Towards best practice in management of road reserves

CITATION: Esler, K. J. & Milton, S. J. 2007. Towards best practice in management of road reserves. Veld & Flora, 93(1):11-12.The original publication is available at https://journals.co.za/journal/veldAn inevitable consequence of population pressure and a growing economy is that landscapes increasingly become converted to those where production and transport are primary concerns. The biodiversity-rich southern African landscapes are no exception to this global trend with our linear transport corridors (roads, power lines, railways) causing fragmentation of habitats. However, they can also be seen as essential linking corridors between habitat fragments where adjacent agricultural or urban activity has eliminated biodiversity.C.I.Bhttps://journals.co.za/doi/abs/10.10520/EJC113033Publisher’s versio

Osteopontin upregulation in rotavirus-induced murine biliary atresia requires replicating virus but is not necessary for development of biliary atresia

AbstractBiliary atresia (BA) is a progressive fibro-inflammatory pediatric liver disease in which osteopontin (OPN), a glycoprotein with inflammatory and fibrogenic activity, may play a pathogenic role. The current studies were conducted in a mouse model of rotavirus-induced BA to test the hypotheses that live but not inactivated rotavirus causes antigenemia, upregulation of hepatic OPN expression, and induction of BA and fibrosis; and that OPN is necessary for development of BA. Prolonged or transient antigenemia developed in mice inoculated with live or inactivated virus, respectively, but only live virus upregulated hepatic OPN and caused BA and fibrosis. OPN was expressed in intra- and extrahepatic bile ducts in healthy mice and in mice with BA. OPN-deficient mice, similar to WT mice, developed BA. Together, these data show that live but not inactivated rotavirus causes upregulation of hepatic OPN expression and BA but that OPN is not necessary for development of BA

Patient- and population-level health consequences of discontinuing antiretroviral therapy in settings with inadequate HIV treatment availability

Background In resource-limited settings, HIV budgets are flattening or decreasing. A policy of discontinuing antiretroviral therapy (ART) after HIV treatment failure was modeled to highlight trade-offs among competing policy goals of optimizing individual and population health outcomes. Methods In settings with two available ART regimens, we assessed two strategies: (1) continue ART after second-line failure (Status Quo) and (2) discontinue ART after second-line failure (Alternative). A computer model simulated outcomes for a single cohort of newly detected, HIV-infected individuals. Projections were fed into a population-level model allowing multiple cohorts to compete for ART with constraints on treatment capacity. In the Alternative strategy, discontinuation of second-line ART occurred upon detection of antiretroviral failure, specified by WHO guidelines. Those discontinuing failed ART experienced an increased risk of AIDS-related mortality compared to those continuing ART. Results At the population level, the Alternative strategy increased the mean number initiating ART annually by 1,100 individuals (+18.7%) to 6,980 compared to the Status Quo. More individuals initiating ART under the Alternative strategy increased total life-years by 15,000 (+2.8%) to 555,000, compared to the Status Quo. Although more individuals received treatment under the Alternative strategy, life expectancy for those treated decreased by 0.7 years (−8.0%) to 8.1 years compared to the Status Quo. In a cohort of treated patients only, 600 more individuals (+27.1%) died by 5 years under the Alternative strategy compared to the Status Quo. Results were sensitive to the timing of detection of ART failure, number of ART regimens, and treatment capacity. Although we believe the results robust in the short-term, this analysis reflects settings where HIV case detection occurs late in the disease course and treatment capacity and the incidence of newly detected patients are stable. Conclusions In settings with inadequate HIV treatment availability, trade-offs emerge between maximizing outcomes for individual patients already on treatment and ensuring access to treatment for all people who may benefit. While individuals may derive some benefit from ART even after virologic failure, the aggregate public health benefit is maximized by providing effective therapy to the greatest number of people. These trade-offs should be explicit and transparent in antiretroviral policy decisions

Complex Dynamics and Multistability in a Damped Harmonic Oscillator with Delayed Negative Feedback

A center manifold reduction and numerical calculations are used to demonstrate the presence of limit cycles, two-tori, and multistability in the damped harmonic oscillator with delayed negative feedback. This model is the prototype of a mechanical system operating with delayed feedback. Complex dynamics are thus seen to arise in very plausible and commonly occurring mechanical and neuromechanical feedback systems

Integrating qualitative research within a clinical trials unit: developing strategies and understanding their implementation in contexts

Background/aims: The value of using qualitative methods within clinical trials is widely recognised. How qualitative research is integrated within trials units to achieve this is less clear. This paper describes the process through which qualitative research has been integrated within Cardiff University’s Centre for Trials Research (CTR) in Wales, UK. We highlight facilitators of, and challenges to, integration. Methods: We held group discussions on the work of the Qualitative Research Group (QRG) within CTR. The content of these discussions, materials for a presentation in CTR, and documents relating to the development of the QRG were interpreted at a workshop attended by group members. Normalisation Process Theory (NPT) was used to structure analysis. A writing group prepared a document for input from members of CTR, forming the basis of this paper. Results: Actions to integrate qualitative research comprised: its inclusion in Centre strategies; formation of a QRG with dedicated funding/roles; embedding of qualitative research within operating systems; capacity building/training; monitoring opportunities to include qualitative methods in studies; maximising the quality of qualitative research and developing methodological innovation. Facilitators of these actions included: the influence of the broader methodological landscape within trial/study design and its promotion of the value of qualitative research; and close physical proximity of CTR qualitative staff/students allowing sharing of methodological approaches. Introduction of innovative qualitative methods generated interest among other staff groups. Challenges included: pressure to under-resource qualitative components of research, preference for a statistical stance historically in some research areas and funding structures, and difficulties faced by qualitative researchers carving out individual academic profiles when working across trials/studies. Conclusions: Given that CTUs are pivotal to the design and conduct of RCTs and related study types across multiple disciplines, integrating qualitative research into trials units is crucial if its contribution is to be fully realised. We have made explicit one trials unit’s experience of embedding qualitative research and present this to open dialogue on ways to operationalise and optimise qualitative research in trials. NPT provides a valuable framework with which to theorise these processes, including the importance of sense-making and legitimisation when introducing new practices within organisations

Assessing the Performance of a Computer-Based Policy Model of HIV and AIDS

BACKGROUND. Model-based analyses, conducted within a decision analytic framework, provide a systematic way to combine information about the natural history of disease and effectiveness of clinical management strategies with demographic and epidemiological characteristics of the population. Among the challenges with disease-specific modeling include the need to identify influential assumptions and to assess the face validity and internal consistency of the model. METHODS AND FINDINGS. We describe a series of exercises involved in adapting a computer-based simulation model of HIV disease to the Women's Interagency HIV Study (WIHS) cohort and assess model performance as we re-parameterized the model to address policy questions in the U.S. relevant to HIV-infected women using data from the WIHS. Empiric calibration targets included 24-month survival curves stratified by treatment status and CD4 cell count. The most influential assumptions in untreated women included chronic HIV-associated mortality following an opportunistic infection, and in treated women, the 'clinical effectiveness' of HAART and the ability of HAART to prevent HIV complications independent of virologic suppression. Good-fitting parameter sets required reductions in the clinical effectiveness of 1st and 2nd line HAART and improvements in 3rd and 4th line regimens. Projected rates of treatment regimen switching using the calibrated cohort-specific model closely approximated independent analyses published using data from the WIHS. CONCLUSIONS. The model demonstrated good internal consistency and face validity, and supported cohort heterogeneities that have been reported in the literature. Iterative assessment of model performance can provide information about the relative influence of uncertain assumptions and provide insight into heterogeneities within and between cohorts. Description of calibration exercises can enhance the transparency of disease-specific models.National Institute of Allergy and Infectious Diseases (R37 AI042006, K24 AI062476

The Baker's Yeast Diploid Genome Is Remarkably Stable in Vegetative Growth and Meiosis

Accurate estimates of mutation rates provide critical information to analyze genome evolution and organism fitness. We used whole-genome DNA sequencing, pulse-field gel electrophoresis, and comparative genome hybridization to determine mutation rates in diploid vegetative and meiotic mutation accumulation lines of Saccharomyces cerevisiae. The vegetative lines underwent only mitotic divisions while the meiotic lines underwent a meiotic cycle every ∼20 vegetative divisions. Similar base substitution rates were estimated for both lines. Given our experimental design, these measures indicated that the meiotic mutation rate is within the range of being equal to zero to being 55-fold higher than the vegetative rate. Mutations detected in vegetative lines were all heterozygous while those in meiotic lines were homozygous. A quantitative analysis of intra-tetrad mating events in the meiotic lines showed that inter-spore mating is primarily responsible for rapidly fixing mutations to homozygosity as well as for removing mutations. We did not observe 1–2 nt insertion/deletion (in-del) mutations in any of the sequenced lines and only one structural variant in a non-telomeric location was found. However, a large number of structural variations in subtelomeric sequences were seen in both vegetative and meiotic lines that did not affect viability. Our results indicate that the diploid yeast nuclear genome is remarkably stable during the vegetative and meiotic cell cycles and support the hypothesis that peripheral regions of chromosomes are more dynamic than gene-rich central sections where structural rearrangements could be deleterious. This work also provides an improved estimate for the mutational load carried by diploid organisms