Perovskite-organic tandem solar cells with indium oxide interconnect.

Multijunction solar cells can overcome the fundamental efficiency limits of single-junction devices. The bandgap tunability of metal halide perovskite solar cells renders them attractive for multijunction architectures1. Combinations with silicon and copper indium gallium selenide (CIGS), as well as all-perovskite tandem cells, have been reported2-5. Meanwhile, narrow-gap non-fullerene acceptors have unlocked skyrocketing efficiencies for organic solar cells6,7. Organic and perovskite semiconductors are an attractive combination, sharing similar processing technologies. Currently, perovskite-organic tandems show subpar efficiencies and are limited by the low open-circuit voltage (Voc) of wide-gap perovskite cells8 and losses introduced by the interconnect between the subcells9,10. Here we demonstrate perovskite-organic tandem cells with an efficiency of 24.0 per cent (certified 23.1 per cent) and a high Voc of 2.15 volts. Optimized charge extraction layers afford perovskite subcells with an outstanding combination of high Voc and fill factor. The organic subcells provide a high external quantum efficiency in the near-infrared and, in contrast to paradigmatic concerns about limited photostability of non-fullerene cells11, show an outstanding operational stability if excitons are predominantly generated on the non-fullerene acceptor, which is the case in our tandems. The subcells are connected by an ultrathin (approximately 1.5 nanometres) metal-like indium oxide layer with unprecedented low optical/electrical losses. This work sets a milestone for perovskite-organic tandems, which outperform the best p-i-n perovskite single junctions12 and are on a par with perovskite-CIGS and all-perovskite multijunctions13.

Dynamic slab segmentation due to brittle-ductile damage in the outer rise.

Subduction is the major plate driving force, and the strength of the subducting plate controls many aspects of the thermochemical evolution of Earth. Each subducting plate experiences intense normal faulting1-9 during bending that accommodates the transition from horizontal to downwards motion at the outer rise at trenches. Here we investigate the consequences of this bending-induced plate damage using numerical subduction models in which both brittle and ductile deformation, including grain damage, are tracked and coupled self-consistently. Pervasive slab weakening and pronounced segmentation can occur at the outer-rise region owing to the strong feedback between brittle and ductile damage localization. This slab-damage phenomenon explains the subduction dichotomy of strong plates and weak slabs10, the development of large-offset normal faults6,7 near trenches, the occurrence of segmented seismic velocity anomalies11 and distinct interfaces imaged within subducted slabs12,13, and the appearance of deep, localized intraplate areas of reduced effective viscosity14 observed at trenches. Furthermore, brittle-viscously damaged slabs show a tendency for detachment at elevated mantle temperatures. Given Earth's planetary cooling history15, this implies that intermittent subduction with frequent slab break-off episodes16 may have been characteristic for Earth until more recent times than previously suggested17.

The unexpected surface of asteroid (101955) Bennu.

NASA'S Origins, Spectral Interpretation, Resource Identification and Security-Regolith Explorer (OSIRIS-REx) spacecraft recently arrived at the near-Earth asteroid (101955) Bennu, a primitive body that represents the objects that may have brought prebiotic molecules and volatiles such as water to Earth1. Bennu is a low-albedo B-type asteroid2 that has been linked to organic-rich hydrated carbonaceous chondrites3. Such meteorites are altered by ejection from their parent body and contaminated by atmospheric entry and terrestrial microbes. Therefore, the primary mission objective is to return a sample of Bennu to Earth that is pristine-that is, not affected by these processes4. The OSIRIS-REx spacecraft carries a sophisticated suite of instruments to characterize Bennu's global properties, support the selection of a sampling site and document that site at a sub-centimetre scale5-11. Here we consider early OSIRIS-REx observations of Bennu to understand how the asteroid's properties compare to pre-encounter expectations and to assess the prospects for sample return. The bulk composition of Bennu appears to be hydrated and volatile-rich, as expected. However, in contrast to pre-encounter modelling of Bennu's thermal inertia12 and radar polarization ratios13-which indicated a generally smooth surface covered by centimetre-scale particles-resolved imaging reveals an unexpected surficial diversity. The albedo, texture, particle size and roughness are beyond the spacecraft design specifications. On the basis of our pre-encounter knowledge, we developed a sampling strategy to target 50-metre-diameter patches of loose regolith with grain sizes smaller than two centimetres4. We observe only a small number of apparently hazard-free regions, of the order of 5 to 20 metres in extent, the sampling of which poses a substantial challenge to mission success.

Primordial helium entrained by the hottest mantle plumes.

Helium isotopes provide an important tool for tracing early-Earth, primordial reservoirs that have survived in the planet's interior. Volcanic hotspot lavas, like those erupted at Hawaii and Iceland, can host rare, high 3He/4He isotopic ratios (up to 50 times the present atmospheric ratio, Ra) compared to the lower 3He/4He ratios identified in mid-ocean-ridge basalts that form by melting the upper mantle (about 8Ra; ref. 5). A long-standing hypothesis maintains that the high-3He/4He domain resides in the deep mantle, beneath the upper mantle sampled by mid-ocean-ridge basalts, and that buoyantly upwelling plumes from the deep mantle transport high-3He/4He material to the shallow mantle beneath plume-fed hotspots. One problem with this hypothesis is that, while some hotspots have 3He/4He values ranging from low to high, other hotspots exhibit only low 3He/4He ratios. Here we show that, among hotspots suggested to overlie mantle plumes, those with the highest maximum 3He/4He ratios have high hotspot buoyancy fluxes and overlie regions with seismic low-velocity anomalies in the upper mantle, unlike plume-fed hotspots with only low maximum 3He/4He ratios. We interpret the relationships between 3He/4He values, hotspot buoyancy flux, and upper-mantle shear wave velocity to mean that hot plumes-which exhibit seismic low-velocity anomalies at depths of 200 kilometres-are more buoyant and entrain both high-3He/4He and low-3He/4He material. In contrast, cooler, less buoyant plumes do not entrain this high-3He/4He material. This can be explained if the high-3He/4He domain is denser than low-3He/4He mantle components hosted in plumes, and if high-3He/4He material is entrained from the deep mantle only by the hottest, most buoyant plumes. Such a dense, deep-mantle high-3He/4He domain could remain isolated from the convecting mantle, which may help to explain the preservation of early Hadean (>4.5 billion years ago) geochemical anomalies in lavas sampling this reservoir.

[Implementation of the principle of supported employment in Germany : Position paper of a task force of the DGPPN]. / Umsetzung der Prinzipien des Supported Employment in Deutschland : Positionspapier einer Task-Force der DGPPN.

The effects of mental diseases on the employment and working situation can be substantial. They are one of the main reasons for inability to work and reduced earning capacity. Against this background the question arises about suitable occupational reintegration measures for people with severe mental illnesses. In recent years, the principle of supported employment has been internationally shown to be increasingly more successful. In this context mentally ill people are primarily placed at a position of the first employment market and supported on-site by a job coach. This concept is inclusive, individual and evidence based. Despite proven effectiveness, it has so far been insufficiently implemented in German-speaking regions. In the future it will be a matter of considering the individual needs for assistance of mentally ill people more intensively than previously and to respond with functional and in a best-case scenario, multiprofessional and flexible offers.

An enhanced prognostic score for overall survival of patients with cancer derived from a large real-world cohort.

BACKGROUND: By understanding prognostic biomarkers, we gain insights into disease biology and may improve design, conduct, and data analysis of clinical trials and real-world data. In this context, we used the Flatiron Health Electronic Health Record-derived deidentified database that provides treatment outcome and biomarker data from >280 oncology centers in the USA, organized into 17 cohorts defined by cancer type. PATIENTS AND METHODS: In 122 694 patients, we analyzed demographic, clinical, routine hematology, and blood chemistry parameters within a Cox proportional hazard framework to derive a multivariable prognostic risk model for overall survival (OS), the 'Real wOrld PROgnostic score (ROPRO)'. We validated ROPRO in two independent phase I and III clinical studies. RESULTS: A total of 27 variables contributed independently and homogeneously across cancer indications to OS. In the largest cohort (advanced non-small-cell lung cancer), for example, patients with elevated ROPRO scores (upper 10%) had a 7.91-fold (95% confidence interval 7.45-8.39) increased death hazard compared with patients with low scores (lower 10%). Median survival was 23.9 months (23.3-24.5) in the lowest ROPRO quartile Q1, 14.8 months (14.4-15.2) in Q2, 9.4 months (9.1-9.7) in Q3, and 4.7 months (4.6-4.8) in Q4. The ROPRO model performance indicators [C-index = 0.747 (standard error 0.001), 3-month area under the curve (AUC) = 0.822 (0.819-0.825)] strongly outperformed those of the Royal Marsden Hospital Score [C-index = 0.54 (standard error 0.0005), 3-month AUC = 0.579 (0.577-0.581)]. We confirmed the high prognostic relevance of ROPRO in clinical Phase 1 and III trials. CONCLUSIONS: The ROPRO provides improved prognostic power for OS. In oncology clinical development, it has great potential for applications in patient stratification, patient enrichment strategies, data interpretation, and early decision-making in clinical studies.

Application of confocal, SHG and atomic force microscopy for characterizing the structure of the most superficial layer of articular cartilage.

The surface of articular cartilage plays a crucial role in attenuating and transmitting mechanical loads in synovial joints to facilitate painless locomotion. Disruption to the surface of articular cartilage causes changes to its frictional properties instigating the deterioration of the tissue. In this study, we physically peeled the most superficial layer, a transparent membrane of 20.0 ± 4.7 µm thick, from the central loading region of femoral condyles of sheep. The ultrastructure of this layer without interference from the underlying cartilage was independently investigated using confocal, second harmonic generation and atomic force microscopy. We found that the most superficial layer contains chondrocytes, densely packed collagen, coarse elastic fibres and a fine elastic network. The elastic fibres are most prevalent at the surface of the layer, where collagen and chondrocyte densities are lowest. At the interface of this most superficial layer with the underlying bulk cartilage, a dense fibrillar network exists, formed mainly by collagen fibrils and elastin microfibrils. By contrast, the interface of the underlying cartilage with the most superficial layer contains collagen fibrils, fine microfibrils and microfibrils distinctively laced on one side. The findings of this study will play an important role in understanding the mechanical function and wear resistance of articular cartilage, and in developing more promising tissue engineering techniques to treat cartilage defects and osteoarthritis. LAY DESCRIPTION: The chronic pain and dysfuction in synovial joints caused by osteoarthritis can have a debilitating impact on daily activities for sufferers. Osteoarthritis is characterised by the deterioration of the articular cartilage. Despite intensive research, the wear mechanism of articular cartilage and the progression of osteoarthritis remain unclear in the literature. Articular cartilage is a resilient tissue that provides a low friction surface to facilitate painless locomotion. The surface of articular cartilage plays a crucial role in attenuating and transmitting mechanical loads. Disruption at the surface of articular cartilage causes changes to its frictional properties, instigating the deterioration of the tissue. Despite this, the definition of the most superficial layer of articular cartilage, as well as its composition and microstructure, have endured a long history of debate, clouding our understanding of the early progression of osteoarthritis. In order to investigate the surface of articular cartilage independently from the underlying cartilage, we physically peeled a transparent membrane of 20.0 ± 4.7 µm thickness, the most superficial layer, from the central loading region of the femoral condyles of sheep. Using confocal, second harmonic generation and atomic force microscopy, we found that the most superficial layer contains cartilage cells (chondrocytes), densely packed collagen, coarse elastic fibres and a fine elastic network. The coarse elastic fibres are most prevalent at the surface of the layer where collagen and chondrocyte densities are lowest. Furthermore, we investigated the surfaces at the interface of the most superficial layer with the underlying articular cartilage. At the interface of this most superficial layer with the underlying bulk cartilage, a dense fibrillar network exists, formed mainly by collagen fibrils and elastin microfibrils. In contrast, the interface of the underlying cartilage with the most superficial layer contains collagen fibrils, fine microfibrils and microfibrils distinctively laced on one side. The findings of this study have confirmed that there is a most superficial layer that is able to be removed using a tangential force. Through the application of advanced imaging technologies, we have shown that this most superficial layer is cellular and have detailed its composition and ultrastructure. Due to the close association between the form and function of tissues, the findings of this study will play an important role in understanding the mechanical function and wear mechanism of articular cartilage. This may lead to the development of more promising tissue engineering techniques to treat cartilage defects and osteoarthritis.

Expert consensus on a train-the-trainer curriculum for robotic colorectal surgery.

AIM: Robotic techniques are being increasingly used in colorectal surgery. There is, however, a lack of training opportunities and structured training programmes. Robotic surgery has specific problems and challenges for trainers and trainees. Ergonomics, specific skills and user-machine interfaces are different from those in traditional laparoscopic surgery. The aim of this study was to establish expert consensus on the requirements for a robotic train-the-trainer curriculum amongst robotic surgeons and trainers. METHOD: This is a modified Delphi-type study involving 14 experts in robotic surgery teaching. A reiterating 19-item questionnaire was sent out to the same group and agreement levels analysed. A consensus of 0.8 or higher was considered to be high-level agreement. RESULTS: Response rates were 93-100% and most items reached high levels of agreement within three rounds. Specific requirements for a robotic faculty development curriculum included maximizing dual-console teaching, theatre team training, nontechnical skills training, patient safety, user-machine interface training and telementoring. CONCLUSION: A clear need for the development of a train-the-trainer curriculum has been identified. Further research is needed to assess feasibility, effectiveness and clinical impact of a robotic train-the-trainer curriculum.

No augmentation of indoleamine 2,3-dioxygenase (IDO) activity through belatacept treatment in liver transplant recipients.

Belatacept is a second-generation cytotoxic T lymphocyte antigen (CTLA)-4 immunoglobulin (Ig) fusion protein approved for immunosuppression in renal transplant recipients. It was designed intentionally to interrupt co-stimulation via CD28 by binding to its ligands B7·1 and B7·2. Experimental evidence suggests a potential additional mechanism for CTLA-4 Ig compounds through binding to B7 molecules expressed on antigen-presenting cells (APCs) and up-regulation of indoleamine 2,3-dioxygenase (IDO), an immunomodulating enzyme that catalyzes the degradation of tryptophan to kynurenine and that down-regulates T cell immunity. So far it remains unknown whether belatacept up-regulates IDO in transplant recipients. We therefore investigated whether belatacept therapy enhances IDO activity in liver transplant recipients enrolled in a multi-centre, investigator-initiated substudy of the Phase II trial of belatacept in liver transplantation (IM103-045). Tryptophan and kynurenine serum levels were measured during the first 6 weeks post-transplant in liver transplant patients randomized to receive either belatacept or tacrolimus-based immunosuppression. There was no significant difference in IDO activity, as indicated by the kynurenine/tryptophan ratio, between belatacept and tacrolimus-treated patients in per-protocol and in intent-to-treat analyses. Moreover, no evidence was found that belatacept affects IDO in human dendritic cells (DC) in vitro. These data provide evidence that belatacept is not associated with detectable IDO induction in the clinical transplant setting compared to tacrolimus-treated patients.

Induced expression of the alcohol acetyltransferase gene ATF1 in industrial yeast Saccharomyces pastorianus TUM 34/70.

Targeted induced gene expression for industrial fermentation processes in food and beverage production could fulfill future demands. To avoid metabolic burden and disturbances owing to the fermentation procedure, induced gene expression is necessary for combating stress, such as that caused by temperature shifts that occur during the transition from fermentation to maturation in the brewing process. The aim of this study was to target gene expression in industrial yeast using stress-responsive promoters and homologues of the selection marker SMR1. Self-cloning strains of the industrial brewing yeast Saccharomyces pastorianus TUM 34/70 were constructed to overexpress the alcohol acetyltransferase (ATF1) gene under the control of inducible promoters P SSA3, P HSP104 and P UBI4. Transcription analysis shows the highest induction after 72 h of shock situation for P HSP104 with 1.3-fold and P UBI4 with 2.2-fold. Further, at the end of shock situation the concentrations of ethyl acetate were 1.2- and 1.3-fold higher than the wild type for P HSP104 and P UBI4, respectively. In addition, the influence of the final temperature and temporal sequence of temperature shock to 4°C had a major impact on expression patterns. Therefore, these data show that temperature-induced gene expression of self-cloning industrial yeast could be an option for optimization of the beverage fermentation.

Genome-wide significant risk factors for Alzheimer's disease: role in progression to dementia due to Alzheimer's disease among subjects with mild cognitive impairment.

Few data are available concerning the role of risk markers for Alzheimer's disease (AD) in progression to AD dementia among subjects with mild cognitive impairment (MCI). We therefore investigated the role of well-known AD-associated single-nucleotide polymorphism (SNP) in the progression from MCI to AD dementia. Four independent MCI data sets were included in the analysis: (a) the German study on Aging, Cognition and Dementia in primary care patients (n=853); (b) the German Dementia Competence Network (n=812); (c) the Fundació ACE from Barcelona, Spain (n=1245); and (d) the MCI data set of the Amsterdam Dementia Cohort (n=306). The effects of single markers and combined polygenic scores were measured using Cox proportional hazards models and meta-analyses. The clusterin (CLU) locus was an independent genetic risk factor for MCI to AD progression (CLU rs9331888: hazard ratio (HR)=1.187 (1.054-1.32); P=0.0035). A polygenic score (PGS1) comprising nine established genome-wide AD risk loci predicted a small effect on the risk of MCI to AD progression in APOE-ɛ4 (apolipoprotein E-ɛ4) carriers (HR=1.746 (1.029-2.965); P=0.038). The novel AD loci reported by the International Genomics of Alzheimer's Project were not implicated in MCI to AD dementia progression. SNP-based polygenic risk scores comprising currently available AD genetic markers did not predict MCI to AD progression. We conclude that SNPs in CLU are potential markers for MCI to AD progression.

Differences in the placebo response in duloxetine and venlafaxine trials.

OBJECTIVE: Our analysis aimed at comparing the placebo effect sizes from randomized controlled trials (RCTs) of two widely prescribed antidepressants, namely duloxetine and venlafaxine, and at analysing a potential influence of the investigated drugs on the placebo response. METHOD: We conducted a comprehensive systematic review and meta-analysis of placebo-controlled, double-blind RCTs, which examined the efficacy of duloxetine and venlafaxine in the acute treatment of major depressive disorder. RESULTS: We included 71 studies (29 duloxetine trials and 43 venlafaxine trials; one study provided data for the duloxetine and the venlafaxine data set). The placebo effect sizes, defined as pre-postscore change divided by baseline standard deviation, differed significantly between venlafaxine and duloxetine studies (-2.51 vs. -2.09; test for subgroup differences P = 0.028; high heterogeneity). The analysis of effect modifiers and the metaregression analyses confirmed the drug, next to baseline depression severity and publication status, as the most influential independent predictor. CONCLUSION: Our analyses show a significant difference in the placebo response between venlafaxine and duloxetine trials and suggest that the investigated drug has an influence on the placebo response that is not related to baseline severity, changes over the years or other variables we included.

Duodenal intussusception of the remnant stomach after biliopancreatic diversion: a case report.

BACKGROUND: We present a rare case of an antegrade intussusception of the remnant stomach four years after a biliopancreatic diversion. CASE PRESENTATION: A 55-year-old female patient presented with epigastric pain in our emergency room. Laboratory parameters showed an anemia as well as elevated transaminases and hyperbilirubinemia. The CT scan showed an intussusception of the remnant stomach into the duodenum followed by cholestasis. At laparotomy the remnant stomach was resected. CONCLUSION: Bowel obstruction and intussusception after bariatric surgery are a rare but often unrecognized complication. Sonography as well as a CT scan should be performed. The exploratory laparoscopy however is the most valuable diagnostic tool in patients with suspected intussusception, due to the high rate of non-specific symptoms and misinterpreted radiographic investigations.

[Life-threatening metabolic acidosis after ingestion of fire extinguisher powder]. / Lebensbedrohliche Acidose nach Ingestion von ABC-Löschpulver.

We present the case of a 31-year old male with ingestion of fire extinguisher powder in an attempted suicide. After consulting several poison information centres, the intoxication was initially classified as harmless; nevertheless, the patient was admitted to our intensive care unit for cardiopulmonary monitoring. Subsequently, due to the ingestion of ammonium sulphate and ammonium dihydrogen phosphate containing powder the patient developed severe metabolic acidosis with distinct electrolyte imbalance that required temporary haemodialysis.

[Performance of prehospital emergency anesthesia and airway management : An online survey]. / Durchführung einer prähospitalen Notfallnarkose und Atemwegssicherung : Eine Onlineumfrage.

BACKGROUND: The goal of rapid sequence induction (RSI) in cases of emergency situations is to secure the airway as quickly as possible to prevent pulmonary aspiration of gastric contents; however, the technique itself is not standardized. For example, the choice of drugs, application of cricoid pressure and the patient position remain controversial. A survey of emergency medical services (EMS) physicians throughout Germany was carried out to assess the different RSI techniques used and with respect to complying with the national guidelines for emergency airway management anesthesia and local standard operating procedures (SOP). MATERIAL AND METHODS: Between 1 April 2017 and 31 May 2017, EMS medical directors in Germany were contacted and asked to distribute a 28-question online questionnaire to local EMS physicians. Of the questions 26 were multiple choice and 2 with plain text. After 6 weeks an e­mail reminder was sent. In addition, the survey was distributed via social media to EMS physicians. RESULTS: In total the survey was opened 2314 times and 1074 completed responses were received (completion rate 46%). Most of the participants were male (78%) and anesthesiologists (70%) and only one quarter had a local SOP for RSI. The most frequently used muscle relaxant was succinylcholine (62%) and over half of the participants reported using cricoid pressure (57%). There was a distinction between the specialist disciplines in the selection of drugs. Propofol was used most by anesthesiologists, while the others still used etomidate on a larger scale. Nearly 100% could fall back on supraglottic devices (one third laryngeal mask, two thirds laryngeal tube) but only 32.8% with the recommended esophageal drainage. A video laryngoscope was available to 51% of all EMS physicians surveyed. CONCLUSION: The results of the survey demonstrate heterogeneity in RSI techniques used by EMS physicians in Germany. Medical equipment and safe care practices, such as labeling of syringes varied considerably between different service areas. The recommendations of the S1 national guidelines on emergency airway management and anesthesia should be adhered to together with the implementation of local SOPs.

[On the road to psychiatric reform : Reconstructing the political preparation of the first Enquete Commission of the German Bundestag]. / Der Weg zur Psychiatrie-Enquete : Rekonstruktion der politischen Vorbereitung der ersten Enquetekommission des Deutschen Bundestags.

BACKGROUND: The purpose of this paper is to analyze the political preparation of the Enquete Commission of the German Bundestag which aimed at assessing and improving the psychiatric and psychotherapeutic/psychosomatic care in the Federal Republic of Germany. METHODS: We performed a selective literature review and a hermeneutic analysis of political, parliamentary and administrative records from public archives which reflect and help reconstruct the run-up process to the so-called Enquete of psychiatry. RESULTS: Literature and documents show how individual actors both in the mental health professions and politics bundled activities in the domains of psychiatry and mental health care as well as health/social politics; they helped to implement political, parliamentary and administrative steps leading up to the Enquete of the German Bundestag (1971-1975). In addition, the records and pertinent literature document the social, cultural and political developments in the Federal Republic of Germany which helped initiate the Enquete project. CONCLUSION: The Enquete was not a straightforward process and was also not tied to any moment. It fits more into the longer-term reform process of psychiatry in the Federal Republic of Germany.

[Hebephrenia - a viable psychopathological construct?] / Hebephrenie ­ ein brauchbares psychopathologisches Konstrukt?

Ewald Hecker was the first psychiatrist to describe the disease entity of hebephrenia in some detail, focusing mainly on disturbances of affect. Later Emil Kraepelin and Eugen Bleuler saw hebephrenia as a subtype of dementia praecox or schizophrenia. Willy Mayer-Gross and Karl Leonhard characterized hebephrenia with highly differentiated psychopathological descriptions, whereas this construct only played a minor role in the works of Klaus Conrad and Kurt Schneider. The International Classification of Diseases (ICD-10) lists hebephrenia as a subtype of schizophrenia but in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) no subtypes of schizophrenia are mentioned and the concept of hebephrenia is thus lost. Hebephrenia can be seen as an ideal type describing a psychopathological course pattern. This construct can be useful to conceptualize a group of disorders of affect which otherwise escape description, especially since these psychopathological alterations of affect are difficult to operationalize. To have a viable concept of these disorders is relevant for the prognosis and therapy planning. If the concept of hebephrenia is abolished, important psychopathological knowledge might be lost for future generations of psychiatrists.

[The German Association for Psychiatry, Psychotherapy and Psychosomatics participation compass II : Implementation of social participation for people with mental illnesses]. / Der DGPPN-Teilhabekompass II : Umsetzung sozialer Teilhabe für Menschen mit psychischen Erkrankungen.

For most people living with mental illnesses, participating in society is of existential importance; however, psychosocial care often fails to recognize its significance and therefore rarely includes the patient's interaction with society in the course of treatment. The reasons for this are both substantial and organizational in nature. The endless opportunities for participating in society, current areas as well as ways of taking part in social life even beyond the terms of the social legislative definition are, in addition to institutional variety and regional differences, all too often barriers to providing the very urgently needed support. Further aspects are insufficient knowledge of therapists about established options of rehabilitative treatment and about responsibilities related to participation in specialized training and further education for professional caregivers. The presented compass of participation for social integration of persons with mental illnesses starts at this point: it provides guidelines for psychiatric and psychotherapeutic practitioners, general practitioners as well as for physicians working in residential or day care institutions with a psychiatric and psychotherapeutic background. Both this article and planned online versions should help professionals to timely and successfully assist people, particularly those with severe mental illnesses, to navigate the broad spectrum of services for social and vocational integration in Germany.

Efficacy and Safety Outcomes of Extended Criteria Donor Kidneys by Subtype: Subgroup Analysis of BENEFIT-EXT at 7 Years After Transplant.

The phase III Belatacept Evaluation of Nephroprotection and Efficacy as First-Line Immunosuppression Trial-Extended Criteria Donors Trial (BENEFIT-EXT) study compared more or less intensive belatacept-based immunosuppression with cyclosporine (CsA)-based immunosuppression in recipients of extended criteria donor kidneys. In this post hoc analysis, patient outcomes were assessed according to donor kidney subtype. In total, 68.9% of patients received an expanded criteria donor kidney (United Network for Organ Sharing definition), 10.1% received a donation after cardiac death kidney, and 21.0% received a kidney with an anticipated cold ischemic time ≥24 h. Over 7 years, time to death or graft loss was similar between belatacept- and CsA-based immunosuppression, regardless of donor kidney subtype. In all three donor kidney cohorts, estimated mean GFR increased over months 1-84 for belatacept-based treatment but declined for CsA-based treatment. The estimated differences in GFR significantly favored each belatacept-based regimen versus the CsA-based regimen in the three subgroups (p < 0.0001 for overall treatment effect). No differences in the safety profile of belatacept were observed by donor kidney subtype.

A novel Alzheimer disease locus located near the gene encoding tau protein.

APOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ɛ4+ (10 352 cases and 9207 controls) and APOE ɛ4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ɛ4 status. Suggestive associations (P<1 × 10(-4)) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ɛ4+: 1250 cases and 536 controls; APOE ɛ4-: 718 cases and 1699 controls). Among APOE ɛ4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10(-9)). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ɛ4+ subjects (CR1 and CLU) or APOE ɛ4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10(-7)) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P ⩽ 1.3 × 10(-8)), frontal cortex (P ⩽ 1.3 × 10(-9)) and temporal cortex (P⩽1.2 × 10(-11)). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10(-6)) and temporal cortex (P=2.6 × 10(-6)). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ɛ4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted.