Vocational Education and Training and Transitions into the Labor Market

Stage 6 of the German National Educational Panel Study (NEPS) 6 is devoted to the transition of young people from school to work. Stage 6 focuses in particular on the transition from school to vocational education and training and then to work (for tertiary education, see Chap. 16). In all Western societies, vocational education and training (VET) systems face a number of challenges, including the need to adapt to increasing skill requirements across the economy and to handle the danger of producing an "underclass" of low-skilled youth. This chapter presents the life-course approach for investigating school-leavers' pathways from school into the labor market within NEPS. Several factors shape young people’s school-to-work transitions: their motivation and competence endowment, their decisions to apply for specific educational programs, the constraints they face regarding the opportunities for VET programs and the gatekeepers’ recruitment behavior, the information and support youths may or may not receive from social networks, and the learning environments they encounter in firms and schools. We outline the basic theories that guide our research concerning these influences and discuss how we take them into account within NEPS Stage 6. Thus, we provide an overview of the study’s research potential in the area of VET. For now, it is mainly the Scientific Use Files of Starting Cohort 4 (SC4) that provide ample opportunities for innovative interdisciplinary analyses - including analyses of students from special education schools. As the starting cohorts age, Starting Cohort 3 (SC3) has now also entered NEPS Stage 6 and its data on VET transitions will soon be available as well

GABAA-Mediated Inhibition Modulates Stimulus-Specific Adaptation in the Inferior Colliculus

The ability to detect novel sounds in a complex acoustic context is crucial for survival. Neurons from midbrain through cortical levels adapt to repetitive stimuli, while maintaining responsiveness to rare stimuli, a phenomenon called stimulus-specific adaptation (SSA). The site of origin and mechanism of SSA are currently unknown. We used microiontophoretic application of gabazine to examine the role of GABAA-mediated inhibition in SSA in the inferior colliculus, the midbrain center for auditory processing. We found that gabazine slowed down the process of adaptation to high probability stimuli but did not abolish it, with response magnitude and latency still depending on the probability of the stimulus. Blocking GABAA receptors increased the firing rate to high and low probability stimuli, but did not completely equalize the responses. Together, these findings suggest that GABAA-mediated inhibition acts as a gain control mechanism that enhances SSA by modifying the responsiveness of the neuron

Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.

BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. CONCLUSIONS: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Determinants of Patient Satisfaction After Severe Lower-Extremity Injuries

Background: In health care, increased emphasis has been placed on patient-centered care, but to our knowledge little work has been conducted to understand the influences on patient satisfaction after surgery for the treatment of severe lower-extremity injury. Our purpose was to analyze how the patient's satisfaction with the outcome correlates with other measures of outcome (clinical, functional, physical impairment, psychological impairment, and pain) and with the sociodemographic characteristics of the patient, the nature of the injury, and the treatment decisions

A Phase IIa Trial of Metformin for Colorectal Cancer Risk Reduction among Individuals with History of Colorectal Adenomas and Elevated Body Mass Index.

Obesity is associated with risk of colorectal adenoma (CRA) and colorectal cancer. The signaling pathway activated by metformin (LKB1/AMPK/mTOR) is implicated in tumor suppression in ApcMin/+ mice via metformin-induced reduction in polyp burden, increased ratio of pAMPK/AMPK, decreased pmTOR/mTOR ratio, and decreased pS6Ser235/S6Ser235 ratio in polyps. We hypothesized that metformin would affect colorectal tissue S6Ser235 among obese patients with recent history of CRA. A phase IIa clinical biomarker trial was conducted via the U.S. National Cancer Institute-Chemoprevention Consortium. Nondiabetic, obese subjects (BMI ≥30) ages 35 to 80 with recent history of CRA were included. Subjects received 12 weeks of oral metformin 1,000 mg twice every day. Rectal mucosa biopsies were obtained at baseline and end-of-treatment (EOT) endoscopy. Tissue S6Ser235 and Ki-67 immunostaining were analyzed in a blinded fashion using Histo score (Hscore) analysis. Among 32 eligible subjects, the mean baseline BMI was 34.9. Comparing EOT to baseline tissue S6Ser235 by IHC, no significant differences were observed. Mean (SD) Hscore at baseline was 1.1 (0.57) and 1.1 (0.51) at EOT; median Hscore change was 0.034 (P = 0.77). Similarly, Ki-67 levels were unaffected by the intervention. The adverse events were consistent with metformin's known side-effect profile. Among obese patients with CRA, 12 weeks of oral metformin does not reduce rectal mucosa pS6 or Ki-67 levels. Further research is needed to determine what effects metformin has on the target tissue of origin as metformin continues to be pursued as a colorectal cancer chemopreventive agent

Dietary fiber, carbohydrates, glycemic index, and glycemic load in relation to breast cancer prognosis in the HEAL cohort

Item does not contain fulltextBACKGROUND: Dietary intake of fiber, carbohydrate, glycemic index (GI), and glycemic load (GL) may influence breast cancer survival, but consistent and convincing evidence is lacking. METHODS: We investigated associations of dietary fiber, carbohydrates, GI, and GL with breast cancer prognosis among n = 688 stage 0 to IIIA breast cancer survivors in the Health, Eating, Activity, and Lifestyle (HEAL) study. Premenopausal and postmenopausal women from Western Washington State, Los Angeles County, and New Mexico participated. Usual diet was assessed with a food frequency questionnaire. Total mortality, breast cancer mortality, nonfatal recurrence, and second occurrence data were obtained from SEER (Surveillance, Epidemiology, and End Results) registries and medical records. Cox proportional hazards regression estimated multivariate-adjusted hazard ratios and 95% confidence intervals (CI). RESULTS: During a median of 6.7 years follow-up after diagnosis, n = 106 total deaths, n = 83 breast cancer-specific deaths, and n = 82 nonfatal recurrences were confirmed. We observed an inverse association between fiber intake and mortality. Multivariate-adjusted hazard rate ratios (HRR) comparing high to low intake were 0.53 (95% CI 0.23-1.23) and 0.75 (95% CI 0.43-1.31). A threshold effect was observed whereby no additional benefit was observed for intakes of 9 g/d or more. Fiber intake was suggestively inversely associated with breast cancer-specific mortality (HRR = 0.68, 95% CI 0.27-1.70) and risk of nonfatal recurrence or second occurrence (HRR = 0.68, 95% CI 0.27-1.70), but results were not statistically significant. CONCLUSION: Dietary fiber was associated with a nonsignificant inverse association with breast cancer events and total mortality. Further studies to assess and confirm this relationship are needed in order to offer effective dietary strategies for breast cancer patients. IMPACT: Increasing dietary fiber may an effective lifestyle modification strategy for breast cancer survivors