Attitudes of advanced Australian medical oncology trainees to rural practice

Aim: To identify the views of medical oncology trainees regarding rural training posts and rural practice overall, and to identify factors that may improve recruitment. Methods: A questionnaire was posted to all advanced oncology trainees in Australia in June 2006. The trainees were questioned on the perceived advantages and disadvantages of rural practice, their experience during previous rural rotations and potential incentives and barriers in recruiting trainees and specialist oncologists to regional and rural centers. Results: There was a 60% response rate. Of all participants 58% had considered rural practice. Those with a rural family background were more likely to have considered rural practice. Attitudes based on responses to listed disadvantages and advantages of rural practice were heterogenous. Lifestyle factors seemed to be of particular importance. Although there were perceived deficiencies in opportunities for professional education in rural oncology rotations, 94% felt their rotation had been a positive experience overall and 62% were more likely to consider a rural career following their rural rotation. Improving locum cover for leave was seen as a potential incentive by 97% trainees. Conclusion: Despite positive attitudes towards rural practice, many barriers exist preventing recruitment of medical oncology trainees to rural areas, in particular lifestyle factors that are difficult to modify. Factors that can be improved include improving access to clinical trials, enabling access to locum cover. Educational opportunities for current rural trainees need to be improved. Further study into potential incentives to enhance rural recruitment is required

Bile Acid Receptor Therapeutics Effects on Chronic Liver Diseases

In the past ten years, our understanding of the importance of bile acids has expanded from fat absorption and glucose/lipid/energy homeostasis into potential therapeutic targets for amelioration of chronic cholestatic liver diseases. The discovery of important bile acid signaling mechanisms, as well as their role in metabolism, has increased the interest in bile acid/bile acid receptor research development. Bile acid levels and speciation are dysregulated during liver injury/damage resulting in cytotoxicity, inflammation, and fibrosis. An increasing focus to target bile acid receptors, responsible for bile acid synthesis and circulation, such as Farnesoid X receptor and apical sodium-dependent bile acid transporter to reduce bile acid synthesis have resulted in clinical trials for treatment of previously untreatable chronic liver diseases such as non-alcoholic steatohepatitis and primary sclerosing cholangitis. This review focuses on current bile acid receptor mediators and their effects on parenchymal and non-parenchymal cells. Attention will also be brought to the gut/liver axis during chronic liver damage and its treatment with bile acid receptor modulators. Overall, these studies lend evidence to the importance of bile acids and their receptors on liver disease establishment and progression

Statistical considerations in a systematic review of proxy measures of clinical behaviour

Peer reviewedPublisher PD

Long-term impacts of mid-Holocene drier climatic conditions on Bolivian tropical dry forests

The Bolivian Chiquitano dry forest is the largest block of intact seasonally dry tropical forest in South America and is a priority ecoregion for conservation due to its high threat status. However, the long-term impacts of drier climatic conditions on tropical dry forests are not well understood, despite climate models predicting increased droughts over Bolivia in the coming century. In this paper, we assess the impacts of drier climatic conditions during the mid-Holocene on the Bolivian Chiquitano tropical dry forest using fossilised pollen, phytoliths, macro-charcoal, and geochemical proxies from a sediment core from a large lake (Laguna Mandioré) on the Bolivia–Brazil border. Our results show that drier climatic conditions during the mid- Holocene caused a local-scale, ecotonal expansion of upland savannah at the expense of dry forest. Interaction between drier climatic conditions and fire regime likely exerted a stronger control over the position of the dry forest–savannah ecotone than edaphic factors. However, the majority of the dry forest within the lake catchment maintained a closed canopy throughout the drier conditions of the mid-Holocene, despite floristic turnover towards more drought-tolerant taxa. These findings imply overall resilience of the Chiquitano dry forest biome to future drought, albeit with floristic changes and upland savannah encroachment at ecotones

The emerging role of cellular senescence in renal diseases

Cellular senescence represents the state of irreversible cell cycle arrest during cell division. Cellular senescence not only plays a role in diverse biological events such as embryogenesis, tissue regeneration and repair, ageing and tumour occurrence prevention, but it is also involved in many cardiovascular, renal and liver diseases through the senescence-associated secretory phenotype (SASP). This review summarizes the molecular mechanisms underlying cellular senescence and its possible effects on a variety of renal diseases. We will also discuss the therapeutic approaches based on the regulation of senescent and SASP blockade, which is considered as a promising strategy for the management of renal diseases

Country mapping: Kenya

The Population Council embarked on a three-year project to explore the acceptability of the progesterone vaginal ring (PVR) among women in sub-Saharan Africa and to develop a strategic plan for its introduction. This technical report presents the findings of the assessments in Kenya with specific focus on: (1) the country’s demographic profile; (2) the health systems, health policy, and family planning program context; and (3) stakeholder perspectives regarding the PVR. The findings suggest that the introduction of the PVR would fill a gap in the family planning needs of breastfeeding women in Kenya, and there is strong support from stakeholders for its future introduction. Given the health system challenges (staffing and infrastructure), there is a need for contraceptives that require little training on the part of the provider, do not require a sophisticated health infrastructure, are long-acting and thus do not require monthly visits to a health center, are user-friendly and woman-controlled, and are safe. The PVR addresses all of these concerns and, based on the information documented thus far, is likely to be a welcome addition to the existing contraceptive method mix in the country

Histamine stimulates the proliferation of small and large cholangiocytes by activation of both IP3/Ca2+ and cAMP-dependent signaling mechanisms

Although large cholangiocytes exert their functions by activation of cyclic adenosine 3',5'-monophosphate (cAMP), Ca(2+)-dependent signaling regulates the function of small cholangiocytes. Histamine interacts with four receptors, H1-H4HRs. H1HR acts by Gαq activating IP(3)/Ca(2+), whereas H2HR activates Gα(s) stimulating cAMP. We hypothesize that histamine increases biliary growth by activating H1HR on small and H2HR on large cholangiocytes. The expression of H1-H4HRs was evaluated in liver sections, isolated and cultured (normal rat intrahepatic cholangiocyte culture (NRIC)) cholangiocytes. In vivo, normal rats were treated with histamine or H1-H4HR agonists for 1 week. We evaluated: (1) intrahepatic bile duct mass (IBDM); (2) the effects of histamine, H1HR or H2HR agonists on NRIC proliferation, IP(3) and cAMP levels and PKCα and protein kinase A (PKA) phosphorylation; and (3) PKCα silencing on H1HR-stimulated NRIC proliferation. Small and large cholangiocytes express H1-H4HRs. Histamine and the H1HR agonist increased small IBDM, whereas histamine and the H2HR agonist increased large IBDM. H1HR agonists stimulated IP(3) levels, as well as PKCα phosphorylation and NRIC proliferation, whereas H2HR agonists increased cAMP levels, as well as PKA phosphorylation and NRIC proliferation. The H1HR agonist did not increase proliferation in PKCα siRNA-transfected NRICs. The activation of differential signaling mechanisms targeting small and large cholangiocytes is important for repopulation of the biliary epithelium during pathologies affecting different-sized bile ducts