CD26-negative and CD26-positive tissue-resident fibroblasts contribute to functionally distinct CAF subpopulations in breast cancer

The origin of cancer-associated fibroblasts (CAFs) in cancer remains to be identified. Here, single-cell transcriptomics, in vivo and in vitro studies suggest that CD26+ and CD26- normal fibroblasts transform into distinct CAF subpopulations in mouse models of breast cancer

Effectiveness of a digital alcohol moderation intervention as an add-on to depression treatment for young adults: study protocol of a multicentre pragmatic randomized controlled trial

Background: Depressive disorders and problematic drinking often co-occur, also among young adults. These co-occurring conditions are associated with various negative health outcomes compared to both conditions alone. Early intervention by addressing alcohol use and depressive symptoms simultaneously in the same treatment might improve both conditions. However, evidence on the (cost-) effectiveness of digital combined depression and alcohol interventions for young adults is currently insufficient. We therefore developed an add-on digital alcohol moderation adherence-focussed guided intervention to complement treatment as usual (TAU) for depressive disorders. The digital intervention is a web-app, including 6 modules based on motivational interviewing and cognitive behavioural therapy. This study aims to evaluate the (cost-)effectiveness of a digital alcohol moderation intervention + TAU compared to TAU on alcohol and depression outcomes among young adults with co-occurring depressive disorders and problematic alcohol use.Methods: One hundred fifty-six participants, aged 18-35 years, with problematic alcohol use and a diagnosed depressive disorder will participate in a pragmatic multicentre two-arm randomized controlled trial. Problematic alcohol use is operationalised as scoring >= 5 for women and >= 8 for men on the Alcohol Use Disorder Identification Test (AUDIT). Participants will be randomized to either the experimental group (digital alcohol intervention + TAU) or control group (TAU only). Participants will be recruited at three Dutch mental health care centres and through social media. Assessments take place at baseline and after 3, 6 and 12 months post-randomization. The primary outcome is treatment response at 6-month follow-up, operationalized as a composite score that combines alcohol use and depression measures and indicates whether treatment has been successful or not. Secondary outcomes are depressive symptoms and alcohol use (i.e. number of weekly standard drinks and AUDIT score). An economic evaluation will be conducted alongside the trial.Discussion: This study evaluates the (cost-) effectiveness of an add-on digital alcohol moderation intervention for young adults who are in treatment for depressive disorders. If proven effective, the digital intervention could be implemented in mental health care and improve treatment for people with co-occurring depressive disorders and problematic alcohol use.</div

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 Alzheimer disease locus located near the gene encoding tau protein

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordAPOE ε4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ε4+ (10 352 cases and 9207 controls) and APOE ε4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ε4 status. Suggestive associations (P<1 × 10-4) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ε4+: 1250 cases and 536 controls; APOE ε4-: 718 cases and 1699 controls). Among APOE ε4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10-9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ε4+ subjects (CR1 and CLU) or APOE ε4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10-7) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P≤1.3 × 10-8), frontal cortex (P≤1.3 × 10-9) and temporal cortex (P≤1.2 × 10-11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10-6) and temporal cortex (P=2.6 × 10-6). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ε4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted

Werken aan een toekomst: Eventhands Empowert kwetsbare jongeren

Psychological problems are common amongst youth who experience problems in multiple area’s of life. Connection to community and social networks is essential in order to treat and resolve mental illness. As it o¥ ers youths the chance to experience positivity and success, improve their self image and regain perspective. To stimulate the development of this target group, youth welfare and youth mentalhealthcare sectors need each other. In cooperation lies the chance of creating better opportunities for a large group of adolescents. The EventHandsprogram, operational in Amsterdam since 2010, o¥ ers youths who experience di¼ culties in school, work or at home, the opportunity to get their lives back on track. They gain work experience within the cultural sector under professional supervision. The approach links up with the branch of positive psychology and aims to: empower and facilitate personal growth, prepare for education, labor and social participation. Initial results are promising

A Behaviorally Informed Financial Education Program for the Financially Vulnerable: Design and Effectiveness

Financially vulnerable consumers are often associated with suboptimal financial behaviors. Evaluated financial education programs so far show difficulties to effectively reach this target population. In our attempt to solve this problem, we built a behaviorally informed financial education program incorporating insights from both motivational and behavioral change theories. In a quasi-experimental field study among Dutch financially vulnerable people, we compared this program with both a control group and a traditional program group. In comparison with the control group, we found robust positive effects of the behaviorally informed program on financial skills and knowledge and self-reported financial behavior, but not on other outcomes. Additionally, we did not find evidence that the behaviorally informed program performed better than the traditional program. Finally, we discuss the findings and limitations of this study in light of the financial education literature and provide implications for policymaking and directions for future research

A behaviorally informed financial education program for the financially vulnerable : Design and effectiveness

Financially vulnerable consumers are often associated with suboptimal financial behaviors. Evaluated financial education programs so far show difficulties to effectively reach this target population. In our attempt to solve this problem, we built a behaviorally informed financial education program incorporating insights from both motivational and behavioral change theories. In a quasi-experimental field study among Dutch financially vulnerable people, we compared this program with both a control group and a traditional program group. In comparison with the control group, we found robust positive effects of the behaviorally informed program on financial skills and knowledge and self-reported financial behavior, but not on other outcomes. Additionally, we did not find evidence that the behaviorally informed program performed better than the traditional program. Finally, we discuss the findings and limitations of this study in light of the financial education literature and provide implications for policymaking and directions for future research

Data_Sheet_1_A behaviorally informed financial education program for the financially vulnerable: Design and effectiveness.pdf

Financially vulnerable consumers are often associated with suboptimal financial behaviors. Evaluated financial education programs so far show difficulties to effectively reach this target population. In our attempt to solve this problem, we built a behaviorally informed financial education program incorporating insights from both motivational and behavioral change theories. In a quasi-experimental field study among Dutch financially vulnerable people, we compared this program with both a control group and a traditional program group. In comparison with the control group, we found robust positive effects of the behaviorally informed program on financial skills and knowledge and self-reported financial behavior, but not on other outcomes. Additionally, we did not find evidence that the behaviorally informed program performed better than the traditional program. Finally, we discuss the findings and limitations of this study in light of the financial education literature and provide implications for policymaking and directions for future research.</p

Effectiviteit van de budgetcursus: Onderzoek naar de effecten van twee verschillende budgetcursussen

In Nederland is steeds meer aandacht voor het versterken van de financiële competenties van burgers. Een van de interventies die daarvoor wordt ingezet is de budgetcursus. Het betreft meestal vijf of zes lessen waar deelnemers vaardigheden leren om beter om te gaan met geld. Er is echter weinig bekend over de effectiviteit van deze cursussen. In samenwerking met Avres, Werk en Inkomen Lekstroom, de gemeente Zwolle, de Sociale Dienst Drechtsteden en Buurtteams Utrecht hebben het lectoraat Schulden en Incasso van de Hogeschool Utrecht en leerstoelgroep Urban Economics van de Wageningen Universiteit daarom de effectiviteit van twee typen budgetcursussen onderzocht: de traditionele cursus en een op gedragswetenschappelijke inzichten aangepaste cursus. Bij de traditionele budgetcursus ligt de nadruk meer op de overdracht van kennis en vaardigheden, bij de aangepaste cursus is er meer aandacht voor het handelen van de cursisten in het dagelijks leve