A coupled drug kinetics-cell cycle model to analyse the response of human cells to intervention by topotecan

A model describing the response of the growth of single human cells in the absence and presence of the anti-cancer agent topotecan (TPT) is presented. The model includes a novel coupling of both the kinetics of TPT and cell cycle responses to the agent. By linking the models in this way, rather than using separate (disjoint) approaches, it is possible to illustrate how the drug perturbs the cell cycle. The model is compared to experimental in vitro cell cycle response data (comprising single cell descriptors for molecular and behavioural events), showing good qualitative agreement for a range of TPT dose levels

A combined microfinance and training intervention can reduce HIV risk behaviour in young female participants.

OBJECTIVE: To assess effects of a combined microfinance and training intervention on HIV risk behavior among young female participants in rural South Africa. DESIGN: : Secondary analysis of quantitative and qualitative data from a cluster randomized trial, the Intervention with Microfinance for AIDS and Gender Equity study. METHODS: Eight villages were pair-matched and randomly allocated to receive the intervention. At baseline and after 2 years, HIV risk behavior was assessed among female participants aged 14-35 years. Their responses were compared with women of the same age and poverty group from control villages. Intervention effects were calculated using adjusted risk ratios employing village level summaries. Qualitative data collected during the study explored participants' responses to the intervention including HIV risk behavior. RESULTS: After 2 years of follow-up, when compared with controls, young participants had higher levels of HIV-related communication (adjusted risk ratio 1.46, 95% confidence interval 1.01-2.12), were more likely to have accessed voluntary counseling and testing (adjusted risk ratio 1.64, 95% confidence interval 1.06-2.56), and less likely to have had unprotected sex at last intercourse with a nonspousal partner (adjusted risk ratio 0.76, 95% confidence interval 0.60-0.96). Qualitative data suggest a greater acceptance of intrahousehold communication about HIV and sexuality. Although women noted challenges associated with acceptance of condoms by men, increased confidence and skills associated with participation in the intervention supported their introduction in sexual relationships. CONCLUSIONS: In addition to impacts on economic well being, women's empowerment and intimate partner violence, interventions addressing the economic and social vulnerability of women may contribute to reductions in HIV risk behavior

Early antenatal prediction of gestational diabetes in obese women: development of prediction tools for targeted intervention

All obese women are categorised as being of equally high risk of gestational diabetes (GDM) whereas the majority do not develop the disorder. Lifestyle and pharmacological interventions in unselected obese pregnant women have been unsuccessful in preventing GDM. Our aim was to develop a prediction tool for early identification of obese women at high risk of GDM to facilitate targeted interventions in those most likely to benefit. Clinical and anthropometric data and non-fasting blood samples were obtained at 15+0–18+6 weeks’ gestation in 1303 obese pregnant women from UPBEAT, a randomised controlled trial of a behavioural intervention. Twenty one candidate biomarkers associated with insulin resistance, and a targeted nuclear magnetic resonance (NMR) metabolome were measured. Prediction models were constructed using stepwise logistic regression. Twenty six percent of women (n = 337) developed GDM (International Association of Diabetes and Pregnancy Study Groups criteria). A model based on clinical and anthropometric variables (age, previous GDM, family history of type 2 diabetes, systolic blood pressure, sum of skinfold thicknesses, waist:height and neck:thigh ratios) provided an area under the curve of 0.71 (95%CI 0.68–0.74). This increased to 0.77 (95%CI 0.73–0.80) with addition of candidate biomarkers (random glucose, haemoglobin A1c (HbA1c), fructosamine, adiponectin, sex hormone binding globulin, triglycerides), but was not improved by addition of NMR metabolites (0.77; 95%CI 0.74–0.81). Clinically translatable models for GDM prediction including readily measurable variables e.g. mid-arm circumference, age, systolic blood pressure, HbA1c and adiponectin are described. Using a ≥35% risk threshold, all models identified a group of high risk obese women of whom approximately 50% (positive predictive value) later developed GDM, with a negative predictive value of 80%. Tools for early pregnancy identification of obese women at risk of GDM are described which could enable targeted interventions for GDM prevention in women who will benefit the most

Onset of experimental severe cardiac fibrosis is mediated by overexpression of angiotensin-converting enzyme 2

Angiotensin-converting enzyme (ACE) 2 is a recently identified homologue of ACE. There is great interest in the therapeutic benefit for ACE2 overexpression in the heart. However, the role of ACE2 in the regulation of cardiac structure and function, as well as maintenance of systemic blood pressure, remains poorly understood. In cell culture, ACE2 overexpression led to markedly increased myocyte volume, assessed in primary rabbit myocytes. To assess ACE2 function in vivo, we used a recombinant adeno-associated virus 6 delivery system to provide 11-week overexpression of ACE2 in the myocardium of stroke-prone spontaneously hypertensive rats. ACE2, as well as the ACE inhibitor enalapril, significantly reduced systolic blood pressure. However, in the heart, ACE2 overexpression resulted in cardiac fibrosis, as assessed by histological analysis with concomitant deficits in ejection fraction and fractional shortening measured by echocardiography. Furthermore, global gene expression profiling demonstrated the activation of profibrotic pathways in the heart mediated by ACE2 gene delivery. This study demonstrates that sustained overexpression of ACE2 in the heart in vivo leads to the onset of severe fibrosis

Energy Impacts of Water Based Recreation

The overall objective of the study reported here was to determine to what extent energy accounting could supplement and/or complement economic benfit/cost analyses of water management projects and to specifically examine the energy impacts of water based recreation. The energy accounting literature was carefully reviewed and an energy accounting methodology applicable to water management was devised. Data pertaining to receation at five reservoirs in Utah were assembled from visitation recoreds and on-site surveys. Energy requirements for site construction, travel to and from the recreation site, and recreation at the site were estimated. It was determined that energy devoted to water based recreation is not inconsequential. As much energy is devoted to recreation at Lake Powell alone as is required for all of production agriculture in Utah. It is suggested that while the models developed in this study could be used with confidence in the preparation of energy impact statements the authors are not persuaded energy accounting provides additional information to water use planners beyong that obtainable from traditional economic analysis

Coined quantum walks on percolation graphs

Quantum walks, both discrete (coined) and continuous time, form the basis of several quantum algorithms and have been used to model processes such as transport in spin chains and quantum chemistry. The enhanced spreading and mixing properties of quantum walks compared with their classical counterparts have been well-studied on regular structures and also shown to be sensitive to defects and imperfections in the lattice. As a simple example of a disordered system, we consider percolation lattices, in which edges or sites are randomly missing, interrupting the progress of the quantum walk. We use numerical simulation to study the properties of coined quantum walks on these percolation lattices in one and two dimensions. In one dimension (the line) we introduce a simple notion of quantum tunneling and determine how this affects the properties of the quantum walk as it spreads. On two-dimensional percolation lattices, we show how the spreading rate varies from linear in the number of steps down to zero, as the percolation probability decreases to the critical point. This provides an example of fractional scaling in quantum walk dynamics.Comment: 25 pages, 14 figures; v2 expanded and improved presentation after referee comments, added extra figur

A qualitative process evaluation of training for non-physician clinicians/associate clinicians (NPCs/ACs) in emergency maternal, neonatal care and clinical leadership, impact on clinical services improvements in rural Tanzania: the ETATMBA project: Table 1

Objectives The Enhancing Human Resources and Use of Appropriate Training for Maternal and Perinatal Survival in sub-Saharan Africa (ETATMBA) project is training non-physician clinicians as advanced clinical leaders in emergency maternal and newborn care in Tanzania and Malawi. The main aims of this process evaluation were to explore the implementation of the programme of training in Tanzania, how it was received, how or if the training has been implemented into practice and the challenges faced along the way. Design Qualitative interviews with trainees, trainers, district officers and others exploring the application of the training into practice. Participants During late 2010 and 2011, 36 trainees including 19 assistant medical officers one senior clinical officer and 16 nurse midwives/nurses (anaesthesia) were recruited from districts across rural Tanzania and invited to join the ETATMBA training programme. Results Trainees (n=36) completed the training returning to 17 facilities, two left and one died shortly after training. Of the remaining trainees, 27 were interviewed at their health facility. Training was well received and knowledge and skills were increased. There were a number of challenges faced by trainees, not least that their new skills could not be practised because the facilities they returned to were not upgraded. Nonetheless, there is evidence that the training is having an effect locally on health outcomes, like maternal and neonatal mortality, and the trainees are sharing their new knowledge and skills with others. Conclusions The outcome of this evaluation is encouraging but highlights that there are many ongoing challenges relating to infrastructure (including appropriate facilities, electricity and water) and the availability of basic supplies and drugs. This cadre of workers is a dedicated and valuable resource that can make a difference, which with better support could make a greater contribution to healthcare in the country

Can training non-physician clinicians/associate clinicians (NPCs/ACs) in emergency obstetric, neonatal care and clinical leadership make a difference to practice and help towards reductions in maternal and neonatal mortality in rural Tanzania? The ETATMBA project

Objectives During late 2010, 36 trainees including 19 assistant medical officers (AMOs) 1 senior clinical officer (CO) and 16 nurse midwives/nurses were recruited from districts across rural Tanzania and invited to join the Enhancing Human Resources and Use of Appropriate Technologies for Maternal and Perinatal Survival in the sub-Saharan Africa (ETATMBA) training programme. The ETATMBA project was training associate clinicians (ACs) as advanced clinical leaders in emergency obstetric care. The trainees returned to health facilities across the country with the hope of being able to apply their new skills and knowledge. The main aim of this study was to explore the impact of the ETATMBA training on health outcomes including maternal and neonatal morbidity and mortality in their facilities. Secondly, to explore the challenges faced in working in these health facilities. Design The study is a pre-examination/postexamination of maternal and neonatal health indicators and a survey of health facilities in rural Tanzania. The facilities surveyed were those in which ETATMBA trainees were placed post-training. The maternal and neonatal indicators were collected for 2011 and 2013 and the survey of the facilities was in early 2014. Results 16 of 17 facilities were surveyed. Maternal deaths show a non-significant downward trend over the 2 years (282–232 cases/100 000 live births). There were no significant differences in maternal, neonatal and birth complication variables across the time-points. The survey of facilities revealed shortages in key areas and some are a serious concern. Conclusions This study represents a snapshot of rural health facilities providing maternal and neonatal care in Tanzania. Enhancing knowledge, practical skills, and clinical leadership of ACs may have a positive impact on health outcomes. However, any impact may be confounded by the significant challenges in delivering a service in terms of resources. Thus, training may be beneficial, but it requires an infrastructure that supports it

Soil Fumigation for Plant Disease Control.

40 p

Isospin splitting in heavy baryons and mesons

A recent general analysis of light-baryon isospin splittings is updated and extended to charmed baryons. The measured $\Sigma_c$ and $\Xi_c$ splittings stand out as being difficult to understand in terms of two-body forces alone. We also discuss heavy-light mesons; though the framework here is necessarily less general, we nevertheless obtain some predictions that are not strongly model-dependent.Comment: 12 pages REVTEX 3, plus 4 uuencoded ps figures, CMU-HEP93-