgLON5 autoantibodies predominantly of the IgG4 subclass. Distinct pathogenic effects were described for anti-IgLON5 IgG1 and IgG4, however, with uncertain clinical relevance.MethodsIgLON5-specific IgG1-4 levels were measured in 46 sera and 20 cerebrospinal fluid (CSF) samples from 13 HLA-subtyped anti-IgLON5 disease patients (six females, seven males) using flow cytometry. Intervals between two consecutive serum or CSF samplings (31 and 10 intervals, respectively) were categorized with regard to the immunomodulatory treatment active at the end of the interval, changes of anti-IgLON5 IgG1 and IgG4 levels, and disease severity. Intrathecal anti-IgLON5 IgG4 synthesis (IS) was assessed using a quantitative method.ResultsThe median age at onset was 66 years (range: 54–75), disease duration 10 years (range: 15–156 months), and follow-up 25 months (range: 0–83). IgLON5-specific IgG4 predominance was observed in 38 of 46 (83%) serum and 11 of 20 (55%) CSF samples. Anti-IgLON5 IgG4 levels prior clinical improvement in CSF but not serum were significantly lower than in those prior stable/progressive disease. Compared to IgLON5 IgG4 levels in serum, CSF levels in HLA-DRB1*10:01 carriers were significantly higher than in non-carriers. Indeed, IgLON5-specific IgG4 IS was demonstrated not only in four of five HLA-DRB1*10:01 carriers but also in one non-carrier. Immunotherapy was associated with decreased anti-IgGLON5 IgG serum levels. In CSF, lower anti-IgLON5 IgG was associated with immunosuppressive treatments used in combination, that is, corticosteroids and/or azathioprine plus intravenous immunoglobulins or rituximab.ConclusionOur findings might indicate that CSF IgLON5-specific IgG4 is frequently produced intrathecally, especially in HLA-DRB1*10:01 carriers. Intrathecally produced IgG4 may be clinically relevant. While many immunotherapies reduce serum IgLON5 IgG levels, more intense immunotherapies induce clinical improvement and may be able to target intrathecally produced anti-IgLON5 IgG. Further studies need to confirm whether anti-IgLON5 IgG4 IS is a suitable prognostic and predictive biomarker in anti-IgLON5 disease.

A avicultura de corte é de extrema importância para a economia brasileira, ocupando o primeiro lugar em exportação de carne de frango do mundo, seguido dos Estados Unidos e União Europeia. A alta produção e consumo foi possível devido avanços no melhoramento genético associado a dieta equilibrada, manejo e bem-estar animal proporcionando aves com maior rendimento de carcaça em um curto espaço de tempo. A elevada produtividade foi alcançada, mas surgiram problemas sanitários que muitas vezes são detectados no processo de abate, levando a condenações parciais ou totais da carcaça e a prejuízos econômicos. O objetivo deste trabalho foi investigar a relação entre a estação climática (verão e inverno) e as principais causas de condenação total ou parcial de frangos em uma linha comercial de abate com Serviço de Inspeção Federal e estimar os prejuízos econômicos. Foram coletados dados de 10 granjas de frangos integradas a um frigorífico localizado no norte do Paraná, no período de 2018 a 2020. Os dados foram agrupados de acordo com a estação climática em verão (n= 1.485.630) e inverno (n=1.077.012). A condenação parcial representou 94,8% no verão e 96,1% no inverno, enquanto que, a condenação total foi de 5,2% para o verão e 3,9% para o inverno. Entre as condenações parciais, a principal causa de condenação foi a atrite (33% para verão e 28% para inverno), contusão (28% para verão e 27,9% para inverno), miopatia (14,7% para verão e 16% para inverno) e fratura (10,3% para verão e 12,6% para inverno). O verão promoveu maiores perdas (p

Objective To evaluate the cost-effectiveness of pessary therapy as an initial treatment option compared with surgery for moderate to severe pelvic organ prolapse (POP) symptoms in secondary care from a healthcare and a societal perspective.Design Economic evaluation alongside a multicentre randomised controlled non-inferiority trial with a 24-month follow-up.Setting 21 hospitals in the Netherlands, recruitment conducted between 2015 and 2022.Participants 1605 women referred to secondary care with symptomatic prolapse stage ≥2 were requested to participate. Of them, 440 women gave informed consent and were randomised to pessary therapy (n=218) or to surgery (n=222) in a 1:1 ratio stratified by hospital.Interventions Pessary therapy and surgery.Primary and secondary outcome measures The Patient Global Impression of Improvement (PGI-I), a 7-point scale dichotomised into successful versus unsuccessful, with a non-inferiority margin of −10%; quality-adjusted life-years (QALYs) measured by the EQ-5D-3L; healthcare and societal costs were based on medical records and the institute for Medical Technology Assessment questionnaires.Results For the PGI-I, the mean difference between pessary therapy and surgery was −0.05 (95% CI −0.14; 0.03) and −0.03 (95% CI −0.07; 0.002) for QALYs. In total, 54.1% women randomised to pessary therapy crossed over to surgery, and 3.6% underwent recurrent surgery. Healthcare and societal costs were significantly lower in the pessary therapy (mean difference=−€1807, 95% CI −€2172; −€1446 and mean difference=−€1850, 95% CI −€2349; −€1341, respectively). The probability that pessary therapy is cost-effective compared with surgery was 1 at willingness-to-pay thresholds between €0 and €20 000/QALY gained from both perspectives.Conclusions Non-inferiority of pessary therapy regarding the PGI-I could not be shown and no statistically significant differences in QALYs between interventions were found. Due to significantly lower costs, pessary therapy is likely to be cost-effective compared with surgery as an initial treatment option for women with symptomatic POP treated in secondary care.Trial registration number NTR4883.

Introduction Herpes simplex virus (HSV) is frequently detected in the respiratory tract of mechanically ventilated patients and is associated with a worse outcome. The aim of this study is to determine whether antiviral therapy in HSV-positive patients improves outcome.Methods and analysis Prospective, multicentre, open-label, randomised, controlled trial in parallel-group design. Adult, mechanically ventilated patients with pneumonia and HSV type 1 detected in bronchoalveolar lavage (≥105 copies/mL) are eligible for participation and will be randomly allocated (1:1) to receive acyclovir (10 mg/kg body weight every 8 hours) for 10 days (or until discharge from the intensive care unit if earlier) or no intervention (control group). The primary outcome is mortality measured at day 30 after randomisation (primary endpoint) and will be analysed with Cox mixed-effects model. Secondary endpoints include ventilator-free and vasopressor-free days up to day 30. A total of 710 patients will be included in the trial.Ethics and dissemination The trial was approved by the responsible ethics committee and by Germany’s Federal Institute for Drugs and Medical Devices. The clinical trial application was submitted under the new Clinical Trials Regulation through CTIS (The Clinical Trials Information System). In this process, only one ethics committee, whose name is unknown to the applicant, and Germany’s Federal Institute for Drugs and Medical Devices are involved throughout the entire approval process. Results will be published in a journal indexed in MEDLINE and CTIS. With publication, de-identified, individual participant data will be made available to researchers.Trial registration number NCT06134492.

Introduction Sepsis remains the major cause of death among hospitalised patients in intensive care. While targeting sepsis-causing pathogens with source control or antimicrobials has had a dramatic impact on morbidity and mortality of sepsis patients, this strategy remains insufficient for about one-third of the affected individuals who succumb. Pharmacological targeting of mechanisms that reduce sepsis-defining organ dysfunction may be beneficial. When given at low doses, the anthracycline epirubicin promotes tissue damage control and lessens the severity of sepsis independently of the host–pathogen load by conferring disease tolerance to infection. Since epirubicin at higher doses can be myelotoxic, a first dose–response trial is necessary to assess the potential harm of this drug in this new indication.Methods and analysis Epirubicin for the Treatment of Sepsis and Septic Shock-1 is a randomised, double-blind, placebo-controlled phase 2 dose-escalation phase IIa clinical trial to assess the safety of epirubicin as an adjunctive in patients with sepsis. The primary endpoint is the 14-day myelotoxicity. Secondary and explorative outcomes include 30-day and 90-day mortality, organ dysfunction, pharmacokinetic/pharmacodynamic (PK/PD) and cytokine release. Patients will be randomised in three consecutive phases. For each study phase, patients are randomised to one of the two study arms (epirubicin or placebo) in a 4:1 ratio. Approximately 45 patients will be recruited. Patients in the epirubicin group will receive a single dose of epirubicin (3.75, 7.5 or 15 mg/m2 depending on the study phase. After each study phase, a data and safety monitoring board will recommend continuation or premature stopping of the trial. The primary analyses for each dose level will report the proportion of myelotoxicity together with a 95% CI. A potential dose-toxicity association will be analysed using a logistic regression model with dose as a covariate. All further analyses will be descriptive.Ethics and dissemination The protocol is approved by the German Federal Institute for Drugs and Medical Devices. The results will be submitted for publication in peer-reviewed journals.Trial registration number NCT05033808.

Terrestrial ecosystems such as coniferous forests in Central Europe are experiencing changes in health status following extreme droughts compounding with severe heat waves. The increasing temporal resolution and spatial coverage of earth observation data offer new opportunities to assess these dynamics. Dense time-series of optical satellite data allow for computing Dynamic Habitat Indices (DHIs), which have been predominantly used in biodiversity studies. However, DHIs cover three aspects of vegetation changes that could be affected by drought: annual productivity, minimum cover, and seasonality. Here, we evaluate the health status of coniferous forests in the federal state of Hesse in Germany over the period 2017–2020 including the severe drought year of 2018 using DHIs based on the Normalized Difference Vegetation Index (NDVI) for drought assessment. To identify the most important variables affecting coniferous forest die-off, a series of environmental variables together with the three DHIs components were used in a logistic regression (LR) model. Each DHI component changed significantly across non-damaged and damaged sites in all years (p-value 0.05). When comparing 2017 to 2019, DHI-based annual productivity decreased and seasonality increased. Most importantly, none of the DHI components had reached pre-drought conditions, which likely indicates a change in ecosystem functioning. We also identified spatially explicit areas highly affected by drought. The LR model revealed that in addition to common environmental parameters related to temperature, precipitation, and elevation, DHI components were the most important factors explaining the health status. Our analysis demonstrates the potential of DHIs to capture the effect of drought events on Central European coniferous forest ecosystems. Since the spaceborne data are available at the global level, this approach can be applied to track the dynamics of ecosystem conditions in other regions, at larger spatial scales, and for other Land Use/Land Cover types.

Background:. There is a trend toward matching in a different region than previous training for the independent plastic surgery match cycles from 2019 to 2021, which differs from the trend to match within the same region for integrated plastic surgery programs. Notably, residency interviews transitioned from in-person to virtual in 2020 due to the coronavirus pandemic. Therefore, we compared in-person versus virtual interview match trends from 2019 to 2023. Methods:. Zip codes and regions of each successfully matched plastic surgery applicant’s medical school, residency, and plastic surgery program were gathered from publicly available data for the 2019 and 2020 in-person interview cycles and 2021, 2022, and 2023 virtual interview cycles. Results:. Although regions did not differ significantly in the proportions of positions each year (P = 0.85), there was a trend toward fewer positions in each region from 2019 to 2022. Overall, applicants were more likely to match in a different region as their medical school or residency during virtual compared with in-person interviews (P = 0.002 and P = 0.04). Applicants matched to programs further from their medical school zip code in virtual interview years (P = 0.02). There was no significant difference in distance between surgical residencies and plastic surgery residencies between the two time periods (P = 0.51). Conclusions:. Trends toward matching into a different region than prior training after the switch to virtual interviews could be attributed to applicant accessibility to interview broadly. However, this could also be due to the decreased number of independent residency positions over the years, requiring applicants to move regions and travel further from where they began their training.

As severe acute respiratory coronavirus 2 (SARS-CoV-2) variants continue to emerge, it is important to characterize immune responses against variants which can inform on protection efficacies following booster vaccination. In this study, neutralizing breadth and antigen-specific CD8+ T cell responses were analyzed in both infection-naïve and infection-experienced individuals following administration of a booster bivalent Wuhan-Hu-1+BA.4/5 Comirnaty® mRNA vaccine. Significantly higher neutralizing titers were found after this vaccination compared to the pre-third booster vaccination time point. Further, neutralizing breadth to omicron variants, including BA.1, BA.2, BA.5, BQ.1 and XBB.1, was found to be boosted following bivalent vaccination. SARS-CoV-2-specific CD8+ T cells were identified, but with no evidence that frequencies were increased following booster vaccinations. Spike protein-specific CD8+ T cells were the only responses detected after vaccination and non-spike-specific CD8+ T cells were only detected after infection. Both spike-specific and non-spike-specific CD8+ T cells were found at much lower frequencies than CD8+ T cells specific to cytomegalovirus (CMV), Epstein-Barr virus (EBV) and influenza (Flu). Taken together, these results show that the bivalent Wuhan-Hu-1+BA.4/5 Comirnaty® mRNA vaccine boosted the breadth of neutralization to newer SARS-CoV-2 variants and that vaccination is able to induce spike protein-specific CD8+ T cell responses, which are maintained longitudinally.

BackgroundCoronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis.MethodsWe analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression.ResultsIn 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8-6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome.ConclusionsMortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis.

BackgroundThe criteria for PD-MCI allow the use of global cognitive tests. Their predictive value for conversion from PD-MCI to PDD, especially compared to comprehensive neuropsychological assessment, is unknown.MethodsThe MDS PD-MCI Study Group combined four datasets containing global cognitive tests as well as a comprehensive neuropsychological assessment to define PD-MCI (n = 467). Risk for developing PDD was examined using a Cox model. Global cognitive tests were compared to neuropsychological test batteries (Level I&II) in determining risk for PDD.ResultsPD-MCI based on a global cognitive test (MMSE or MoCA) increases the hazard for developing PDD (respectively HR = 2.57, P = 0.001; HR = 4.14, P =

Lyme disease, which is caused by several species of Borrelia burgdorferi sensu lato complex (Lyme borreliae), is the most common vectorborne disease in the Northern Hemisphere. The US Centers for [...]