Empower Peers 4 Careers : Positive Peer Culture to prepare adolescents' career choices

For youth with special needs, where cognitive difficulties, behavioral and psychosocial issues are more common, career choice is particularly challenging. The Positive Peer Culture (PPC) approach uses the resource of peer support to systematically build social-emotional competence. Important key elements are that adolescents feel safe to share their own problems and challenges with others, to overcome difficulties and challenges, to take responsibility for their lives, and to help each other. The Empower Peers 4 Careers Project aims to apply the PPC approach to the context of career choice to promote the development of important competences for the transition from school to work. The pedagogical background of the PPC approach in the setting of career choice, as well as the required learning environments for the peers are presented. The peer group meetings are organized following a defined process through which learning forms social-emotional competence, as well as the class climate can be strengthened. In addition, the role of the moderators of the peer groups - such as class teachers or special education teachers - is examined in more detail and the concept is presented of how they are trained on topics such as resilience promotion and strengths orientation in the context of career choice preparation. The project "Empower Peers 4 Careers" will be cientifically monitored over 2 years using a quasi-experimental control group design, which includes quantitative and qualitative methods. A total of 15 classes of the 8th grade (age group: 14-year-olds) of regular and special schools as well as 10 classes as control classes are participating. The results of the evaluation will not be available until 2023. The article presents the concept with the long-term goals, the implementation and didactics, as well as the hypotheses and the procedure for the evaluation

Mobilisation of critically ill patients receiving norepinephrine: a retrospective cohort study

Background: Mobilisation and exercise intervention in general are safe and feasible in critically ill patients. For patients requiring catecholamines, however, doses of norepinephrine safe for mobilisation in the intensive care unit (ICU) are not defined. This study aimed to describe mobilisation practice in our hospital and identify doses of norepinephrine that allowed a safe mobilisation. Methods: We conducted a retrospective single-centre cohort study of 16 ICUs at a university hospital in Germany with patients admitted between March 2018 and November 2021. Data were collected from our patient data management system. We analysed the effect of norepinephrine on level (ICU Mobility Scale) and frequency (units per day) of mobilisation, early mobilisation (within 72 h of ICU admission), mortality, and rate of adverse events. Data were extracted from free-text mobilisation entries using supervised machine learning (support vector machine). Statistical analyses were done using (generalised) linear (mixed-effect) models, as well as chi-square tests and ANOVAs. Results: A total of 12,462 patients were analysed in this study. They received a total of 59,415 mobilisation units. Of these patients, 842 (6.8%) received mobilisation under continuous norepinephrine administration. Norepinephrine administration was negatively associated with the frequency of mobilisation (adjusted difference -0.07 mobilisations per day; 95% CI - 0.09, - 0.05; p 0.1). Higher compared to lower doses of norepinephrine did not lead to a significant increase in adverse events in our practice (p > 0.1). We identified that mobilisation was safe with up to 0.20 mu g/kg/min norepinephrine for out-of-bed (IMS >= 2) and 0.33 mu g/kg/min for in-bed (IMS 0-1) mobilisation. Conclusions: Mobilisation with norepinephrine can be done safely when considering the status of the patient and safety guidelines. We demonstrated that safe mobilisation was possible with norepinephrine doses up to 0.20 mu g/kg/min for out-of-bed (IMS >= 2) and 0.33 mu g/kg/min for in-bed (IMS 0-1) mobilisation

Effect of Long-Term Agricultural Management on the Soil Microbiota Influenced by the Time of Soil Sampling

Application of agrochemicals and mechanization enabled increasing agriculturalproductivity yet caused various environmental and soil health-related problems.Agricultural practices affect soil microorganisms, which are the key players of manyecosystem processes. However, less is known about whether this effect differs betweentime points. Therefore, soil was sampled in winter (without crop) and in summer (inthe presence of maize) from a long-term field experiment (LTE) in Bernburg (Germany)managed either under cultivator tillage (CT) or moldboard plow (MP) in combinationwith either intensive nitrogen (N)-fertilization and pesticides (Int) or extensive reducedN-fertilization without fungicides (Ext), respectively. High-throughput sequencing of 16SrRNA gene and fungal ITS2 amplicons showed that changes in the microbial communitycomposition were correlated to differences in soil chemical properties caused by tillagepractice. Microbial communities of soils sampled in winter differed only depending onthe tillage practice while, in summer, also a strong effect of the fertilization intensity wasobserved. A small proportion of microbial taxa was shared between soils from the twosampling times, suggesting the existence of a stable core microbiota at the LTE. Ingeneral, taxa associated with organic matter decomposition (such as Actinobacteria,Bacteroidetes, Rhizopus, and Exophiala) had a higher relative abundance under CT.Among the taxa with significant changes in relative abundances due to different long-termagricultural practices were putative pathogenic (e.g., Gibellulopsis and Gibberella) andbeneficial microbial genera (e.g., Chitinophagaceae, Ferruginibacter, and Minimedusa).In summary, this study suggests that the effects of long-term agricultural managementpractices on the soil microbiota are influenced by the soil sampling time, and this needsto be kept in mind in future studies for the interpretation of field data.Fil: Fernandez Gnecco, Gabriela Amancay. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; ArgentinaFil: Covacevich, Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; ArgentinaFil: Consolo, Verónica Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; ArgentinaFil: Behr, Jan H.. Leibniz Institute Of Vegetable And Ornamental Crops (; AlemaniaFil: Sommermann, Loreen. Department Of Agriculture, Ecotrophology And Landscape; AlemaniaFil: Moradtalab, Narges. Department Of Nutritional Crop Physiology, Institute Of; AlemaniaFil: Maccario, Lorrie. Section Of Microbiology, Department Of Biology, Univers; AlemaniaFil: Sørensen, Søren J.. Section Of Microbiology, Department Of Biology, Univers; AlemaniaFil: Deubel, Annette. Department Of Agriculture, Ecotrophology And Landscape; AlemaniaFil: Schellenberg, Ingo. Department Of Agriculture, Ecotrophology And Landscape; AlemaniaFil: Geistlinger, Joerg. Department Of Agriculture, Ecotrophology And Landscape; AlemaniaFil: Neumann, Günter. Department Of Nutritional Crop Physiology, Institute Of; AlemaniaFil: Grosch, Rita. Leibniz Institute Of Vegetable And Ornamental Crops (; AlemaniaFil: Smalla, Kornelia. Julius Kühn Institut Braunschweig; AlemaniaFil: Babin, Doreen. Julius Kühn Institut Braunschweig; Alemani

Genome-scan for IQ discrepancy in autism: evidence for loci on chromosomes 10 and 16

Performance IQ (PIQ) greater than verbal IQ (VIQ) is often observed in studies of the cognitive abilities of autistic individuals. This characteristic is correlated with social and communication impairments, key parts of the autism diagnosis. We present the first genetic analyses of IQ discrepancy (PIQ–VIQ) as an autism-related phenotype. We performed genome-wide joint linkage and segregation analyses on 287 multiplex families, using a Markov chain Monte Carlo approach. Genetic data included a genome-scan of 387 micro-satellite markers in 210 families augmented with additional markers added in a subset of families. Empirical P values were calculated for five interesting regions. Linkage analysis identified five chromosomal regions with substantial regional evidence of linkage; 10p12 [P = 0.001; genome-wide (gw) P = 0.05], 16q23 (P = 0.015; gw P = 0.53), 2p21 (P = 0.03, gw P = 0.78), 6q25 (P = 0.047, gw P = 0.91) and 15q23–25 (P = 0.053, gw P = 0.93). The location of the chromosome 10 linkage signal coincides with a region noted in a much earlier genome-scan for autism, and the chromosome 16 signal coincides exactly with a linkage signal for non-word repetition in specific language impairment. This study provides strong evidence for a QTL influencing IQ discrepancy in families with autistic individuals on chromosome 10, and suggestive evidence for a QTL on chromosome 16. The location of the chromosome 16 signal suggests a candidate gene, CDH13, a T-cadherin expressed in the brain, which has been implicated in previous SNP studies of autism and ADHD

A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer's disease

A genome-wide survival analysis of 14,406 Alzheimer's disease (AD) cases and 25,849 controls identified eight previously reported AD risk loci and 14 novel loci associated with age at onset. Linkage disequilibrium score regression of 220 cell types implicated the regulation of myeloid gene expression in AD risk. The minor allele of rs1057233 (G), within the previously reported CELF1 AD risk locus, showed association with delayed AD onset and lower expression of SPI1 in monocytes and macrophages. SPI1 encodes PU.1, a transcription factor critical for myeloid cell development and function. AD heritability was enriched within the PU.1 cistrome, implicating a myeloid PU.1 target gene network in AD. Finally, experimentally altered PU.1 levels affected the expression of mouse orthologs of many AD risk genes and the phagocytic activity of mouse microglial cells. Our results suggest that lower SPI1 expression reduces AD risk by regulating myeloid gene expression and cell function

Convergent genetic and expression data implicate immunity in Alzheimer's disease

Background Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics

A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele