Predictive Modelling for Anuran Responses to Climate Change in Tropical Montane Ecosystems

Climate change poses a serious threat to many species globally. Potential responses are shifting range, adapting (e.g., phenological changes) or face extinction. Tropical montane ecosystems are particularly vulnerable to shifts in future climate due to rapid land use change, high population growth and multiple changes in the climate system, such as shifts and intensity of seasonality. Climate Change Vulnerability Assessment (CCVA) through Species Distribution Modelling (SDMs) provides a means of spatially assessing the potential impact of climate change on species ranges, but SDMs are limited in application by incomplete distribution data, a particularly acute challenge with rare and narrow ranging species. Malagasy amphibians exemplify the problems of SDMs in CCVA: two-thirds (166 species) have insufficient distribution data to run an SDM. This thesis developed a Trait Distribution Model (TDM) framework to spatially assess the climate-change vulnerability of data-poor, threatened Malagasy amphibians for the first time. By grouping species into trait complexes and then pooling distribution records, TDMs were used to assess the distributions of amphibian communities along environmental gradients. Threatened species clustered into three complexes; arboreal specialists, understorey species and habitat specialists. TDMs predicted the spatial distribution of all species in the landscape, but that ability improved as species’ range sizes and distribution data decreased. Correlations between trait complexes and water deficit suggested high levels of climate vulnerability for Malagasy amphibians by 2085, particularly arboreal species. However, omission of habitat variables led to spatial over-prediction, by up to 60%, for specialised species under current climate conditions. Subsequent ‘climate+habitat’ models revealed that up to eight threatened amphibian species face heightened extinction risk from climate change. Species losses are concentrated in lowland and mid-altitudinal zones, with no projected losses of tropical montane species. TDMs can indicate habitat management at the community level and be part of conservation planning under projected climate change

Predicted impact of climate change on the distribution of the Critically Endangered golden mantella (Mantella aurantiaca) in Madagascar

The impact of climate change on Malagasy amphibians remains poorly understood. Equally, deforestation, fragmentation, and lack of connectivity between forest patches may leave vulnerable species isolated in habitat that no longer suits their environmental or biological requirements. We assess the predicted impact of climate change by 2085 on the potential distribution of a Critically Endangered frog species, the golden mantella (Mantella aurantiaca), that is confined to a small area of the central rainforest of Madagascar. We identify potential population distributions and climatically stable areas. Results suggest a potential south-eastwardly shift away from the current range and a decrease in suitable habitat from 2110 km2 under current climate to between 112 km2 – 138 km2 by the year 2085 – less than 7% of currently available suitable habitat. Results also indicate that the amount of golden mantella habitat falling within protected areas decreases by 86% over the same period. We recommend research to ascertain future viability and the feasibility of expanding protection to newly identified potential sites. This information can then be used in future conservation actions such as habitat restoration, translocations, re-introductions or the siting of further wildlife corridors or protected areas

Microhabitat preference of the critically endangered golden mantella frog in Madagascar

The golden mantella (Mantella aurantiaca) is a critically endangered (CR) frog, endemic to the eastern rainforests of Madagascar. Although the species is very popular in the pet trade and widely bred in captivity, its specific habitat requirements in the wild are poorly understood. Ten forested sites in the Moramanga district of Madagascar were surveyed for microhabitat and environmental variables, and the presence or absence of golden mantellas in quadrats positioned along transects in the vicinity of breeding sites. Mixed models were used to determine which variables best explained microhabitat use by golden mantellas. Sites where golden mantellas were found tended to have surface temperatures of 2023 ˚C, UVI units at about 2.9, about 30 % canopy cover, and around 30 % herbaceous cover. Within sites, golden mantellas preferred microhabitats that had 70 % leaf litter coverage and relatively low numbers of tree roots. This information can be used to improve the identification and management of habitats in the wild, as well as to refine captive husbandry need

Improving hypertension management through pharmacist prescribing; the rural alberta clinical trial in optimizing hypertension (Rural RxACTION): trial design and methods

<p>Abstract</p> <p>Background</p> <p>Patients with hypertension continue to have less than optimal blood pressure control, with nearly one in five Canadian adults having hypertension. Pharmacist prescribing is gaining favor as a potential clinically efficacious and cost-effective means to improve both access and quality of care. With Alberta being the first province in Canada to have independent prescribing by pharmacists, it offers a unique opportunity to evaluate outcomes in patients who are prescribed antihypertensive therapy by pharmacists.</p> <p>Methods</p> <p>The study is a randomized controlled trial of enhanced pharmacist care, with the unit of randomization being the patient. Participants will be randomized to enhanced pharmacist care (patient identification, assessment, education, close follow-up, and prescribing/titration of antihypertensive medications) or usual care. Participants are patients in rural Alberta with undiagnosed/uncontrolled blood pressure, as defined by the Canadian Hypertension Education Program. The primary outcome is the change in systolic blood pressure between baseline and 24 weeks in the enhanced-care versus usual-care arms. There are also three substudies running in conjunction with the project examining different remuneration models, investigating patient knowledge, and assessing health-resource utilization amongst patients in each group.</p> <p>Discussion</p> <p>To date, one-third of the required sample size has been recruited. There are 15 communities and 17 pharmacists actively screening, recruiting, and following patients. This study will provide high-level evidence regarding pharmacist prescribing.</p> <p>Trial Registration</p> <p>Clinicaltrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00878566">NCT00878566</a>.</p

Changes in heart failure medications in patients hospitalised and discharged

BACKGROUND: To date, evidence-based recommendations help doctors to manage patients with heart failure (HF). However, the implementation of these recommendations in primary care is still problematic as beneficial drugs are infrequently prescribed. The aim of the study was to determine whether admission to hospital increases usage of beneficial HF medication and if this usage is maintained directly after discharge. METHODS: The study was conducted from November 2002 until January 2004. In 77 patients hospitalised with heart failure (HF), the medication prescribed by the referring general practitioner (GP) and drug treatment directed by the hospital physicians was documented. Information regarding the post-discharge (14 d) therapy by the GP was evaluated via a telephone interview. Ejection fraction values, comorbidity and specifics regarding diagnostic or therapeutic intervention were collected by chart review. RESULTS: When compared to the referring GPs, hospital physicians prescribed more ACE-inhibitors (58.4% vs. 76.6%; p = 0.001) and beta-blockers of proven efficacy in HF (metoprolol, bisoprolol, carvedilol; 58.4% vs. 81.8%). Aldosterone antagonists were also administered more frequently in the hospital setting compared to general practice (14.3% vs. 37.7%). The New York Heart Association classification for heart failure did not influence whether aldosterone antagonists were administered either in primary or secondary care. Fourteen days after discharge, there was no significant discontinuity in discharge medication. CONCLUSION: Patients suffering from HF were more likely to receive beneficial medication in hospital than prior to admission. The treatment regime then remained stable two weeks after discharge. We suggest that findings on drug continuation in different cardiovascular patients might be considered validated for patients with HF

Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study

Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Conclusions Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Trial registration Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Daily activity profile of the golden mantella in the 'Froggotron' - A replicated behavioral monitoring system for amphibians

Research on threatened species in zoos can provide vital information to inform conservation planning and implementation in the field. This is particularly important for rare and cryptic species with behavior patterns that are difficult to observe in the wild. The Critically Endangered golden mantella (Mantella aurantiaca) is an iconic, endemic frog confined to mid-altitude subhumid forest in Moramanga District, Madagascar. Ecological and behavioral data for this highly threatened species are sparse, and conservation work will need to be informed by both in situ and ex situ research on behavior and habitat preferences. This study utilized environmental information gathered in the field to design a system where behavior and microhabitat use could be measured in captivity. Using replicated climatically controlled chambers (the “Froggotrons”), we analysed the 24-hour activity profile of the golden mantella in relation to temperature and humidity. Golden mantellas showed a bimodal pattern of activity during the day with much less activity during the night. Frogs kept at warmer temperatures (20-25ºC) were more active than those kept under cooler conditions (16-19ºC). However, the bimodal pattern was retained under the different temperatures, although the second peak occurred slightly earlier under warmer conditions. Most activity was observed when humidity levels were above 85%, although less than half of the mantellas were active outside leaf microhabitats during peak periods. These findings can inform ongoing field surveys through determining the optimum times of day to either capture or count golden mantellas for further conservation actions

The pachytene checkpoint in Saccharomyces cerevisiae requires the Sum1 transcriptional repressor

Saccharomyces cerevisiae mutants that fail to complete meiotic recombination are blocked by the RAD17/RAD24/MEC1 checkpoint signaling pathway in pachytene when early sporulation genes are expressed. Middle genes are not activated in checkpoint-arrested cells because the Ndt80 transcription factor is inhibited. We find that the pachytene checkpoint requires Sum1, a transcriptional repressor that recognizes a subset of Ndt80-binding sites. Mutants lacking Sum1 or Rad17 partially bypass the block to the nuclear divisions but do not form spores, while mutants lacking both Sum1 and Rad17 completely bypass the block and form morphologically normal spores. The level of Sum1 protein decreases as middle genes are expressed, and this decrease is blocked in checkpoint-arrested cells. These data suggest that Sum1 levels are regulated by the checkpoint and that progression of the meiotic divisions and spore differentiation can be differentially controlled by competition of the Sum1 repressor and Ndt80 activator for occupancy at key middle promoters

CAK1 Promotes Meiosis and Spore Formation in Saccharomyces cerevisiae in a CDC28-Independent Fashion

CAK1 encodes a protein kinase in Saccharomyces cerevisiae whose sole essential mitotic role is to activate the Cdc28p cyclin-dependent kinase by phosphorylation of threonine-169 in its activation loop. SMK1 encodes a sporulation-specific mitogen-activated protein (MAP) kinase homolog that is required to regulate the postmeiotic events of spore wall assembly. CAK1 was previously identified as a multicopy suppressor of a weakened smk1 mutant and shown to be required for spore wall assembly. Here we show that Smk1p, like other MAP kinases, is phosphorylated in its activation loop and that Smk1p is not activated in a cak1 missense mutant. Strains harboring a hyperactivated allele of CDC28 that is CAK1 independent and that lacks threonine-169 still require CAK1 to activate Smk1p. The data indicate that Cak1p functions upstream of Smk1p by activating a protein kinase other than Cdc28p. We also found that mutants lacking CAK1 are blocked early in meiotic development, as they show substantial delays in premeiotic DNA synthesis and defects in the expression of sporulation-specific genes, including IME1. The early meiotic role of Cak1p, like the postmeiotic role in the Smk1p pathway, is CDC28 independent. The data indicate that Cak1p activates multiple steps in meiotic development through multiple protein kinase targets