Interfirm Job Mobility of Two Cohorts of Young German Men 1979 - 1990: An analysis of the (West-)German Employment Statistic Register Sample concerning multivariate failure times and unobserved heterogeneity

The OECD (1993) has documented that the majority of workers in industrialised countries can look forward to finding a stable employment relationship. However new entrants into the labor force experience high turnover. Promoting institutions which support longer tenures and worker participation (or ''voice`` in the firm) utilize strategies to encourage enterprise and employee efforts in skill formation and training. The results of the OECD (1993) study show that attachments between employee and employer are more likely to endure for Japanese, French and German workers. Furthermore Germany has the highest share of young new recruits who received any formal training from their employer. In Germany, 71.5 % of young new recruits were trained at any job within 7 years after leaving school, whereas in the U.S. only 10.2 % of young new recruits were similarly trained (cf. OECD 1993, 137). It is sometimes assumed that employment protection policies have been exogenously imposed and thus probably impair efficiency. However, research on the micro-economics of labor markets has shown that employers may be interested in long-term employment relationships (cf. Levine 1991). Here, the job training model focusing on the importance of human capital investment, specifically the job shopping and matching model stressing the process of information gathering through employment experience should be mentioned. In such models employment protection legislation has not only desirable distributional effects but also help to ensure efficient outcomes. Therefore, it is important to assess the relevance of micro- economic theories empirically. This paper provides an empirical analysis of job durations in Western Germany using information from two cohorts of new entrants to the labor force documented in the (West-)German employment statistic register sample (cf. Bender and Hilzendegen 1996). The appropriate empirical technique to study job length is event history or survival analysis. In labor market research, survival analysis has primarily focused on explaining the length of unemployment spells. Application of this technique to employment is less common 1 , because huge longitudinal data sets are needed. Apart from testing hypotheses about the effect of personal characteristics and labor demand variables (e.g. firm size and industry affiliation), we will assess the influence of heterogeneity of the members of the two cohorts on their duration profile. The applied model and estimation method allow for unobserved heterogeneity and correlation between the clustered failure times of one employee as well as for right-censored spells. Our analysis is not restricted to the beginning of the working life of the employees. The individual retirement decision is affected by employment protection and early retirement regulations which differ widely between the firms. The respective data are missing in the employment statistic register, so that the retirement decision cannot be modelled explicitly

Skin dendritic cells in melanoma are key for successful checkpoint blockade therapy.

BACKGROUND: Immunotherapy with checkpoint inhibitors has shown impressive results in patients with melanoma, but still many do not benefit from this line of treatment. A lack of tumor-infiltrating T cells is a common reason for therapy failure but also a loss of intratumoral dendritic cells (DCs) has been described. METHODS: We used the transgenic tg(Grm1)EPv melanoma mouse strain that develops spontaneous, slow-growing tumors to perform immunological analysis during tumor progression. With flow cytometry, the frequencies of DCs and T cells at different tumor stages and the expression of the inhibitory molecules programmed cell death protein-1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) on T cells were analyzed. This was complemented with RNA-sequencing (RNA-seq) and real-time quantitative PCR (RT-qPCR) analysis to investigate the immune status of the tumors. To boost DC numbers and function, we administered Fms-related tyrosine 3 ligand (Flt3L) plus an adjuvant mix of polyI:C and anti-CD40. To enhance T cell function, we tested several checkpoint blockade antibodies. Immunological alterations were characterized in tumor and tumor-draining lymph nodes (LNs) by flow cytometry, CyTOF, microarray and RT-qPCR to understand how immune cells can control tumor growth. The specific role of migratory skin DCs was investigated by coculture of sorted DC subsets with melanoma-specific CD8+ T cells. RESULTS: Our study revealed that tumor progression is characterized by upregulation of checkpoint molecules and a gradual loss of the dermal conventional DC (cDC) 2 subset. Monotherapy with checkpoint blockade could not restore antitumor immunity, whereas boosting DC numbers and activation increased tumor immunogenicity. This was reflected by higher numbers of activated cDC1 and cDC2 as well as CD4+ and CD8+ T cells in treated tumors. At the same time, the DC boost approach reinforced migratory dermal DC subsets to prime gp100-specific CD8+ T cells in tumor-draining LNs that expressed PD-1/TIM-3 and produced interferon γ (IFNγ)/tumor necrosis factor α (TNFα). As a consequence, the combination of the DC boost with antibodies against PD-1 and TIM-3 released the brake from T cells, leading to improved function within the tumors and delayed tumor growth. CONCLUSIONS: Our results set forth the importance of skin DC in cancer immunotherapy, and demonstrates that restoring DC function is key to enhancing tumor immunogenicity and subsequently responsiveness to checkpoint blockade therapy

Seniority and Job Stability: A Quantile Regression Approach Using Matched Employer-Employee Data

Job mobility and employment durations can be explained by different theoretical approaches, such as job matching or human capital theory or dual labor market approaches. These models may, however, apply to different degrees at different durations in the employment spell. Standard empirical techniques, such as hazard rate analysis, cannot deal with this problem. In this paper, we apply censored quantile regression techniques to estimate employment durations of male workers in Germany. Our results give some support to the job matching model: individuals with a high risk of being bad matches exhibit higher exit rates initially, but the effect fades out over time. By contrast, the influence of human capital variables such as education and further training decreases with employment duration, which is inconsistent with the notion of increasing match-specific rents due to human capital accumulation. The results also suggest that the effects of certain labor market institutions, such as works councils, differ markedly between short-term and long-term employment, supporting the view that institutions give rise to dual labor markets

Genomic and Transcriptomic Determinants of Therapy Resistance and Immune Landscape Evolution during Anti-EGFR Treatment in Colorectal Cancer

Despite biomarker stratification, the anti-EGFR antibody cetuximab is only effective against a subgroup of colorectal cancers (CRCs). This genomic and transcriptomic analysis of the cetuximab resistance landscape in 35 RAS wild-type CRCs identified associations of NF1 and non-canonical RAS/RAF aberrations with primary resistance and validated transcriptomic CRC subtypes as non-genetic predictors of benefit. Sixty-four percent of biopsies with acquired resistance harbored no genetic resistance drivers. Most of these had switched from a cetuximab-sensitive transcriptomic subtype at baseline to a fibroblast- and growth factor-rich subtype at progression. Fibroblast-supernatant conferred cetuximab resistance in vitro, confirming a major role for non-genetic resistance through stromal remodeling. Cetuximab treatment increased cytotoxic immune infiltrates and PD-L1 and LAG3 immune checkpoint expression, potentially providing opportunities to treat cetuximab-resistant CRCs with immunotherapy

Genomic and Transcriptomic Determinants of Therapy Resistance and Immune Landscape Evolution during Anti-EGFR Treatment in Colorectal Cancer.

Despite biomarker stratification, the anti-EGFR antibody cetuximab is only effective against a subgroup of colorectal cancers (CRCs). This genomic and transcriptomic analysis of the cetuximab resistance landscape in 35 RAS wild-type CRCs identified associations of NF1 and non-canonical RAS/RAF aberrations with primary resistance and validated transcriptomic CRC subtypes as non-genetic predictors of benefit. Sixty-four percent of biopsies with acquired resistance harbored no genetic resistance drivers. Most of these had switched from a cetuximab-sensitive transcriptomic subtype at baseline to a fibroblast- and growth factor-rich subtype at progression. Fibroblast-supernatant conferred cetuximab resistance in vitro, confirming a major role for non-genetic resistance through stromal remodeling. Cetuximab treatment increased cytotoxic immune infiltrates and PD-L1 and LAG3 immune checkpoint expression, potentially providing opportunities to treat cetuximab-resistant CRCs with immunotherapy

Interfirm job mobility of two cohorts of young german men 1979 - 1990: an analysis of the (West-)German Employment Statistic Register Sample concerning multivariate failure times and unobserved heterogeneity

SIGLEAvailable from TIB Hannover: RR 6137(94) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman