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Aim Health economic evaluations conducted from a societal perspective currently do not consider inter-sectoral unit costs (UC) of the German Criminal Justice Sector.Methods UCwere calculated according to the pre-defined measurement parameters from the PECUNIA questionnaire by means of literature and internet research, or direct correspondence with the institution. If UC could not be identified, proxies were used.Results UC were calculated for police, fire brigade, vandalism, prison, police custody, simple and serious theft, minor and serious vandalism of real estate, and legal fees in court.Conclusion The lack of UC for services in the criminal justice sector in Germany makes this work important for health economic evaluations from a societal perspective. The usability of the developed UC outside of health economics, such as forensic psychiatry, emphasizes the relevance of this work.

Due to currently lacking internationally comparable measurement and valuation methods for costs and benefits of interventions in mental health care that spill over to sectors outside the health care sector, such as the education and the criminal justice system, Work Package (WP) 2of the ProgrammE in Costing, resource use measurement and outcome valuation for Use in multi-sectoral National and International health economic evaluAtions (PECUNIA, 2018-2021) focuses on the development of these methods. The first aim of WP2was to establish harmonisedservice lists and and/or resource descriptions for the six participating PECUNIA countries (Austria, Germany, Hungary, the Netherlands, Spain and United Kingdom) for mental disorders. Further, a standardized module for a multi-sectoral service and resource-use measurement (RUM) instrument was to be developed ensuring cross-country comparability and transferability. In line with the final objective of WP2, based on the identified services and their descriptions and compatible with the developed RUM instrument (Horizontal Activities 1-3, HAs1-3), standardized costing templates for criminal justice and education were to be developed in accordance with HA4 (‘Valuation’), corresponding to Deliverable 2.4. This Deliverable 2.4 report presents the activities and results related to the final objective of WP2, i.e. the development of standardized unit cost templates for the criminal justice and education sectors by the Maastricht University (Care and Public Health Research Institute) until December 2019. Suggested citation: Drost R, Evers S, Janssen L, Paulus A, Pokhilenko I, on behalf of the PECUNIA Group (2019): Standardised costing template for selected costing approaches: criminal justice and education. Deliverable D2.4: PECUNIA project. Maastricht University, Netherlands.DOI:10.5281/zenodo.4455364 For further information, please contact secretariaat-caphri@maastrichtuniversity.nl

De grote steden in ons land groeien vooral door immigratie en de aanleg van nieuwe wijken binnen de stadsgrenzen. De modieuze stelling dat yuppen met bakfietsen in de binnenstad de groei veroorzaken en de stad aantrekkelijk maken, vertekent de werkelijkheid.

FOXA1 expression correlates with the breast cancer luminal subtype and patient survival. RNA and protein analysis of a panel of breast cancer cell lines revealed that BRCA1 deficiency is associated with the downregulation of FOXA1 expression. Knockdown of BRCA1 resulted in the downregulation of FOXA1 expression and enhancement of FOXA1 promoter methylation in MCF-7 breast cancer cells, whereas the reconstitution of BRCA1 in Brca1-deficent mouse mammary epithelial cells (MMECs) promoted Foxa1 expression and methylation. These data suggest that BRCA1 suppresses FOXA1 hypermethylation and silencing. Consistently, the treatment of MMECs with the DNA methylation inhibitor 5-aza-2'-deoxycitydine induced Foxa1 mRNA expression. Furthermore, treatment with GSK126, an inhibitor of EZH2 methyltransferase activity, induced FOXA1 expression in BRCA1-deficient but not in BRCA1-reconstituted MMECs. Likewise, the depletion of EZH2 by small interfering RNA enhanced FOXA1 mRNA expression. Chromatin immunoprecipitation (ChIP) analysis demonstrated that BRCA1, EZH2, DNA methyltransferases (DNMT)1/3a/3b and H3K27me3 are recruited to the endogenous FOXA1 promoter, further supporting the hypothesis that these proteins interact to modulate FOXA1 methylation and repression. Further co-immunoprecipitation and ChIP analysis showed that both BRCA1 and DNMT3b form complexes with EZH2 but not with each other, consistent with the notion that BRCA1 binds to EZH2 and negatively regulates its methyltransferase activity. We also found that EZH2 promotes and BRCA1 impairs the deposit of the gene silencing histone mark H3K27me3 on the FOXA1 promoter. These associations were validated in a familial breast cancer patient cohort. Integrated analysis of the global gene methylation and expression profiles of a set of 33 familial breast tumours revealed that FOXA1 promoter methylation is inversely correlated with the transcriptional expression of FOXA1 and that BRCA1 mutation breast cancer is significantly associated with FOXA1 methylation and downregulation of FOXA1 expression, providing physiological evidence to our findings that FOXA1 expression is regulated by methylation and chromatin silencing and that BRCA1 maintains FOXA1 expression through suppressing FOXA1 gene methylation in breast cancer.Oncogene advance online publication, 22 December 2014; doi:10.1038/onc.2014.421., published_or_final_version

PALB2 interacts with BRCA1 and BRCA2 in supercomplexes involved in DNA repair via homologous recombination. Heterozygous germline mutations in PALB2 confer a moderate risk of breast cancer, while biallelic PALB2 mutations are linked to a severe form of Fanconi anaemia characterized by early childhood solid tumours and severe chromosomal instability. In contrast to BRCA1- or BRCA2-associated cancers, breast tumours in heterozygous PALB2 mutation carriers do not show loss of the wild-type allele, suggesting PALB2 might be haploinsufficient for tumour suppression. To study the role of PALB2 in development and tumourigenesis, we have generated Palb2(GT) mouse mutants using a gene trap approach. Whereas Palb2(GT/GT) homozygous mutant embryos died at mid-gestation due to massive apoptosis, Palb2(GT/+) heterozygous mice were viable and did not show any obvious abnormalities. Deletion of p53 alleviated the phenotype of Palb2(GT/GT) embryos, but did not rescue embryonic lethality. In addition, loss of p53 did not significantly collaborate with Palb2 heterozygosity in tumourigenesis in heterozygous or homozygous p53 knockout mice. Tumours arising in Palb2(GT/+); p53(+/-) or Palb2(GT/+); p53(-/-) compound mutant mice retained the wild-type Palb2 allele and did not display increased genomic instability. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.