Does transition from an unstable labour market position to permanent employment protect mental health? Results from a 14-year follow-up of school-leavers

<p>Abstract</p> <p>Background</p> <p>Having secure employment, in contrast to being unemployed, is regarded as an important determinant of health. Research and theories about the negative health consequences of unemployment indicated that transition from unemployment to a paid job could lead to improved health. The objective of this study was to test the hypothesis that obtaining permanent employment after being in an unstable labour market position protects mental health.</p> <p>Methods</p> <p>A 14-year follow-up of all graduates from compulsory school in an industrial town in northern Sweden was performed at ages 16, 18, 21 and 30 years. Complete data on the cohort were collected for 1044 individuals with the aid of a comprehensive questionnaire. The response rate was 96.4%. The health measurement used in this study was the psychological symptoms analysed by multivariate logistic regression. Those who obtained permanent employment were the focus of the analysis. This group consisted of people who were in an unstable labour market position for a year or more between the ages of 25 and 29, and who had acquired a permanent job one year before and at the time of the investigation.</p> <p>Results</p> <p>After controlling for gender as well as for an indicator of health-related selection, possible confounders and mediators, an association was found between the lower probability of psychological symptoms and obtaining permanent employment (OR = 0.35, 95% CI 0.19–0.63) as well as having permanent employment (OR = 0.22, 95% CI 0.10–0.51).</p> <p>Conclusion</p> <p>Our findings suggest that transition from an unstable labour market position to permanent employment could be health-promoting, even after controlling for possible confounders and mediators, as well as for an indicator of health-related selection. However, as there are few studies in the field, there is a need for more longitudinal studies in order to further analyse the relationship and to examine possible explanations. The policy implication of our study is that the transformation of unstable labour market positions into permanent employment could contribute to better public health.</p

Sound-meaning association biases evidenced across thousands of languages

It is widely assumed that one of the fundamental properties of spoken language is the arbitrary relation between sound and meaning. Some exceptions in the form of nonarbitrary associations have been documented in linguistics, cognitive science, and anthropology, but these studies only involved small subsets of the 6,000+ languages spoken in the world today. By analyzing word lists covering nearly two-thirds of the world's languages, we demonstrate that a considerable proportion of 100 basic vocabulary items carry strong associations with specific kinds of human speech sounds, occurring persistently across continents and linguistic lineages (linguistic families or isolates). Prominently among these relations, we find property words ("small" and i, "full" and p or b) and body part terms ("tongue" and l, "nose" and n). The areal and historical distribution of these associations suggests that they often emerge independently rather than being inherited or borrowed. Our results therefore have important implications for the language sciences, given that nonarbitrary associations have been proposed to play a critical role in the emergence of cross-modal mappings, the acquisition of language, and the evolution of our species' unique communication system

Inequalities of quality of life in unemployed young adults: A population-based questionnaire study

BACKGROUND: It is well known that unemployment is a great problem both to the exposed individual and to the whole society. Unemployment is reported as more common among young people compared to the general level of unemployment. Inequity in health status and life-satisfaction is related to unemployment. The purpose of this population-based study was to describe QOL among unemployed young people compared to those who are not unemployed, and to analyse variables related to QOL for the respective groups. METHODS: The sample consisted of 264 young unemployed individuals and 528 working or studying individuals as a reference group. They all received a questionnaire about civil status, educational level, immigration, employment status, self-reported health, self-esteem, social support, social network, spare time, dwelling, economy and personal characteristics. The response rate was 72%. The significance of differences between proportions was tested by Fisher's exact test or by χ(2 )test. Multivariate analysis was carried out by means of a logistic regression model. RESULTS: Our results balance the predominant picture of youth unemployment as a principally negative experience. Although the unemployed reported lower levels of QOL than the reference group, a majority of unemployed young adults reported good QOL, and 24% even experienced higher QOL after being unemployed. Positive QOL related not only to good health, but also to high self-esteem, satisfaction with spare time and broad latitude for decision-making. CONCLUSION: Even if QOL is good among a majority of unemployed young adults, inequalities in QOL were demonstrated. To create more equity in health, individuals who report reduced subjective health, especially anxiety need extra attention and support. Efforts should aim at empowering unemployed young adults by identifying their concerns and resources, and by creating individual programmes in relation not only to education and work, but also to personal development

A global analysis of matches and mismatches between human genetic and linguistic histories

Human history is written in both our genes and our languages. The extent to which our biological and linguistic histories are congruent has been the subject of considerable debate, with clear examples of both matches and mismatches. To disentangle the patterns of demographic and cultural transmission, we need a global systematic assessment of matches and mismatches. Here, we assemble a genomic database (GeLaTo, or Genes and Languages Together) specifically curated to investigate genetic and linguistic diversity worldwide. We find that most populations in GeLaTo that speak languages of the same language family (i.e., that descend from the same ancestor language) are also genetically highly similar. However, we also identify nearly 20% mismatches in populations genetically close to linguistically unrelated groups. These mismatches, which occur within the time depth of known linguistic relatedness up to about 10,000 y, are scattered around the world, suggesting that they are a regular outcome in human history. Most mismatches result from populations shifting to the language of a neighboring population that is genetically different because of independent demographic histories. In line with the regularity of such shifts, we find that only half of the language families in GeLaTo are genetically more cohesive than expected under spatial autocorrelations. Moreover, the genetic and linguistic divergence times of population pairs match only rarely, with Indo-European standing out as the family with most matches in our sample. Together, our database and findings pave the way for systematically disentangling demographic and cultural history and for quantifying processes of shifts in language and social identities on a global scale

Expanding clinical phenotype and novel insights into the pathogenesis of ICOS deficiency

Background: Inducible T cell co-stimulator (ICOS) deficiency has been categorized as a combined immunodeficiency often complicated by enteropathies, autoimmunity, lymphoproliferation, and malignancy. We report seven new patients and four novel ICOS mutations resulting in a common variable immunodeficiency (CVID)–like phenotype and show that dysregulated IL-12 release, reduced cytotoxic T lymphocyte–associated protein 4 (CTLA4) expression, and skewing towards a Th1-dominant phenotype are all associated with inflammatory complications in this condition. Methods: A combination of whole exome and Sanger sequencing was used to identify novel mutations. Standard clinical and immunological evaluation was performed. FACS and ELISA-based assays were used to study cytokine responses and ICOS/ICOSL/CTLA4 expression following stimulation of whole blood and PBMCs with multiple TLR ligands, anti-CD3, and PHA. Results: Four novel ICOS mutations included homozygous c.323_332del, homozygous c.451C>G, and compound heterozygous c.58+1G>A/c.356T>C. The predominant clinical phenotype was that of antibody deficiency associated with inflammatory complications in 4/7 patients. Six out of seven patients were treated with immunoglobulin replacement and one patient died from salmonella sepsis. All patients who were tested showed reduced IL-10 and IL-17 cytokine responses, normal IL-1β, IL6, and TNF release following LPS stimulation and highly elevated IL-12 production in response to combined LPS/IFNγ stimulation. This was associated with skewing of CD4+ T cells towards Th1 phenotype and increased expression of ICOSL on monocytes. Lastly, reduced CTLA4 expression was found in 2 patients. One patient treated with ustekinumab for pancytopenia due to granulomatous bone marrow infiltration failed to respond to this targeted therapy. Conclusions: ICOS deficiency is associated with defective T cell activation, with simultaneously enhanced stimulation of monocytes. The latter is likely to result from a lack of ICOS/ICOSL interaction which might be necessary to provide negative feedback which limits monocytes activation

GRAZ, Hauptplatz

Hauptplatz mit Erzherzog-Johann-Brunnendenkma

Immunodeficiency in Bloom’s Syndrome

Bloom’s syndrome (BS) is an autosomal recessive disease, caused by mutations in the BLM gene. This gene codes for BLM protein, which is a helicase involved in DNA repair. DNA repair is especially important for the development and maturation of the T and B cells. Since BLM is involved in DNA repair, we aimed to study if BLM deficiency affects T and B cell development and especially somatic hypermutation (SHM) and class switch recombination (CSR) processes. Clinical data of six BS patients was collected, and immunoglobulin serum levels were measured at different time points. In addition, we performed immune phenotyping of the B and T cells and analyzed the SHM and CSR in detail by analyzing IGHA and IGHG transcripts using next-generation sequencing. The serum immunoglobulin levels were relatively low, and patients had an increased number of infections. The absolute number of T, B, and NK cells were low but still in the normal range. Remarkably, all BS patients studied had a high percentage (20–80%) of CD4+ and CD8+ effector memory T cells. The process of SHM seems normal; however, the Ig subclass distribution was not normal, since the BS patients had more IGHG1 and IGHG3 transcripts. In conclusion, BS patients have low number of lymphocytes, but the immunodeficiency seems relatively mild since they have no severe or opportunistic infections. Most changes in the B cell development were seen in the CSR process; however, further studies are necessary to elucidate the exact role of BLM in CSR

Genetic heterogeneity in primary and relapsed mantle cell lymphomas : impact of recurrent CARD11 mutations

The genetic mechanisms underlying disease progression, relapse and therapy resistance in mantle cell lymphoma (MCL) remain largely unknown. Whole-exome sequencing was performed in 27 MCL samples from 13 patients, representing the largest analyzed series of consecutive biopsies obtained at diagnosis and/or relapse for this type of lymphoma. Eighteen genes were found to be recurrently mutated in these samples, including known (ATM, MEF2B and MLL2) and novel mutation targets (S1PR1 and CARD11). CARD11, a scaffold protein required for B-cell receptor (BCR)-induced NF-κB activation, was subsequently screened in an additional 173 MCL samples and mutations were observed in 5.5% of cases. Based on in vitro cell line-based experiments, overexpression of CARD11 mutants were demonstrated to confer resistance to the BCR-inhibitor ibrutinib and NF-κB-inhibitor lenalidomide. Genetic alterations acquired in the relapse samples were found to be largely non-recurrent, in line with the branched evolutionary pattern of clonal evolution observed in most cases. In summary, this study highlights the genetic heterogeneity in MCL, in particular at relapse, and provides for the first time genetic evidence of BCR/NF-κB activation in a subset of MCL

Unique DNA Repair Gene Variations and Potential Associations with the Primary Antibody Deficiency Syndromes IgAD and CVID

BACKGROUND: Despite considerable effort, the genetic factors responsible for >90% of the antibody deficiency syndromes IgAD and CVID remain elusive. To produce a functionally diverse antibody repertoire B lymphocytes undergo class switch recombination. This process is initiated by AID-catalyzed deamination of cytidine to uridine in switch region DNA. Subsequently, these residues are recognized by the uracil excision enzyme UNG2 or the mismatch repair proteins MutSalpha (MSH2/MSH6) and MutLalpha (PMS2/MLH1). Further processing by ubiquitous DNA repair factors is thought to introduce DNA breaks, ultimately leading to class switch recombination and expression of a different antibody isotype. METHODOLOGY/PRINCIPAL FINDINGS: Defects in AID and UNG2 have been shown to result in the primary immunodeficiency hyper-IgM syndrome, leading us to hypothesize that additional, potentially more subtle, DNA repair gene variations may underlie the clinically related antibody deficiencies syndromes IgAD and CVID. In a survey of twenty-seven candidate DNA metabolism genes, markers in MSH2, RAD50, and RAD52 were associated with IgAD/CVID, prompting further investigation into these pathways. Resequencing identified four rare, non-synonymous alleles associated with IgAD/CVID, two in MLH1, one in RAD50, and one in NBS1. One IgAD patient carried heterozygous non-synonymous mutations in MLH1, MSH2, and NBS1. Functional studies revealed that one of the identified mutations, a premature RAD50 stop codon (Q372X), confers increased sensitivity to ionizing radiation. CONCLUSIONS: Our results are consistent with a class switch recombination model in which AID-catalyzed uridines are processed by multiple DNA repair pathways. Genetic defects in these DNA repair pathways may contribute to IgAD and CVID