Predictors of return to work for people on sick leave with depression, anxiety and stress: secondary analysis from a randomized controlled trial.

PURPOSE: Knowledge about predictors of return to work (RTW) in people on sick leave with common mental disorders (CMDs) may inform the development of effective vocational rehabilitation interventions for this target group. In this study, we investigated predictors of RTW at 6 and 12 months in people on sick leave with depression, anxiety disorders or stress-related disorders. METHODS: We have performed a secondary analysis, utilizing data from two RCTs that evaluated the efficacy of an integrated health care and vocational rehabilitation intervention. Data were obtained from mental health assessments, questionnaires and registers. Using Cox regression analysis, the relationship between baseline variables and RTW was analysed at 6 and 12 months after randomization within the group of CMD as a whole and within the subgroups of depression, anxiety and stress-related disorders. RESULTS: Symptom burden and employment status at baseline predicted RTW in the CMD group (n = 1245) and in the three diagnostic subgroups at both time points. RTW self-efficacy predicted RTW in the depression group but not in the anxiety or stress subgroups. CONCLUSION: Many predictors of RTW were similar over time and, to some extent, across the CMD subgroups. Findings highlight the need not only to take health-related and psychological factors into account when developing vocational rehabilitation interventions but also to consider workplace strategies and options for support.

Integrated mental healthcare and vocational rehabilitation for people on sick leave with stress-related disorders: 24-month follow-up of the randomized IBBIS trial.

OBJECTIVES: Integrating vocational rehabilitation and mental healthcare has shown effects on vocational outcomes during sick leave with common mental disorders. In a previous paper, we showed that a Danish integrated healthcare and vocational rehabilitation intervention (INT) had a surprisingly negative impact on vocational outcomes compared to service as usual (SAU) at 6- and 12-month follow-up. That was also the case with a mental healthcare intervention (MHC) tested in the same study. This article reports the 24-month follow-up results of that same study. METHOD: A randomized, parallel-group, three-arm, multi-centre superiority trial was conducted to test the effectiveness of INT and MHC compared to SAU. RESULTS: In total, 631 persons were randomized. Contrary to our hypothesis, SAU showed faster return to work than both INT [hazard rate (HR) 1.39, P=0.0027] and MHC (HR 1.30, P=0.013) at 24-month follow-up. Overall, no differences were observed regarding mental health and functional level. Compared to SAU, we observed some health benefits of MHC, but not INT, at 6-month follow-up but not thereafter, and lower rates of employment at all follow-ups. Since implementation problems might explain the results of INT, we cannot conclude that INT is no better that SAU. The MHC intervention was implemented with good fidelity and did not improve return to work. CONCLUSION: This trial does not support the hypothesis that INT lead to faster return to work. However, implementation failure may explain the negative results.

Integrated Mental Healthcare and Vocational Rehabilitation for People on Sick Leave with Anxiety or Depression: 24-Month Follow-up of the Randomized IBBIS Trial.

Integration of vocational rehabilitation and mental healthcare has shown some effect on work participation at 1-year follow-up after sick leave with depression and anxiety. We aimed to study the effect on work and health outcomes at 2-year follow-up, why we performed a randomized trial was conducted to study the effectiveness of integrated intervention (INT) compared to service as usual (SAU) and best practice mental healthcare (MHC). We included 631 participants, and at 24-month follow-up, we detected no differences in effect between INT and SAU. Compared to MHC, INT showed faster return-to-work (RTW) rates (p = 0.044) and a higher number of weeks in work (p = 0.024). No symptom differences were observed between the groups at 24 months. In conclusion, compared to SAU, INT was associated with a slightly higher work rate reaching borderline statistical significance at 12-month follow-up and lower stress levels at 6-month follow-up. The disappearance of relative effect between 12 and 24 months may be explained by the fact that the intervention lasted less than 12 months or by delayed spontaneous remission in the SAU group after 12 months. Despite the lack of effect at long-term follow-up, INT still performed slightly better than SAU overall. Moderate implementation difficulties, may partly explain the absence of the hypothesized effect. Integrated intervention, as implemented in this trial, showed some positive effects on mid-term vocational status and short-term stress symptom levels. However, these effects were not sustained beyond the duration of the intervention.

Somatic mutations reveal complex metastatic seeding from multifocal primary prostate cancer.

Primary prostate cancer shows a striking intraorgan molecular heterogeneity, with multiple spatially separated malignant foci in the majority of patients. Metastatic prostate cancer, however, typically reveals more homogenous molecular profiles, suggesting a monoclonal origin of the metastatic lesions. Longitudinal mutational spectra, comparing multiple primary lesions with metastases from the same patients remain poorly defined. We have here analyzed somatic mutations in multisampled, spatio-temporal biobanked lesions (38 samples from primary foci and 1 sample from each of 8 metastases from seven prostate cancer patients) applying a custom-designed panel targeting 68 prostate cancer relevant genes. The metastatic samples were taken at time of primary surgery and up to 7 years later, and sampling included circulating tumor DNA in plasma or solid metastatic tissue samples. A total of 282 somatic mutations were detected, with a range of 0 to 25 mutations per sample. Although seven samples had solely private mutations, the remaining 39 samples had both private and shared mutations. Seventy-four percent of mutations in metastases were not found in any primary samples, and vice versa, 96% of mutations in primary cancers were not found in any metastatic samples. However, for three patients, shared mutations were found suggesting the focus of origin, including mutations in AKT1, FOXA1, HOXB13, RB1 and TP53. In conclusion, the spatio-temporal heterogeneous nature of multifocal disease is emphasized in our study, and underlines the importance of testing a recent sample in genomics-based precision medicine for metastatic prostate cancer.

Integrating vocational rehabilitation and mental healthcare to improve the return-to-work process for people on sick leave with stress-related disorders: results from a randomized trial.

OBJECTIVE: Stress-related disorders are common, associated with substantial individual suffering, and place a large economic burden on society. While treatment appears to be able to reduce symptoms, evidence of interventions to improve vocational outcomes is flimsy. Lack of integration of vocational rehabilitation and healthcare services has been suspected to be a major potential barrier in return-to-work (RTW) processes; therefore, we aimed to test the effectiveness of such integration. METHODS: We randomized participants who were on sick leave for ≥ 4 weeks with a stress-related disorder. They were allocated to (i) service as usual (SAU), (ii) improved mental healthcare (MHC), or (iii) integrated interventions (INT). The primary outcome was RTW rates measured at 12 months. Secondary outcome were RTW rates measured at 6 months, proportion in work at 12 months, and levels of stress, anxiety, depression, and functioning at 6 months. RESULTS: We included 666 participants. On the primary outcome and almost all other vocational outcomes, SAU was superior to both INT and MHC. MHC and INT did not differ on any vocational outcome. On several symptom scales, MHC showed lower values than SAU, whilst INT did not differ from the two other groups. CONCLUSION: Both the INT and the MHC intervention lowered RTW rates compared with SAU, and thereby yielded a worse outcome. However, the MHC group showed a tendency towards having lower symptom levels compared with those in the SAU group; accordingly, the SAU group is not unequivocally superior. MHC and INT showed no general differences.

Integrating vocational rehabilitation and mental healthcare to improve the return-to-work process for people on sick leave with depression or anxiety: results from a three-arm, parallel randomised trial.

OBJECTIVE: The aim of this study was to investigate an integrated mental healthcare and vocational rehabilitation intervention to improve and hasten the process of return-to-work of people on sick leave with anxiety and depression. METHODS: In this three-arm, randomised trial, participants were assigned to (1) integrated intervention (INT), (2) improved mental healthcare (MHC) or (3) service as usual (SAU). The primary outcome was time to return-to-work measured at 12-month follow-up. The secondary outcomes were time to return-to-work measured at 6-month follow-up; levels of anxiety, depression, stress symptoms, and social and occupational functioning at 6 months; and return-to-work measured as proportion in work at 12 months. RESULTS: 631 individuals were randomised. INT yielded a higher proportion in work compared with both MHC (56.2% vs 43.7%, p=0.012) and SAU (56.2% vs 45%, p=0.029) at 12-month follow-up. We found no differences in return-to-work in terms of sick leave duration at either 6-month or 12-month follow-up, with the latter being the primary outcome. No differences in anxiety, depression or functioning between INT, MHC and SAU were identified, but INT and MHC showed lower scores on Cohen's Perceived Stress Scale compared with SAU at 12-month follow-up. CONCLUSIONS: Although INT did not hasten the process of return-to-work, it yielded better outcome with regard to proportion in work compared with MHC and SAU. The findings suggest that INT compared with SAU is associated with a few, minor health benefits. Overall, INT yielded slightly better vocational and health outcomes, but the clinical significance of the health advantage is questionable. TRIAL REGISTRATION NUMBER: NCT02872051.

Assessing measurement equivalence of the Danish and Dutch Four-Dimensional Symptom Questionnaire using differential item and test functioning analysis.

Aims: The Dutch Four-Dimensional Symptom Questionnaire (4DSQ) measures distress, depression, anxiety and somatisation, facilitating the distinction between stress-related problems and psychiatric disorder in primary and occupational health care. The aim of the study was to examine the measurement equivalence across the Danish and Dutch 4DSQ. Methods: Danish 4DSQ data were obtained from a cohort of Danish citizens on sick leave for mental-health problems. Dutch 4DSQ data were obtained from a cohort of Dutch employees on sick leave and a cohort of general practice attenders suspected of having mental-health problems. The study samples were matched on age and sex. The 4DSQ scales were assessed for essential unidimensionality using confirmatory factor analysis. Measurement equivalence of the 4DSQ across the groups was assessed using differential item and test functioning (DIF and DTF) analysis. Results: The study groups each consisted of 1363 people (63% female, Mage=42 years). The 4DSQ scales proved essentially unidimensional. DIF was detected in 20 items. In terms of Cohen's effect size, DIF was mostly small or moderate. In terms of effect size, the mean effect on the scale score (DTF) was negligible. Nevertheless, it is recommended to adjust some of the cut-off points for two Danish 4DSQ scales to retain the meaning of these cut-off points in Dutch respondents. Conclusions: The Danish version of the 4DSQ measures the same constructs as the original Dutch questionnaire. Twenty items functioned differently in Danish respondents than in Dutch respondents, but this had only a small impact on the scale scores.

Frequent copy number gains of SLC2A3 and ETV1 in testicular embryonal carcinomas.

Testicular germ cell tumours (TGCTs) appear as different histological subtypes or mixtures of these. They show similar, multiple DNA copy number changes, where gain of 12p is pathognomonic. However, few high-resolution analyses have been performed and focal DNA copy number changes with corresponding candidate target genes remain poorly described for individual subtypes. We present the first high-resolution DNA copy number aberration (CNA) analysis on the subtype embryonal carcinomas (ECs), including 13 primary ECs and 5 EC cell lines. We identified recurrent gains and losses and allele-specific CNAs. Within these regions, we nominate 30 genes that may be of interest to the EC subtype. By in silico analysis of data from 150 TGCTs from The Cancer Genome Atlas (TCGA), we further investigated CNAs, RNA expression, somatic mutations and fusion transcripts of these genes. Among primary ECs, ploidy ranged between 2.3 and 5.0, and the most common aberrations were DNA copy number gains at chromosome (arm) 7, 8, 12p, and 17, losses at 4, 10, 11, and 18, replicating known TGCT genome characteristics. Gain of whole or parts of 12p was found in all samples, including a highly amplified 100 kbp segment at 12p13.31, containing SLC2A3. Gain at 7p21, encompassing ETV1, was the second most frequent aberration. In conclusion, we present novel CNAs and the genes located within these regions, where the copy number gain of SLC2A3 and ETV1 are of interest, and which copy number levels also correlate with expression in TGCTs.

ScaR-a tool for sensitive detection of known fusion transcripts: establishing prevalence of fusions in testicular germ cell tumors.

Bioinformatics tools for fusion transcript detection from RNA-sequencing data are in general developed for identification of novel fusions, which demands a high number of supporting reads and strict filters to avoid false discoveries. As our knowledge of bona fide fusion genes becomes more saturated, there is a need to establish their prevalence with high sensitivity. We present ScaR, a tool that uses a supervised scaffold realignment approach for sensitive fusion detection in RNA-seq data. ScaR detects a set of 130 synthetic fusion transcripts from simulated data at a higher sensitivity compared to established fusion finders. Applied to fusion transcripts potentially involved in testicular germ cell tumors (TGCTs), ScaR detects the fusions RCC1-ABHD12B and CLEC6A-CLEC4D in 9% and 28% of 150 TGCTs, respectively. The fusions were not detected in any of 198 normal testis tissues. Thus, we demonstrate high prevalence of RCC1-ABHD12B and CLEC6A-CLEC4D in TGCTs, and their cancer specific features. Further, we find that RCC1-ABHD12B and CLEC6A-CLEC4D are predominantly expressed in the seminoma and embryonal carcinoma histological subtypes of TGCTs, respectively. In conclusion, ScaR is useful for establishing the frequency of known and validated fusion transcripts in larger data sets and detecting clinically relevant fusion transcripts with high sensitivity.

Interfocal heterogeneity challenges the clinical usefulness of molecular classification of primary prostate cancer.

Prostate cancer is a highly heterogeneous disease and typically multiple distinct cancer foci are present at primary diagnosis. Molecular classification of prostate cancer can potentially aid the precision of diagnosis and treatment. A promising genomic classifier was published by The Cancer Genome Atlas (TCGA), successfully classifying 74% of primary prostate cancers into seven groups based on one cancer sample per patient. Here, we explore the clinical usefulness of this classification by testing the classifier's performance in a multifocal context. We analyzed 106 cancer samples from 85 distinct cancer foci within 39 patients. By somatic mutation data from whole-exome sequencing and targeted qualitative and quantitative gene expression assays, 31% of the patients were uniquely classified into one of the seven TCGA classes. Further, different samples from the same focus had conflicting classification in 12% of the foci. In conclusion, the level of both intra- and interfocal heterogeneity is extensive and must be taken into consideration in the development of clinically useful molecular classification of primary prostate cancer.

Transcriptional and functional consequences of TP53 splice mutations in colorectal cancer.

TP53 mutations are common in colorectal cancer (CRC). Most TP53 sequencing studies have been restricted to coding regions, but recent studies have revealed that splice mutations can generate transcript variants with distinct tumorigenic and prognostic properties. Here, we performed unrestricted sequencing of all coding sequences and splice regions of TP53 in a single-hospital series of 401 primary CRCs. TP53 splice mutations were detected in 4% of the cases (N = 16), considerably more frequent than reported in major databases, and they were mutually exclusive to exon mutations. RNA sequencing revealed high-level expression of aberrant transcript variants in the majority of splice mutated tumors (75%). Most variants were predicted to produce truncated TP53 proteins, including one sample expressing the potentially oncogenic and druggable p53ψ isoform. Despite heterogeneous transcript structures, downstream transcriptional profiling revealed that TP53 splice mutations had similar effects on TP53 target gene expression and pathway activity as exonic mutations. Intriguingly, TP53 splice mutations were associated with worse 5-year relapse-free survival in stage II disease, compared to both TP53 wild-type and exon mutations (P = 0.007). These data highlight the importance of including splice regions when examining the biological and clinical consequences of TP53 mutations in CRC.

Multifocal Primary Prostate Cancer Exhibits High Degree of Genomic Heterogeneity.

BACKGROUND: Most primary prostate cancers are multifocal with individual tumors harboring different aggressiveness; however, the genomic heterogeneity among these tumors is poorly understood. OBJECTIVE: To better understand the biological basis for clinical variability among different lesions, we sought to comprehensively characterize the heterogeneity of somatic gene mutations in multifocal prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: High-coverage whole-exome sequencing of 153 frozen tissue samples, taken from two to three distinct tumor foci and one non-cancerous area from each of 41 patients, covering a total of 89 tumor foci. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: State-of-the-art bioinformatics tools for mutation calling and copy number determination from whole-exome sequencing data. RESULTS AND LIMITATIONS: We found a very high degree of interfocal heterogeneity among tumors, that is, 76% of pairwise-compared tumor foci from the same prostatectomy specimen had no point mutations in common and DNA copy number changes were rarely shared across cancer foci. The few point mutations shared across tumor foci were seldom in cancer-critical genes. CONCLUSIONS: In this first large genomic heterogeneity study of primary prostate cancer, we observe that different tumor foci within the same patient are genetically distinct, only rarely sharing any somatic gene mutations, including those in cancer driver genes. This heterogeneity affects how genomics-based management of prostate cancer can be implemented, as information from all tumor foci is necessary to draw valid conclusions about the cancer's genomic alterations. PATIENT SUMMARY: Most primary prostate cancers consist of multiple tumors within the same organ, but little is known about their relationships. We have compared the sets of gene mutations among such tumors and found that they only exceptionally have any in common. This will influence treatment decisions in the future as each tumor's mutations will render it unique and have to be considered to gain the best treatment results.

Structural Alterations Driving Castration-Resistant Prostate Cancer Revealed by Linked-Read Genome Sequencing.

Nearly all prostate cancer deaths are from metastatic castration-resistant prostate cancer (mCRPC), but there have been few whole-genome sequencing (WGS) studies of this disease state. We performed linked-read WGS on 23 mCRPC biopsy specimens and analyzed cell-free DNA sequencing data from 86 patients with mCRPC. In addition to frequent rearrangements affecting known prostate cancer genes, we observed complex rearrangements of the AR locus in most cases. Unexpectedly, these rearrangements include highly recurrent tandem duplications involving an upstream enhancer of AR in 70%-87% of cases compared with <2% of primary prostate cancers. A subset of cases displayed AR or MYC enhancer duplication in the context of a genome-wide tandem duplicator phenotype associated with CDK12 inactivation. Our findings highlight the complex genomic structure of mCRPC, nominate alterations that may inform prostate cancer treatment, and suggest that additional recurrent events in the non-coding mCRPC genome remain to be discovered.

CRABP1, C1QL1 and LCN2 are biomarkers of differentiated thyroid carcinoma, and predict extrathyroidal extension.

BACKGROUND: The prognostic variability of thyroid carcinomas has led to the search for accurate biomarkers at the molecular level. Follicular thyroid carcinoma (FTC) is a typical example of differentiated thyroid carcinomas (DTC) in which challenges are faced in the differential diagnosis. METHODS: We used high-throughput paired-end RNA sequencing technology to study four cases of FTC with different degree of capsular invasion: two minimally invasive (mFTC) and two widely invasive FTC (wFTC). We searched by genes differentially expressed between mFTC and wFTC, in an attempt to find biomarkers of thyroid cancer diagnosis and/or progression. Selected biomarkers were validated by real-time quantitative PCR in 137 frozen thyroid samples and in an independent dataset (TCGA), evaluating the diagnostic and the prognostic performance of the candidate biomarkers. RESULTS: We identified 17 genes significantly differentially expressed between mFTC and wFTC. C1QL1, LCN2, CRABP1 and CILP were differentially expressed in DTC in comparison with normal thyroid tissues. LCN2 and CRABP1 were also differentially expressed in DTC when compared with follicular thyroid adenoma. Additionally, overexpression of LCN2 and C1QL1 were found to be independent predictors of extrathyroidal extension in DTC. CONCLUSIONS: We conclude that the underexpression of CRABP1 and the overexpression of LCN2 may be useful diagnostic biomarkers in thyroid tumours with questionable malignity, and the overexpression of LCN2 and C1QL1 may be useful for prognostic purposes.

Integrated mental health care and vocational rehabilitation to improve return to work rates for people on sick leave because of exhaustion disorder, adjustment disorder, and distress (the Danish IBBIS trial): study protocol for a randomized controlled trial.

BACKGROUND: Common mental disorders are important contributors to the global burden of disease and cause negative effects on both the individual and society. Stress-related disorders influence the individual's workability and cause early retirement pensions in Denmark. There is no clear evidence that mental health care alone will provide sufficient support for vocational recovery for this group. Integrated vocational and health care services have shown good effects on return to work in other similar welfare contexts. The purpose of the Danish IBBIS (Integreret Behandlings- og BeskæftigelsesIndsats til Sygemeldte) study is to examine the efficacy of (1) a stepped mental health care intervention with individual stress coaching and/or group-based MBSR and (2) an integrated stepped mental health care with individual stress coaching and/or group-based MBSR and vocational rehabilitation intervention for people on sick leave because of exhaustion disorder, adjustment disorder or distress in Denmark. METHOD/DESIGN: This three-armed, parallel-group, randomized superiority trial is set up to investigate the effectiveness of a stepped mental health care intervention and an integrated mental health care and vocational rehabilitation intervention for people on sick leave because of exhaustion disorder, adjustment disorder or distress in Denmark. The trial has an investigator-initiated multicenter design. Six hundred and three patients will be recruited from Danish vocational rehabilitation centers in four municipalities and randomly assigned into three groups: (1) IBBIS mental health care integrated with IBBIS vocational rehabilitation, (2) IBBIS mental health care and standard vocational rehabilitation, and (3) standard mental health care and standard vocational rehabilitation. The primary outcome is register-based return to work at 12 months. The secondary outcome measures are self-assessed level of depression (BDI), anxiety (BAI), distress symptoms (4DSQ), work- and social functioning (WSAS), and register-based recurrent sickness absence. DISCUSSION: This study will contribute with knowledge on the consequence of the current organizational separation of health care interventions and vocational rehabilitation regarding the individual's process of returning to work after sick leave because of exhaustion disorder, adjustment disorder or distress. If the effect on return to work, symptom level, and recurrent sick leave is different in the intervention groups, this study can contribute with new knowledge on shared care models and the potential for preventing deterioration in stress symptoms, prolonged sick leave, and recurrent sick leave. TRIAL REGISTRATION: ClinicalTrials.gov, registration number: NCT02885519 . Retrospectively registered on 15 August 2016). Participants have been included in the IBBIS trial for distress, adjustment disorder and exhaustion disorder since April 2016.

Integrated mental health care and vocational rehabilitation to improve return to work rates for people on sick leave because of depression and anxiety (the Danish IBBIS trial): study protocol for a randomized controlled trial.

BACKGROUND: Depression and anxiety are among the largest contributors to the global burden of disease and have negative effects on both the individual and society. Depression and anxiety are very likely to influence the individual's work ability, and up to 40% of the people on sick leave in Denmark have depression and/or anxiety. There is no clear evidence that treatment alone will provide sufficient support for vocational recovery in this group. Integrated vocational and health care services have shown good effects on return to work in other, similar welfare contexts. The purpose of the IBBIS (Integrated Mental Health Care and Vocational Rehabilitation to Individuals on Sick Leave Due to Anxiety and Depression) interventions is to improve and hasten the process of return to employment for people in Denmark on sick leave because of depression and anxiety. METHODS/DESIGN: This three-arm, parallel-group, randomized superiority trial has been set up to investigate the effectiveness of the IBBIS mental health care intervention and the integrated IBBIS mental health care and IBBIS vocational rehabilitation intervention for people on sick leave because of depression and/or anxiety in Denmark. The trial has an investigator-initiated multicenter design. A total of 603 patients will be recruited from Danish job centers in 4 municipalities and randomly assigned to one of 3 groups: (1) IBBIS mental health care integrated with IBBIS vocational rehabilitation, (2) IBBIS mental health care and standard vocational rehabilitation, and (3) standard mental health care and standard vocational rehabilitation. The primary outcome is register-based return to work at 12 months. The secondary outcome measures are self-assessed level of depression (Beck Depression Inventory II), anxiety (Beck Anxiety Inventory), stress symptoms (Four-Dimensional Symptom Questionnaire), work and social functioning (Work and Social Adjustment Scale), and register-based recurrent sickness absence. DISCUSSION: This study will provide new knowledge on vocational recovery, integrated vocational and health care interventions, and prevention of recurrent sickness absence among people with depression and anxiety. If the effect on return to work is different in the intervention groups, this study can contribute to current knowledge on shared care models for health care and vocational rehabilitation services. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02872051 . Retrospectively registered on 15 August 2016.

[Gerontologically oriented study programs in Germany : Critical review]. / Gerontologisch orientierte Studiengänge in Deutschland : Kritische Bestandsaufnahme.

The objective of this article is a state-of-the-art analysis and critical reflection of the status quo of gerontologically oriented study programs in higher education in Germany. The major impulse for writing this article was provided by the newly established working group "Gerontological Education", which was inaugurated at the joint annual conference of sections III and IV of the German Society of Gerontology and Geriatrics in Mannheim in 2015. A systematic review of gerontological study programs shows that the number of such programs has increased in Germany over the past decade. At the same time there has been a dynamic development across the country whereby well-established programs were closed and new ones were initiated. New study programs were primarily initiated at universities of applied sciences and private universities. A tendency away from explicit gerontology programs towards other academic disciplines (e.g. sociology, social work, psychology, sports, health and rehabilitation sciences) in combination with gerontological contents can be observed. These degree programs are rooted in their respective disciplines and focus primarily on health and social issues. Given the heterogeneity of study programs the working group "Gerontological Education" could become a new forum for leaders of such programs, students, alumni and employers of gerontologists for critical reflection and further development of gerontological quality benchmarks.

Novel transcription-induced fusion RNAs in prostate cancer.

Prostate cancer is a clinically and pathologically heterogeneous disease with a broad spectrum of molecular abnormalities in the genome and transcriptome. One key feature is the involvement of chromosomal rearrangements creating fusion genes. Recent RNA-sequencing technology has uncovered that fusions which are not caused by chromosomal rearrangements, but rather meditated at transcription level, are common in both healthy and diseased cells. Such fusion transcripts have been proven highly associated with prostate cancer development and progression. To discover novel fusion transcripts, we analyzed RNA sequencing data from 44 primary prostate tumors and matched benign tissues from The Cancer Genome Atlas. Twenty-one high-confident candidates were significantly enriched in malignant vs. benign samples. Thirteen of the candidates have not previously been described in prostate cancer, and among them, five long intergenic non-coding RNAs are involved as fusion partners. Their expressions were validated in 50 additional prostate tumor samples and seven prostate cancer cell lines. For four fusion transcripts, we found a positive correlation between their expression and the expression of the 3' partner gene. Among these, differential exon usage and qRT-PCR analyses in particular support that SLC45A3-ELK4 is mediated by an RNA polymerase read-through mechanism.

chimeraviz: a tool for visualizing chimeric RNA.

SUMMARY: Advances in high-throughput RNA sequencing have enabled more efficient detection of fusion transcripts, but the technology and associated software used for fusion detection from sequencing data often yield a high false discovery rate. Good prioritization of the results is important, and this can be helped by a visualization framework that automatically integrates RNA data with known genomic features. Here we present chimeraviz , a Bioconductor package that automates the creation of chimeric RNA visualizations. The package supports input from nine different fusion-finder tools: deFuse, EricScript, InFusion, JAFFA, FusionCatcher, FusionMap, PRADA, SOAPfuse and STAR-FUSION. AVAILABILITY AND IMPLEMENTATION: chimeraviz is an R package available via Bioconductor ( https://bioconductor.org/packages/release/bioc/html/chimeraviz.html ) under Artistic-2.0. Source code and support is available at GitHub ( https://github.com/stianlagstad/chimeraviz ). CONTACT: rolf.i.skotheim@rr-research.no. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Identification of Novel Fusion Genes in Testicular Germ Cell Tumors.

Testicular germ cell tumors (TGCT) are the most frequently diagnosed solid tumors in young men ages 15 to 44 years. Embryonal carcinomas (EC) comprise a subset of TGCTs that exhibit pluripotent characteristics similar to embryonic stem (ES) cells, but the genetic drivers underlying malignant transformation of ECs are unknown. To elucidate the abnormal genetic events potentially contributing to TGCT malignancy, such as the existence of fusion genes or aberrant fusion transcript expression, we performed RNA sequencing of EC cell lines and their nonmalignant ES cell line counterparts. We identified eight novel fusion transcripts and one gene with alternative promoter usage, ETV6. Four out of nine transcripts were found recurrently expressed in an extended panel of primary TGCTs and additional EC cell lines, but not in normal parenchyma of the testis, implying tumor-specific expression. Two of the recurrent transcripts involved an intrachromosomal fusion between RCC1 and HENMT1 located 80 Mbp apart and an interchromosomal fusion between RCC1 and ABHD12B. RCC1-ABHD12B and the ETV6 transcript variant were found to be preferentially expressed in the more undifferentiated TGCT subtypes. In vitro differentiation of the NTERA2 EC cell line resulted in significantly reduced expression of both fusion transcripts involving RCC1 and the ETV6 transcript variant, indicating that they are markers of pluripotency in a malignant setting. In conclusion, we identified eight novel fusion transcripts that, to our knowledge, are the first fusion genes described in TGCT and may therefore potentially serve as genomic biomarkers of malignant progression.