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ObjectiveTo characterize sequential patterns of regional neuropathology and clinical symptoms in a well-characterized cohort of 21 patients with autopsy-confirmed Pick disease.MethodsDetailed neuropathological examination using 70μm and traditional 6μm sections was performed using thioflavin-S staining and immunohistochemistry for phosphorylated tau, 3R and 4R tau isoforms, ubiquitin, and C-terminally truncated tau. Patterns of regional tau deposition were correlated with clinical data. In a subset of cases (n = 5), converging evidence was obtained using antemortem neuroimaging measures of gray and white matter integrity.ResultsFour sequential patterns of pathological tau deposition were identified starting in frontotemporal limbic/paralimbic and neocortical regions (phase I). Sequential involvement was seen in subcortical structures, including basal ganglia, locus coeruleus, and raphe nuclei (phase II), followed by primary motor cortex and precerebellar nuclei (phase III) and finally visual cortex in the most severe (phase IV) cases. Behavioral variant frontotemporal dementia was the predominant clinical phenotype (18 of 21), but all patients eventually developed a social comportment disorder. Pathological tau phases reflected the evolution of clinical symptoms and degeneration on serial antemortem neuroimaging, directly correlated with disease duration and inversely correlated with brain weight at autopsy. The majority of neuronal and glial tau inclusions were 3R tau-positive and 4R tau-negative in sporadic cases. There was a relative abundance of mature tau pathology markers in frontotemporal limbic/paralimbic regions compared to neocortical regions.InterpretationPick disease tau neuropathology may originate in limbic/paralimbic cortices. The patterns of tau pathology observed here provide novel insights into the natural history and biology of tau-mediated neurodegeneration.

Abstract Background Societies strive for fast-delivered, evidence-based and need-oriented depression treatment within budget constraints. To explore potential improvements, selective contracts can be implemented. Here, we evaluate if the German collaborative psychiatry-neurology-psychotherapy contract (PNP), which extends the gatekeeping-based general practitioner (GP) program, improved guideline adherence or need-oriented and timely access to psychotherapy compared to usual care (UC). Methods We conducted a retrospective observational cohort study based on health insurance claims data. After we identified patients with depression who were on sick leave due to a mental disorder in 2015, we applied entropy balancing to adjust for selection effects and employed chi-squared tests to compare guideline adherence of the received treatment between PNP, the GP program and UC. Subsequently, we applied an extended cox regression to assess need-orientation by comparing the relationship between accumulated sick leave days and waiting times for psychotherapy across health plans. Results N = 23,245 patients were included. Regarding guideline adherence, we found no significant differences for most severity subgroups; except that patients with a first moderate depressive episode received antidepressants or psychotherapy more often in UC. Regarding need-orientation, we observed that the effect of each additional month of sick leave on the likelihood of starting psychotherapy was increased by 6% in PNP compared to UC. Irrespective of the health plan, we found that within the first 12 months only between 24.3 and 39.7% (depending on depression severity) received at least 10 psychotherapy sessions or adequate pharmacotherapy. Conclusions The PNP contract strengthens the relationship between sick leave days and the delay until the beginning of psychotherapy, which suggests improvements in terms of need-oriented access to care. However, we found no indication for increased guideline adherence and – independent of the health plan – a gap in sufficient utilization of adequate treatment options.

Abstract Background Depression is associated with major patient burden. Its treatment requires complex and collaborative approaches. A stepped care model based on the German National Clinical Practice Guideline “Unipolar Depression” has been shown to be effective. In this study we assess the cost-effectiveness of this guideline based stepped care model versus treatment as usual in depression. Methods This prospective cluster-randomized controlled trial included 737 depressive adult patients. Primary care practices were randomized to an intervention (IG) or a control group (CG). The intervention consisted of a four-level stepped care model. The CG received treatment as usual. A cost-utility analysis from the societal perspective with a time horizon of 12 months was performed. We used quality-adjusted life years (QALY) based on the EQ-5D-3L as effect measure. Resource utilization was assessed by patient questionnaires. Missing values were imputed by ‘multiple imputation using chained equations’ based on predictive mean matching. We calculated adjusted group differences in costs and effects as well as incremental cost-effectiveness ratios. To describe the statistical and decision uncertainty cost-effectiveness acceptability curves were constructed based on net-benefit regressions with bootstrapped standard errors (1000 replications). The complete sample and subgroups based on depression severity were considered. Results We found no statically significant differences in costs and effects between IG and CG. The incremental total societal costs (+€5016; 95%-CI: [−€259;€10,290) and effects (+ 0.008 QALY; 95%-CI: [− 0.030; 0.046]) were higher in the IG in comparison to the CG. Significantly higher costs were found in the IG for outpatient physician services and psychiatrist services in comparison to the CG. Significantly higher total costs and productivity losses in the IG in comparison to the CG were found in the group with severe depression. Incremental cost-effectiveness ratios for the IG in comparison to the CG were unfavourable (complete sample: €627.000/QALY gained; mild depression: dominated; moderately severe depression: €645.154/QALY gained; severe depression: €2082,714/QALY gained) and the probability of cost-effectiveness of the intervention was low, except for the group with moderate depression (ICER: dominance; 70% for willingness-to-pay threshold of €50,000/QALY gained). Conclusions We found no evidence for cost-effectiveness of the intervention in comparison to treatment as usual. Trial registration NCT, NCT01731717 . Registered 22 November 2012 - Retrospectively registered.

Alcohol's impairment of both hepatic lipid metabolism and insulin resistance (IR) are key drivers of alcoholic steatosis, the initial stage of alcoholic liver disease (ALD). Pharmacologic reduction of lipotoxic ceramide prevents alcoholic steatosis and glucose intolerance in mice, but potential off-target effects limit its strategic utility. Here, we employed a hepatic-specific acid ceramidase (ASAH) overexpression model to reduce hepatic ceramides in a Lieber-DeCarli model of experimental alcoholic steatosis. We examined effects of alcohol on hepatic lipid metabolism, body composition, energy homeostasis, and insulin sensitivity as measured by hyperinsulinemic-euglycemic clamp. Our results demonstrate that hepatic ceramide reduction ameliorates the effects of alcohol on hepatic lipid droplet (LD) accumulation by promoting VLDL secretion and lipophagy, the latter of which involves ceramide cross-talk between the lysosomal and LD compartments. We additionally demonstrate that hepatic ceramide reduction prevents alcohol's inhibition of hepatic insulin signaling. These effects on the liver are associated with a reduction in oxidative stress markers and are relevant to humans, as we observe peri- LD ASAH expression in human ALD. Together, our results suggest a potential role for hepatic ceramide inhibition in preventing ALD.

Consuming high amounts of fast food can lead to an excessive intake of energy and subsequently promote obesity. Obesity increases a person’s risk for diabetes and cardiovascular diseases. The second wave of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS Wave 2, 2014–2017) included the Eating study as a KiGGS Module (EsKiMo II, 2015–2017) which assessed the self-reported dietary habits of children and adolescents in Germany. The analysis of the data permits an overview of the fast food consumption of 12- to 17-year-olds (n=1,353). Girls consume 57.5 grams and boys 86.3 grams of fast food per day on average (around 400 grams and 600 grams per week, respectively). Pizza is the most consumed fast food product, followed by filled pita and sausage/meat products such as curry sausage. Adolescent girls on average get 6.5% and boys 7.8% of total daily energy intake from fast food. 23% of 12- to 17-year-olds get at least 10% of their daily energy intake from fast food (high consumers). Significant differences between the proportion of high consumers exist regarding sex, age, socioeconomic status, community size, type of school and media consumption. Compared to EsKiMo I (2006), girls’ daily energy intake from fast food has remained nearly constant, whereas that of boys has dropped substantially. From a nutrition physiology perspective, the aim should be to further reduce fast food consumption.

Data from the second Eating study as a KiGGS module (EsKiMo II, 2015–2017), are used to determine the contribution of food produced by organic farming (organic food) to the diet of children aged between six and eleven years (n=1,190) in Germany. Dietary intake was assessed by food records during a total of four days. Information on the proportion of organic food intake relative to daily food intake was used to differentiate between three groups: children who did not consume organic food; children whose diet contains 8.0% or less of organic food; and children whose diet comprises more than 8.0% of organic food. The 8.0% threshold represents the mean proportion of organic food eaten by children whose diet includes any amount of organic produce. In total, 63.2% of children eat organic food. The diet of 43.0% of children contains 8.0% or less of organic food, with the diet of 20.2% comprising more than 8.0% of organic food. Vegetables and fruit are among the most commonly consumed organic products. While consumption frequency of organic food does not differ by sex or age, consumption frequency increases with higher socioeconomic status. The large proportion of children (63.2%) who eat organic food suggests that health, environmental and ethical motives play a role in the food choices made by families with children.

The development of a proof-of-concept point-of-care (PoC) device for the determination of oral anticoagulants determination is presented. Acenocoumarol (ACL) is prescribed to prevent certain cardiovascular diseases related to the prevention of deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke. Oral anticoagualant treatment (OAT) represents a population of 2% under treatment which has expenditures about $ 144 million in 2011. The main drawback for OAT is the associated narrow therapeutic window and the unpredictable dose-response relationship, which is one of the main causes for visiting the emergency room at the hospitals. In a previous work, family antibodies were produced for the simultaneous detection of ACL and warfarin (W) depending on the area of application. It was developed in different formats, indirect and direct, either with similar detectabilities and both assays quantifying the oral anticoagulants with high accuracy and reproducibility. We present the implementation of the already developed immunochemical method to a point-of-care (PoC) device to assist on the patient compliance assessment programs. In order to achieve this goal, a first development was performed implementing ACL ELISA assay into a microarray format with fluorescent read-out. The assay was successfully implemented achieving a LOD of 1.23 nM of ACL directly measured in human plasma. Then, a fully integrated microfluidic system is developed which incorporates the specific immunoreagents for the detection of ACL. The immunoreagents were attached onto the glass slide in a microarray format. The system is automatic, rapid, sensitive, and disposable that could help clinicians monitor patients under OAT. According to the fluorescent label of the ACL binding, the chip can be easily read with a scanner. The microfluidic system performed good according to the robust and reproducible signals, and subsequently yielded an accurate result.

Anxiety disorders are among the most common mental health problems in primary care. The PARADIES (Patient Activation foR Anxiety DIsordErS) intervention combined elements of cognitive behavioural therapy with case management and has demonstrated efficacy. Our aim was to explore patient characteristics, which may influence the course of anxiety symptoms over a 12 months period. Multiple linear regression was used to quantify associations of baseline characteristics (demographics, clinical parameters, medication use) with changes in anxiety symptoms as measured by the Beck anxiety inventory. Treatment modalities (e.g. adherence to appointment schedules) were considered as confounders. We examined univariate associations between dependent and independent variables before considering all independent variables in a multivariate final model. To find the best model to explain BAI score changes, we performed step-wise selection of independent variables based on Akaike information criteria. We tested for interaction terms between treatment allocation (intervention vs control) and independent variables using the multivariate model. We repeated these analyses in control vs intervention groups separately. From the original trial (N = 419), 236 patients (56.3%) were included. In the multivariate model, receiving the intervention (p

Despite major progress in the design of power transformers, the Achilles’ heel remains the insulation system, which is affected by various parameters including moisture, heat, and vibrations. These important machines require extreme reliability to guarantee electricity distribution to end users. In this contribution, a fiber optic sensor (FOS), consisting of a Fabry–Perot cavity made up of two identical fiber Bragg gratings (FBGs), is proposed, to monitor the temperature and vibration of power transformer windings. A phase shifted gratings recoated sensor, with multilayers of polyimide films, is used to monitor the moisture content in oil. The feasibility is investigated using an experimental laboratory transformer model, especially fabricated for this application. The moisture contents are well correlated with those measured by a Karl Fisher titrator, while the values of temperature compare well with those recorded from thermocouples. It is also shown that the sensors can be used to concurrently detect vibration, as assessed by sensitivity to the loading current. The possibility of dynamically measuring humidity, vibrations, and temperatures right next to the winding, appears to be a new insight that was previously unavailable. This approach, with its triple ability, can help to reduce the required number of sensors and therefore simplify the wiring layout.

With the growth of the world’s population and faster-developing industries, larger amounts of electric energy are needed [...]

Digitalisierung impliziert für die Wissenschaft insbesondere die digitale Verfüg- und Austauschbarkeit des „Rohstoffs“ Forschungsdaten. Dies setzt die Schaffung und Vernetzung von rechtssicheren Datenräumen voraus. Die Ausgestaltung der Bedingungen, unter denen dort Forschungsdaten geteilt und nachgenutzt werden dürfen, liegt dabei in der Entscheidungshoheit der Forschenden. Vehikel zur Ausübung dieser Selbstbestimmung ist die Vergabe von Lizenzen. Um dazu eine Hilfestellung zu bieten, analysiert der Beitrag vorhandene Lizenzempfehlungen und prüft die Eignung verschiedener Lizenzmodelle, bevor abschließend eine eigene, differenzierte Empfehlung ausgesprochen wird.

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Tina Mallon,1 Marion Eisele,1 Hans-Helmut König,2 Christian Brettschneider,2 Susanne Röhr,3 Alexander Pabst,3 Siegfried Weyerer,4 Jochen Werle,4 Edelgard Mösch,5 Dagmar Weeg,5 Angela Fuchs,6 Michael Pentzek,6 Kathrin Heser,7 Birgitt Wiese,8 Luca Kleineidam,9 Michael Wagner,9 Steffi Riedel-Heller,3 Wolfgang Maier,7,9 Martin Scherer1 1Department of Primary Medical Care, Center for Psychosocial Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 2Department of Health Economics and Health Services Research, Hamburg Center for Health Economics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 3Institute of Social Medicine, Occupational Health and Public Health (ISAP), University of Leipzig, Leipzig, Germany; 4Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany; 5Department of Psychiatry, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany; 6Institute of General Practice, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany; 7Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany; 8Work Group Medical Statistics and IT-Infrastructure, Institute for General Practice, Hannover Medical School, Hannover, Germany; 9DZNE, German Center for Neurodegenerative Diseases, Bonn, GermanyCorrespondence: Tina MallonDepartment of Primary Medical Care, Center for Psychosocial Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyTel +49-40-741057164Fax +49-40-741053681Email t.mallon@uke.dePurpose: Dealing with the high prevalence of pain among the oldest-old (+75) is becoming a major health issue. Therefore, the aim of the study was to uncover health-related lifestyle behaviors (HLB) and age-related comorbidities which may predict, influence and prevent pain in old age.Patients and methods: In this longitudinal cohort study, data were obtained initially from 3.327 individuals aged 75+ from over 138 general practitioners (GP) during structured clinical interviews in 2003. Nine follow-ups (FU) were assessed until 2017. Available data from 736 individuals scoring in FU3 and FU7 were included in this analysis. Data were assembled in an ambulatory setting at participant’s homes. Associations were tested using a linear regression model (model 1) and ordered logistic regression model (model 2).Results: Statistical analyses revealed increased likelihood to experience pain for participants with comorbidities such as peripheral arterial disease (PAD) (coef. 13.51, P>t = 0.00) or chronic back pain (CBP) (coef. 6.64, P>t = 0.003) or higher body mass index (BMI) (coef. 0.57, P>t = 0.015) and, female gender (coef. 6.00, SE 3.0, t = 2.02, P>t = 0.044). Participants with medium education and former smokers showed significantly lower pain rating (coef. −5.05, P>t = 0.026; coef. −5.27, P>t = 0.026). Suffering from chronic back pain (OR = 2.03), osteoarthritis (OR = 1.49) or depressive symptoms (OR = 1.10) raised the odds to experience impairments in daily living due to pain. Physical activity showed no significant results.Conclusion: Chronic conditions such as PAD, or CBP, female gender and higher BMI may increase the risk of experiencing more pain while successful smoking cessation can lower pain ratings at old age. Early and consistent support through GPs should be given to older patients in order to prevent pain at old age.Keywords: oldest-old, health-related aspects, pain prevention, longitudinal cohort study, chronic conditions

Abstract Background Panic disorder is a mental disorder of high prevalence, which frequently co-occurs with agoraphobia. There is a lack of studies measuring excess costs of panic disorder patients with and without agoraphobia. We compared costs of panic disorder patients with or without agoraphobia with costs of the anxiety-free population in Germany. Methods Primary data from a cluster-randomized trial of adults suffering from panic disorder (n = 419) and from a representative survey of the German general population (N = 5005) were collected between 2012 and 2014. Missing data from the cluster-randomized trial were first imputed by multiple imputation using chained equations and subsequently balanced with the data from the survey by Entropy Balancing. The societal perspective was chosen. Excess costs were calculated by generalized linear models and two-part-models. Results Entropy Balancing led to an exact match between the groups. We found 6-month total excess costs of 3220€ (95% CI 1917€–4522€) for panic disorder patients without agoraphobia and of 3943€ (95% CI 2950€–4936€) for patient with agoraphobia. Panic disorder patients with or without agoraphobia had significantly higher costs for psychotherapy, general practitioners, general hospital stays and informal care Indirect costs accounted for approximately 60% of the total excess costs. Conclusions Panic disorder with or without agoraphobia is associated with significant excess costs. Agoraphobia changes the pattern of resource utilization. Especially indirect costs are relevant. Agoraphobia influences resource utilization in the inpatient sector. Trial registration ISRCTN64669297

Abstract Background Approximately 90% of German surface waters do not meet the objectives of the European Water Framework Directive (EU-WFD). This is primarily due to deficits in water body structure and biological quality components, which in turn are negatively affected by chemical pollution. In this context, hydromorphological restoration measures have often been conducted to improve habitat and species diversity and, therefore, the ecological status of water bodies. However, habitat improvement is not necessarily accompanied by biota enhancement and thus by the improvement of the ecological status of rivers. To prioritize water management measures, decision criteria for the water management practice are necessary, which enable the prognosis, whether chemical pollution and its resulting effects or other factors, such as structural deficits of the water bodies, are the main cause for the failure to meet the objective of a good ecological status. Results To address this need, we applied the freshwater mudsnail Potamopyrgus antipodarum and the amphipod Gammarus fossarum in active monitoring campaigns and in laboratory experiments with combined water/sediment samples and analyzed water and sediment samples with in vitro assays quarterly over the course of 1 year to provide evidence and guideline to assess if chemical contamination is a relevant stress factor for the aquatic biodiversity in rivers of the Nidda catchment (Hessen, Germany). On the basis of these results, an ecotoxicological, WFD–compliant assessment system was developed which, in comparison with the ecological status classes of the EU-WFD, permits the identification of the probable causes for the failure to meet the objectives of the EU-WFD. From these findings, recommendations for action were derived for the implementation of priority measures in water management practice. For the rivers Nidda, Usa, and Horloff, we identified a need for action to improve water and sediment quality at all investigated sampling sites except for the reference sites in the headwaters. The ecotoxicological assessment system also highlighted that hydromorphological restoration measures on their own will not lead to a good ecological status of rivers, as long as water and sediment quality are deficient. Conclusion Hydromorphological restoration measures should be performed in conjunction with measures to reduce chemical contamination to achieve a good ecological status of the rivers Nidda, Usa, and Horloff.

Reported levels of amyloid-beta and tau in human cerebrospinal fluid (CSF) were evaluated to discover if these biochemical markers can predict the transition from Mild Cognitive Impairment (MCI) to Alzheimer’s disease (AD). A systematic review of the literature in PubMed and Web of Science (April 2021) was performed by a single researcher to identify studies reporting immunologically-based (xMAP or ELISA) measures of CSF analytes Aβ(1-42) and/or P-tau and/or T-tau in clinical studies with at least two timepoints and a statement of diagnostic criteria. Of 1137 screened publications, 22 met the inclusion criteria for CSF Aβ(1-42) measures, 20 studies included T-tau, and 17 included P-tau. Six meta-analyses were conducted to compare the analytes for healthy controls (HC) versus progressive MCI (MCI_AD) and for non-progressive MCI (Stable_MCI) versus MCI_AD; effect sizes were determined using random effects models. The heterogeneity of effect sizes across studies was confirmed with very high significance (p < 0.0001) for all meta-analyses except HC versus MCI_AD T-tau (p < 0.05) and P-tau (non-significant). Standard mean difference (SMD) was highly significant (p < 0.0001) for all comparisons (Stable_MCI versus MCI_AD: SMD [95%-CI] Aβ(1-42) = 1.19 [0.96,1.42]; T-tau = −1.03 [−1.24,−0.82]; P-tau = −1.03 [−1.47,−0.59]; HC versus MCI_AD: SMD Aβ(1-42) = 1.73 [1.39,2.07]; T-tau = −1.13 [−1.33,−0.93]; P-tau = −1.10 [−1.23,−0.96]). The follow-up interval in longitudinal evaluations was a critical factor in clinical study design, and the Aβ(1–42)/P-tau ratio most robustly differentiated progressive from non-progressive MCI. The value of amyloid-beta and tau as markers of patient outcome are supported by these findings.

The use of immunotherapies for the treatment of brain tumors is a topic that has garnered considerable excitement in recent years. Discoveries such as the presence of a glymphatic system and immune surveillance in the central nervous system (CNS) have shattered the theory of immune privilege and opened up the possibility of treating CNS malignancies with immunotherapies. However, despite many immunotherapy clinical trials aimed at treating glioblastoma (GBM), very few have demonstrated a significant survival benefit. Several factors for this have been identified, one of which is that GBMs are immunologically “cold,” implying that the cancer does not induce a strong T cell response. It is postulated that this is why clinical trials using an immune checkpoint inhibitor alone have not demonstrated efficacy. While it is well established that anti-cancer T cell responses can be facilitated by the presentation of tumor-specific antigens to the immune system, treatment-related death of GBM cells and subsequent release of molecules have not been shown to be sufficient to evoke an anti-tumor immune response effective enough to have a significant impact. To overcome this limitation, vaccines can be used to introduce exogenous antigens at higher concentrations to the immune system to induce strong tumor antigen-specific T cell responses. In this review, we will describe vaccination strategies that are under investigation to treat GBM; categorizing them based on their target antigens, form of antigens, vehicles used, and pairing with specific adjuvants. We will review the concept of vaccine therapy in combination with immune checkpoint inhibitors, as it is hypothesized that this approach may be more effective in overcoming the immunosuppressive milieu of GBM. Clinical trial design and the need for incorporating robust immune monitoring into future studies will also be discussed here. We believe that the integration of evolving technologies of vaccine development, delivery, and immune monitoring will further enhance the role of these therapies and will likely remain an important area of investigation for future treatment strategies for GBM patients.

Objectives The objectives of this study were to estimate the direct and indirect excess costs of type 2 diabetes mellitus (T2D) using data representative for the German adult population and to investigate the association of sociodemographic and clinical determinants with these excess costs.Setting We calculated mean annual costs for individuals with T2D and a control group without diabetes, using data on healthcare utilisation and productivity losses from the cross-sectional German Health Interview and Examination Survey for Adults. We adjusted for group differences using entropy balancing and estimated excess costs for total, direct, indirect costs and additional cost categories using generalised linear models. We performed subgroup analyses to investigate the association of sociodemographic (age, sex and education) and clinical determinants (diabetes duration, glycaemic index and complications) with excess costs.Participants The final study sample included n=325 individuals with T2D and n=4490 individuals without diabetes in the age between 18 and 79 years.Results Total excess costs amounted to €927, of which €719 were attributable to direct and €209 to indirect excess costs. Total costs were significantly increased by 28% for T2D compared with controls. Group differences in direct, outpatient and medication costs were statistically significant. Medication costs were 88% higher for T2D and had the highest share in direct excess costs. With respect to specific determinants, direct excess costs ranged from €203 for 4–10 years diabetes duration to €1405 for diabetes complications. Indirect excess costs ranged from €−544 for >10 years diabetes duration to €995 for high education.Conclusions T2D was associated with high costs, mainly due to direct costs. As pointed out by our results, diabetes complications and comorbidities have a large impact on the costs, leaving medication costs as main contributor of T2D excess costs.

Lack of adequate sanitation and pest control, and poor housing conditions that prevail in much of both rural and urban South Africa, cause rodent populations to thrive, promoting contact with humans, which results in increased risk of zoonotic disease transmission. This study focused on bacterial pathogens involved in potential zoonoses present in three commensal and invasive Rattus spp., namely Rattus norvegicus, R. rattus, and R. tanezumi, from rural and urban South Africa. Bacterial prevalence and diversity was determined through amplification and sequencing of the mitochondrial 16S gene region, using four primer sets: two that have a broad bacterial species recognition range, and two genus-specific sets that target the genera Streptococcus and Streptobacillus. An overall bacterial prevalence of 32% (n = 84) in kidney samples was obtained using the 16S universal primer sets. Subsequent sequence analyses found bacterial prevalence per host species to be 41% for R. norvegicus, 42% for R. rattus, and 8% for R. tanezumi, with representatives of diverse bacterial taxa such as Clostridium sordelli (toxic shock syndrome), Bacillus cereus (diarrhoeal disease), and Enterococcus faecalis (nosocomial infections) being characterised. The primer set targeting Streptobacillus moniliformis was used to determine the prevalence of this zoonotically-important bacterial taxon, which is transmissible via a bite from Rattus to humans, whilst Streptococcus-specific primers were used to assess environmental shedding of this agent via the urinary route. The results highlight the public health implications especially for immune-compromised individuals, as these rodent-borne pathogens can cause opportunistic infections that in such individuals are not readily diagnosed or treated.

Forschungsdatenmanagement (FDM) ist für eine digital arbeitende Wissenschaft unerlässlich. Wissenschaft und Infrastruktureinrichtungen haben darauf – unterstützt durch Förderprogramme von Ländern, Bund und EU – mit dem Aufbau neuer Dienste und Strukturen reagiert. Eine zentrale Heraus-forderung ist es, die verschiedenen Strukturen, Initiativen und Projekte dergestalt aufeinander abzustimmen, dass Doppelarbeiten vermieden und Synergien geschaffen werden. Der Beitrag zeigt an der baden-württembergischen FDM-Landesinitiative bw2FDM beispielhaft auf, wie die Vernetzung verschiedener Akteure am Standort, auf Landes- und auf überregionaler Ebene gelingen kann.

Unabhängig von der einzelnen Fachdisziplin besteht in einer stark vernetzten und hochgradig kooperativen Wissenschaftslandschaft das Ziel, Dienste für das Forschungsdatenmanagement zu föderieren oder zumindest eng miteinander abzustimmen. Von zentraler Bedeutung sind dabei persistente Identifikatoren für Forschende. Wegen der hohen Fluktuation innerhalb dieser Personengruppe wäre eine Einigung aller Teilnehmerinnen und Teilnehmer am Wissenschaftsbetrieb auf ein einheitliches, international anerkanntes und institutionenübergreifendes System wie die ORCID eine erhebliche Erleichterung, da ein Wechsel zwischen Einrichtungen nicht länger Änderungen in der Datenbasis erforderlich machen würde. Eine vergleichbare Herausforderung besteht in der eindeutigen Bezeichnung einer Einrichtung. Dieses Problem adressiert das Research Organization Registry (ROR). Ein Identifier sollte stabil und eindeutig für Personen und Einrichtungen sein. Dieser Erfahrungsbericht beschreibt die Überlegungen und Schritte zur Standardisierung im Umgang mit langfristigen Personen- und Institutionen-Identifiern, die der Arbeitskreis Forschungsdatenmanagement (AK FDM) in Baden-Württemberg erarbeitet hat. In einem ersten Schritt hat der AK FDM sich dem Memorandum of Understanding (MoU) von DINI angeschlossen und eine Empfehlung sowohl für ORCID als auch ROR ausgesprochen. Insbesondere wird empfohlen in Forschungsinformationssystemen, Repositorien und im Forschungsdatenmanagement Personen über die ORCID ID, Organisationen über die ROR ID[1] und Repositorien über re3data[1] auszuweisen. Darüber hinaus wird auf die ORCID ID in Informations- und Lehrveranstaltungen zum FDM verstärkt hingewiesen. Außerdem werden Überlegungen zur Aufnahme in die lokalen Identity-Managementsysteme und eine Bereitstellung als Attribut in der Baden-Württemberg-weiten IDM-Föderation vorangetrieben. Letzteres soll eine Grundlage schaffen aus der sich nicht nur FDM-spezifische Dienste bedienen können, um die ORCID ID bereits automatisch in Workflows zu übernehmen und mit Daten der Nutzenden zu verknüpfen.

Prediction of subject age from brain anatomical MRI has the potential to provide a sensitive summary of brain changes, indicative of different neurodegenerative diseases. However, existing studies typically neglect the uncertainty of these predictions. In this work we take into account this uncertainty by applying methods of functional data analysis. We propose a penalised functional quantile regression model of age on brain structure with cognitively normal (CN) subjects in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), and use it to predict brain age in Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD) subjects. Unlike the machine learning approaches available in the literature of brain age prediction, which provide only point predictions, the outcome of our model is a prediction interval for each subject.

ObjectivesSocial isolation is increasing in aging societies and several studies have shown a relation with worse cognition in old age. However, less is known about the association in the oldest-old (85+); the group that is at highest risk for both social isolation and dementia.MethodsAnalyses were based on follow-up 5 to 9 of the longitudinal German study on aging, cognition, and dementia in primary care patients (AgeCoDe) and the study on needs, health service use, costs, and health-related quality of life in a large sample of oldest-old primary care patients (AgeQualiDe), a multi-center population-based prospective cohort study. Measurements included the Lubben Social Network Scale (LSNS-6), with a score below 12 indicating social isolation, as well as the Mini-Mental Status Examination (MMSE) as an indicator of cognitive function.ResultsDementia-free study participants (n = 942) were M = 86.4 (SD = 3.0) years old at observation onset, 68.2% were women. One third (32.3%) of them were socially isolated. Adjusted linear hybrid mixed effects models revealed significantly lower cognitive function in individuals with smaller social networks (β = 0.5, 95% CI = 0.3–0.7, p < .001). Moreover, changes in an individual’s social network size were significantly associated with cognitive changes over time (β = 0.2, 95% CI = 0.1–0.4, p = .003), indicating worse cognitive function with shrinking social networks.ConclusionSocial isolation is highly prevalent among oldest-old individuals, being a risk factor for decreases in cognitive function. Consequently, it is important to maintain a socially active lifestyle into very old age. Likewise, this calls for effective ways to prevent social isolation.

Abstract Background Suicidal ideation is common in patients suffering from panic disorder. The present study investigated rates of suicidal ideation and risk factors for suicidal ideation in a sample of primary care patients suffering from panic disorder with or without agoraphobia. Methods A total of N = 296 patients [n = 215 (72.6%) women; age: M = 43.99, SD = 13.44] were investigated. Anxiety severity, anxiety symptoms, avoidance behavior, comorbid depression diagnosis, severity of depression, age, sex, employment status, living situation and frequency of visits at the general practitioner were considered as risk factors of suicidal ideation. Results Suicidal ideation was experienced by 25% of the respondents. In a logistic regression analysis, depression diagnosis and depression severity emerged as significant risk factors for suicidal ideation. Anxiety measures were not associated with suicidal ideation. Conclusion Suicidal ideation is common in primary care patients suffering from panic disorder with or without agoraphobia. Individuals with greater burden of mental illness in terms of mood disorder comorbidity and depressive symptomatology are especially likely to suffer from suicidal ideation.

Abstract Background Traumatic events like critical illness and intensive care are threats to life and bodily integrity and pose a risk factor for posttraumatic stress disorder (PTSD). PTSD affects the quality of life and morbidity and may increase health-care costs. Limited access to specialist care results in PTSD patients being treated in primary care settings. Narrative exposure therapy (NET) is based on the principles of cognitive behavioral therapy and has shown positive effects when delivered by health-care professionals other than psychologists. The primary aims of the PICTURE trial (from “PTSD after ICU survival”) are to investigate the effectiveness and applicability of NET adapted for primary care with case management in adults diagnosed with PTSD after intensive care. Methods/design This is an investigator-initiated, multi-center, primary care-based, randomized controlled two-arm parallel group, observer-blinded superiority trial conducted throughout Germany. In total, 340 adult patients with a total score of at least 20 points on the posttraumatic diagnostic scale (PDS-5) 3 months after receiving intensive care treatment will be equally randomized to two groups: NET combined with case management and improved treatment as usual (iTAU). All primary care physicians (PCPs) involved will be instructed in the diagnosis and treatment of PTSD according to current German guidelines. PCPs in the iTAU group will deliver usual care during three consultations. In the experimental group, PCPs will additionally be trained to deliver an adapted version of NET (three sessions) supported by phone-based case management by a medical assistant. At 6 and 12 months after randomization, structured blinded telephone interviews will assess patient-reported outcomes. The primary composite endpoint is the absolute change from baseline at month 6 in PTSD symptom severity measured by the PDS-5 total score, which also incorporates the death of any study patients. Secondary outcomes cover the domains depression, anxiety, disability, health-related quality-of-life, and cost-effectiveness. The principal analysis is by intention to treat. Discussion If the superiority of the experimental intervention over usual care can be demonstrated, the combination of brief NET and case management could be a treatment option to relieve PTSD-related symptoms and to improve primary care after intensive care. Trial registration ClinicalTrials.gov, NCT03315390. Registered on 10 October 2017. German Clinical Trials Register, DRKS00012589. Registered on 17 October 2017.

Abstract Background The prevalence of pain is very common in the oldest age group. Managing pain successfully is a key topic in primary care, especially within the ageing population. Different care settings might have an impact on the prevalence of pain and everyday life. Methods Participants from the German longitudinal cohort study on Needs, Health Service Use, Costs and Health-related Quality of Life in a large Sample of Oldest-old Primary Care Patients (85+) (AgeQualiDe) were asked to rate their severity of pain as well as the impairment with daily activities. Besides gender, age, education, BMI and use of analgesics we focused on the current housing situation and on cognitive state. Associations of the dependent measures were tested using four ordinal logistic regression models. Model 1 and 4 consisted of the overall sample, model 2 and 3 were divided according to no cognitive impairment (NCI) and mild cognitive impairment (MCI). Results Results show a decline in pain at very old age but nonetheless a high prevalence among the 85+ year olds. Sixty-three per cent of the participants report mild to severe pain and 69% of the participants mild to extreme impairment due to pain with daily activities. Use of analgesics, depression and living at home with care support are significantly associated with higher and male gender with lower pain ratings. Conclusions Sufficient pain management among the oldest age group is inevitable. Outpatient care settings are at risk of overlooking pain. Therefore focus should be set on pain management in these settings.

For some time, there have been indications that the prevalence of overweight and obesity among children and adolescents in Germany has stabilised at a high level. The second wave of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS Wave 2, 2014-2017) once again provides nationwide measurements on height and weight of children and adolescents aged 3 to 17 years. The results are confirming this trend. The prevalence of overweight is 15.4% and 5.9% for obesity. There are no differences between girls and boys. Overweight and obesity prevalence increases with age. Children and adolescents with low socioeconomic status (SES) are more likely to be overweight and obese than those with high SES. Compared to the KiGGS baseline study (2003-2006), there was no further increase in overweight and obesity prevalence overall and in all age groups.