The need for a convergence of agricultural/laboratory and zoo-based approaches to animal welfare

Advances in animal welfare science have led to a high number of studies published for farm, laboratory and zoo animals, with a huge breadth of innovative topic areas and methodologies. This paper investigates the different approaches used to undertake welfare research in farm, laboratory and zoo animals due to the variety of constraints that each group brings. We also set recommendations to how groups can support each other in moving forwards to reduce animal suffering and promote a life worth living, a goal that all parties aim to achieve. We propose that researchers develop more collaborations across species, in particular to focus on the applied component of animal welfare and utilizing positive welfare indicators; facilitate knowledge transfer and share good practice worldwide; and accept small n based studies that can still be scientifically robust and provide individual-based steps into advances in our knowledge. Ultimately, we need to be progressing animal welfare science to a point beyond legislative needs, and ensure that ‘high animal welfare’ becomes an additional mission statement for all animal-based industries

How Abnormal Is the Behaviour of Captive, Zoo-Living Chimpanzees?

Background. Many captive chimpanzees (Pan troglodytes) show a variety of serious behavioural abnormalities, some of which have been considered as possible signs of compromised mental health. The provision of environmental enrichments aimed at reducing the performance of abnormal behaviours is increasing the norm, with the housing of individuals in (semi-)natural social groups thought to be the most successful of these. Only a few quantitative studies of abnormal behaviour have been conducted, however, particularly for the captive population held in zoological collections. Consequently, a clear picture of the level of abnormal behaviour in zoo-living chimpanzees is lacking. Methods. We present preliminary findings from a detailed observational study of the behaviour of 40 socially-housed zoo-living chimpanzees from six collections in the United States of America and the United Kingdom. We determined the prevalence, diversity, frequency, and duration of abnormal behaviour from 1200 hours of continuous behavioural data collected by focal animal sampling. Results, conclusion, and significance. Our overall finding was that abnormal behaviour was present in all sampled individuals across six independent groups of zoo-living chimpanzees, despite the differences between these groups in size, composition, housing, etc. We found substantial variation between individuals in the frequency and duration of abnormal behaviour, but all individuals engaged in at least some abnormal behaviour and variation across individuals could not be explained by sex, age, rearing history or background (defined as prior housing conditions). Our data support a conclusion that, while most behaviour of zoo-living chimpanzees is ‘normal’ in that it is typical of their wild counterparts, abnormal behaviour is endemic in this population despite enrichment efforts. We suggest there is an urgent need to understand how the chimpanzee mind copes with captivity, an issue with both scientific and welfare implications

Immunophenotypic predictive profiling of BRCA1-associated breast cancer

The immunophenotypic predictive profile of BRCA1-associated cancers including major predictive markers, i.e., PARP-1, EGFR, c-kit, HER-2, and steroid hormones (ER/PR) that may have therapeutic relevance has not yet been reported in a comprehensive study. Using immunohistochemistry, we examined the expression of these proteins in a large cohort of BRCA1-associated breast cancers. PARP-1 immunoreactivity was found in 81.9%, EGFR in 43.6%, ER/PR in 17.9%, c-kit in 14.7%, and overexpression of HER-2 in 3.6% of cancers. For all markers studied, 8.2% of tumors were negative. Expression of only one predictive marker was found in 29.7% of cancers, and most frequently, it was PARP-1 (20.8%). In 62.1% of tumors, more than one predictive marker was expressed: PARP-1 and EGFR in 30.4%, PARP-1, and hormone receptors in 13.3% and PARP-1 with c-kit in 7.5% of all tumors. Coexpression of two or more other predictive markers was rare. There were significant differences in the median age at diagnosis of BRCA1-associated cancer between patients with ER+ vs. ER− and grades 1–2 vs. grade 3 tumors. These results demonstrate that BRCA1-associated cancers differ with respect to expression of proteins that are regarded as targets for specific therapies and that 92% of patients with BRCA1-associated cancers may benefit from one or several options for specific therapy (in addition to DNA damaging agents, e.g., cisplatin). About 8% of cancers which do not express therapeutic target proteins may not respond to such therapies. Knowledge of the immunophenotypic predictive profile may help with the recruitment of patients for trials of targeted therapies

FOXA1 repression is associated with loss of BRCA1 and increased promoter methylation and chromatin silencing in breast cancer

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_versio

Partner-based adherence intervention for second-line antiretroviral therapy (ACTG A5234): a multinational randomised trial

ACTG (AIDS Clinical Trials Group). The IPEC (INI - Fiocruz) site is one of the leading international sites in the ACTG network.Submitted by Fábio Marques ([email protected]) on 2018-10-15T14:55:36Z No. of bitstreams: 1 Partner-based Adherence Intervention for Second-line_Sandra_Cardoso_etal_INI_Lapclin-AIDS_2015.pdf: 528003 bytes, checksum: a3fe5499df665034615b85d576e29bc5 (MD5)Approved for entry into archive by Regina Costa ([email protected]) on 2018-10-17T15:24:34Z (GMT) No. of bitstreams: 1 Partner-based Adherence Intervention for Second-line_Sandra_Cardoso_etal_INI_Lapclin-AIDS_2015.pdf: 528003 bytes, checksum: a3fe5499df665034615b85d576e29bc5 (MD5)Made available in DSpace on 2018-10-17T15:24:34Z (GMT). No. of bitstreams: 1 Partner-based Adherence Intervention for Second-line_Sandra_Cardoso_etal_INI_Lapclin-AIDS_2015.pdf: 528003 bytes, checksum: a3fe5499df665034615b85d576e29bc5 (MD5) Previous issue date: 2015University of Pennsylvania Perelman School of Medicine, Medicine (Infectious Diseases) and Epidemiology. Philadelphia, PA, USA.Harvard School of Public Health. Biostatistics. Boston, MA, USA.Asociacion Civil IMPACTA Salud y Educacion. Lima, Peru.Harvard School of Public Health. Biostatistics. Boston, MA, USA.Harvard School of Public Health. Biostatistics. Boston, MA, USA.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Joint Clinical Research Centre. Kampala, Uganda.EUPATI. Barcelona, Spain.National Institute of Allergy and Infectious Diseases. Bethesda, MD, USA.Northwestern University Feinberg School of Medicine. Chicago, IL, USA.Massachusetts General Hospital and Harvard Medical School. Boston, MA, USA.University of Zimbabwe. Harare, Zimbabwe.Lancet Laboratories. Johannesburg, South Africa.Yale University School of Nursing. New Haven, CT USA.Harvard School of Public Health. Biostatistics. Boston, MA, USA.Massachusetts General Hospital and Harvard Medical School. Boston, MA, USA.Social and Scientific Systems. Silver Spring, MD, USA.GHESKIO. Port au Prince, Haiti.University of Washington. Seattle, WA, USA.Adherence is key to the success of antiretroviral therapy. Enhanced partner support might benefit patients with previous treatment failure. We aimed to assess whether an enhanced partner-based support intervention with modified directly observed therapy would improve outcomes with second-line therapy in HIV-infected patients for whom first-line therapy had failed