Bmc Med
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Poly(ADP-ribose) polymerases (PARP) are enzymes involved in DNA-damage repair. Inhibition of PARPs is a promising strategy for targeting cancers with defective DNA-damage repair, including BRCA1 and BRCA2 mutation-associated breast and ovarian cancers. Several PARP inhibitors are currently in trials in the adjuvant, neoadjuvant, and metastatic settings for the treatment of ovarian, BRCA-mutated breast, and other cancers. We herein review the development of PARP inhibitors and the basis for the excitement surrounding these agents, their use as single agents and in combinations, as well as their toxicities, mechanisms of acquired resistance, and companion diagnostics.
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The distribution of Plasmodium falciparum clinical malaria episodes is over-dispersed among children in endemic areas, with more children experiencing multiple clinical episodes than would be expected based on a Poisson distribution. There is consistent evidence for micro-epidemiological variation in exposure to P. falciparum. The aim of the current study was to identify children with excess malaria episodes after controlling for malaria exposure. ⋯ Of the models tested, the negative zero-inflated negative binomial distribution with exposure, calendar year, and age acting as independent predictors, fitted the distribution of clinical malaria the best. Despite accounting for these factors, a group of children suffer excess malaria episodes beyond those predicted by the model. An epidemiological framework for identifying these children will allow us to study factors that may explain excess malaria episodes.
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In this podcast, we talk to Professor Michael O'Donovan about the latest genetic advances in schizophrenia based on research data from the Schizophrenia Working Group of the Psychiatric Genomics Consortium. Functional and prediction studies from the identified genetic loci are described together with future directions in psychiatric genetics and its interplay with the environment. The podcast for this interview is available at http://media.biomedcentral.com/content/movies/supplementary/s12916-015-0417-1-s1.mp3.
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The academic community is under great pressure to publish. This pressure is compounded by high rejection rates at many journals. A more recent trend is for some journals to send invitations directly to researchers inviting them to submit a manuscript to their journals. ⋯ The majority of invitations included an unsubscribe link (n = 187; 60.1%). About half of the invitations came from biomedical journals (n = 179). We discuss strategies researchers and institutions can consider to reduce the number of invitations received and strategies to handle those invitations that make it to the recipients' inbox, thus helping to maintain the credibility and reputation of researchers and institutions.
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Chronic diseases contribute a large share of disease burden in low- and middle-income countries (LMICs). Chronic diseases have a tendency to occur simultaneously and where there are two or more such conditions, this is termed as 'multimorbidity'. Multimorbidity is associated with adverse health outcomes, but limited research has been undertaken in LMICs. Therefore, this study examines the prevalence and correlates of multimorbidity as well as the associations between multimorbidity and self-rated health, activities of daily living (ADLs), quality of life, and depression across six LMICs. ⋯ Findings highlight the challenge of multimorbidity in LMICs, particularly among the lower socioeconomic groups, and the pressing need for reorientation of health care resources considering the distribution of multimorbidity and its adverse effect on health outcomes.