A polymorphism in the base excision repair gene PARP2 is associated with differential prognosis by chemotherapy among postmenopausal breast cancer patients.

BACKGROUND: Personalized therapy considering clinical and genetic patient characteristics will further improve breast cancer survival. Two widely used treatments, chemotherapy and radiotherapy, can induce oxidative DNA damage and, if not repaired, cell death. Since base excision repair (BER) activity is specific for oxidative DNA damage, we hypothesized that germline genetic variation in this pathway will affect breast cancer-specific survival depending on treatment. METHODS: We assessed in 1,408 postmenopausal breast cancer patients from the German MARIE study whether cancer specific survival after adjuvant chemotherapy, anthracycline chemotherapy, and radiotherapy is modulated by 127 Single Nucleotide Polymorphisms (SNPs) in 21 BER genes. For SNPs with interaction terms showing p<0.1 (likelihood ratio test) using multivariable Cox proportional hazard analyses, replication in 6,392 patients from nine studies of the Breast Cancer Association Consortium (BCAC) was performed. RESULTS: rs878156 in PARP2 showed a differential effect by chemotherapy (p=0.093) and was replicated in BCAC studies (p=0.009; combined analysis p=0.002). Compared to non-carriers, carriers of the variant G allele (minor allele frequency=0.07) showed better survival after chemotherapy (combined allelic hazard ratio (HR)=0.75, 95% 0.53-1.07) and poorer survival when not treated with chemotherapy (HR=1.42, 95% 1.08-1.85). A similar effect modification by rs878156 was observed for anthracycline-based chemotherapy in both MARIE and BCAC, with improved survival in carriers (combined allelic HR=0.73, 95% CI 0.40-1.32). None of the SNPs showed significant differential effects by radiotherapy. CONCLUSIONS: Our data suggest for the first time that a SNP in PARP2, rs878156, may together with other genetic variants modulate cancer specific survival in breast cancer patients depending on chemotherapy. These germline SNPs could contribute towards the design of predictive tests for breast cancer patients

The Neuroscience Information Framework: A Data and Knowledge Environment for Neuroscience

With support from the Institutes and Centers forming the NIH Blueprint for Neuroscience Research, we have designed and implemented a new initiative for integrating access to and use of Web-based neuroscience resources: the Neuroscience Information Framework. The Framework arises from the expressed need of the neuroscience community for neuroinformatic tools and resources to aid scientific inquiry, builds upon prior development of neuroinformatics by the Human Brain Project and others, and directly derives from the Society for Neuroscience’s Neuroscience Database Gateway. Partnered with the Society, its Neuroinformatics Committee, and volunteer consultant-collaborators, our multi-site consortium has developed: (1) a comprehensive, dynamic, inventory of Web-accessible neuroscience resources, (2) an extended and integrated terminology describing resources and contents, and (3) a framework accepting and aiding concept-based queries. Evolving instantiations of the Framework may be viewed at http://nif.nih.gov, http://neurogateway.org, and other sites as they come on line

Bcl-2 protein family: Implications in vascular apoptosis and atherosclerosis

Apoptosis has been recognized as a central component in the pathogenesis of atherosclerosis, in addition to the other human pathologies such as cancer and diabetes. The pathophysiology of atherosclerosis is complex, involving both apoptosis and proliferation at different phases of its progression. Oxidative modification of lipids and inflammation differentially regulate the apoptotic and proliferative responses of vascular cells during progression of the atherosclerotic lesion. Bcl-2 proteins act as the major regulators of extrinsic and intrinsic apoptosis signalling pathways and more recently it has become evident that they mediate the apoptotic response of vascular cells in response to oxidation and inflammation either in a provocative or an inhibitory mode of action. Here we address Bcl-2 proteins as major therapeutic targets for the treatment of atherosclerosis and underscore the need for the novel preventive and therapeutic interventions against atherosclerosis, which should be designed in the light of molecular mechanisms regulating apoptosis of vascular cells in atherosclerotic lesions

Norwegian child welfare workers' perceptions of emergency placements

Emergency placements in child welfare services have increased during the last 10 years in Norway. At the time of placement, some of these children have been in the child welfare system for several years. Based on qualitative interviews, our study explores Norwegian child welfare workers' perceptions of long‐term cases resulting in emergency placements. The participants reported that they felt they had intervened too late, as it took them too long to understand the severity of the situation. This occurred mainly due to three factors: (a) The work had mainly been based on the parents' premises; (b) having too much distance to the child, as they talked too little with the child, too late in the process; (c) an experience of lacking methodological skills needed and sufficient opportunities to conduct proper observations and assessments; (d) supportive measures were tried for too long, and these measures were not properly evaluated. Giving other professionals' assessments considerable weight in the decision‐making process, and the use of legal language rather than independent, professional assessments, can be seen as another way of distancing themselves from both the family and the decisions being made.Norwegian child welfare workers' perceptions of emergency placementsacceptedVersionPublisher embargo until July 202

Psychosocial predictors of eating habits among adults in their mid-30s: The Oslo Youth Study follow-up 1991–1999

BACKGROUND: The predictive value of the psychosocial constructs of Theory of Planned Behaviour (TPB) on subsequent dietary habits has not been previously investigated in a multivariate approach that includes demographic factors and past dietary behaviour among adults. The aim of this study was to investigate to what extent TPB constructs, including intention, attitudes, subjective norms, perceived behavioural control, and perceived social norms, measured at age 25 predicted four eating behaviours (intake of fruits and vegetables, whole grains, total fat and added sugar) eight years later. METHODS: Two hundred and forty men and 279 women that participated in the Oslo Youth Study were followed from 1991 to 1999 (mean age 25 and 33 years, respectively). Questionnaires at baseline (1991) included the constructs of the TPB and dietary habits, and at follow-up (1999) questionnaires included demographic factors and diet. For the assessment of diet, a food frequency questionnaire (FFQ) with a few food items was used at baseline while an extensive semi-quantitative FFQ was used at follow-up. RESULTS: Among men, attitudes, subjective norms and previous eating behaviour were significant predictors of fruit and vegetable intake, while education and past eating behaviour were predictive of whole grain intake in multivariate analyses predicting dietary intake at follow-up. For women, perceived behavioural control, perceived social norms and past behaviour were predictive of fruit and vegetable intake, while subjective norms, education and past eating behaviour were predictive of whole grain intake. For total fat intake, intention was predictive for men and perceived behavioural control for women. Household income and past consumption of sugar-rich foods were significant predictors of added sugar intake among men, while past intake of sugar-rich foods was a significant predictor of added sugar intake among women. CONCLUSION: After adjusting for potential confounding factors, all psychosocial factors assessed among young adults appeared predictive of one or more eating behaviours reported eight years later. Results point to the influence of psychosocial factors on future eating behaviours and the potential for interventions targeting such factors