Sense in Sensitivity: Assessing Species Vulnerability to Climate Change

This thesis investigates the impact of future climate change upon species vulnerability. Reports of shifts in species distributions are already numerous, but the pattern of change is not fully understood. This thesis looks to predict which species are likely to be most at risk under climate change and why? This thesis takes the equation; Vulnerability= Sensitivity + Exposure to better discover which species are most vulnerable to climate change. Additionally, this research explores how mitigation has a role in determining the degree to which species are vulnerable in the future. Determining a specie’s vulnerability to climate change required the creation of values representing each side of the equation, both a measure of sensitivity and exposure. The construction of a sensitivity measure required the creation of a life history and ecological traits database, and required the use of multiple methods of statistical analysis. Exposure was calculated using projections of future suitable climate space created using species distribution model Maxent. To explore the impact of mitigation on species vulnerability exposure was calculated under a range of climate change scenarios. The sensitivity and exposure scores are synthesised into a measure of vulnerability. The result of the equation, Vulnerability= Exposure + Sensitivity, has revealed which Mammal species are most vulnerable; those which will be exposed to a high degree of climate change and which life history and ecological traits make them sensitive. The most vulnerable species are those which are highly exposed and which have ‘slow’ life history traits, are range restricted, or, are climate specialist. The regions in which species are identified as most vulnerable include the Neotropical and Afrotropical zones. Mitigation is found to reduce potential vulnerability with early mitigation being the most beneficial. The deeper understanding gained through this research will help us prioritise species for conservation based on their vulnerability

Gender integration and intersectionality in food systems research for development: A guidance note

This Guidance Note highlights key points for gender integration in the research for development (R4D) project cycle. It uses an intersectional lens to recognize how aspects of social identity such as age or life stage, class, caste, ethnicity, ability, sexual orientation and so forth crosscut and shape gender and power. It provides an overall introduction, guide and set of signposts to help point you in the right direction

A half-century of geologic and geothermic investigations in Iceland: The legacy of Kristjn Smundsson

One of the World's premier field geologists, Kristján Sæmundsson led immense geological mapping programs and authored or co-authored nearly all geological maps of Iceland during the past half century, including the first modern bedrock and tectonic maps of the whole country. These monumental achievements collectively yield the most inclusive view of an extensional plate boundary anywhere on Earth. When Kristján began his work in 1961, the relation of Iceland to sea-floor spreading was not clear, and plate tectonics had not yet been invented. Kristján resolved key obstacles by demonstrating that the active rifting zones in Iceland had shifted over time and were linked by complex transforms to the mid-ocean spreading ridge, thus making the concept of sea-floor spreading in Iceland acceptable to those previously skeptical. Further, his insights and vast geological and tectonic knowledge on both high- and low-temperature geothermal areas in Iceland yielded a major increase in knowledge of geothermal systems, and probably no one has contributed more than he to Icelandic energy development. Kristján's legacy is comprised by his numerous superb maps on a variety of scales, the high quality papers he produced, the impactful ideas generated that were internationally diffused, and the generations of colleagues and younger people he inspired, mentored, or otherwise positively influenced with his knowledge and generous attitud

Hymen reconstruction as pragmatic empowerment? Results of a qualitative study from Tunisia

Hymen reconstruction surgery (HR), while ethically controversial, is now available in many countries. Little clinical evidence and hardly any surgical standards support the intervention. Nearly as scarce is social science research exploring women's motivations for the intervention, and health care professionals' justifications for its provision. In order to better understand decision-making processes, we conducted semi-structured interviews in metropolitan Tunis, in 2009, with six women seeking the procedure, four friends who supported such women, four physicians who perform the operation, and one midwife. Health care professionals and patient companions expressed moral ambivalence about HR: although they could comprehend the individual situation of the women, they expressed concern that availability of the procedure might further entrench the patriarchal norms that compel the motivation for seeking HR in the first place. Some women seeking HR shared this concern, but felt it was not outweighed by their personal aims, which were to marry and become mothers, or to overcome past violent sexual experiences. The women felt HR to be uniquely helpful in achieving these aims; all made pragmatic decisions about their bodies in a social environment dominated by patriarchal norms. The link between HR and pervasive gender injustice, including the credible threat of serious social and physical harm to women perceived to have failed to uphold the norm of virginity before marriage, raises questions about health care professionals' responsibility while facing requests for HR. Meaningful regulatory guidance must acknowledge that these genuine harms are at stake; it must do so, however, without resorting to moral double standards. We recommend a reframing of HR as a temporary resource for some women making pragmatic choices in a context of structural gender injustice. We reconfirm the importance of factual sexual and reproductive education, most importantly to counter distorted beliefs that conflate an “intact hymen” with virginity

Investigation of salicylate hepatic responses in comparison with chemical analogues of the drug

AbstractAnti-hyperglycaemic effects of the hydroxybenzoic acid salicylate might stem from effects of the drug on mitochondrial uncoupling, activation of AMP-activated protein kinase, and inhibition of NF-κB signalling. Here, we have gauged the contribution of these effects to control of hepatocyte glucose production, comparing salicylate with inactive hydroxybenzoic acid analogues of the drug. In rat H4IIE hepatoma cells, salicylate was the only drug tested that activated AMPK. Salicylate also reduced mTOR signalling, but this property was observed widely among the analogues. In a sub-panel of analogues, salicylate alone reduced promoter activity of the key gluconeogenic enzyme glucose 6-phosphatase and suppressed basal glucose production in mouse primary hepatocytes. Both salicylate and 2,6 dihydroxybenzoic acid suppressed TNFα-induced IκB degradation, and in genetic knockout experiments, we found that the effect of salicylate on IκB degradation was AMPK-independent. Previous data also identified AMPK-independent regulation of glucose but we found that direct inhibition of neither NF-κB nor mTOR signalling suppressed glucose production, suggesting that other factors besides these cell signalling pathways may need to be considered to account for this response to salicylate. We found, for example, that H4IIE cells were exquisitely sensitive to uncoupling with modest doses of salicylate, which occurred on a similar time course to another anti-hyperglycaemic uncoupling agent 2,4-dinitrophenol, while there was no discernible effect at all of two salicylate analogues which are not anti-hyperglycaemic. This finding supports much earlier literature suggesting that salicylates exert anti-hyperglycaemic effects at least in part through uncoupling

Metformin selectively targets redox control of complex I energy transduction

Many guanide-containing drugs are antihyperglycaemic but most exhibit toxicity, to the extent that only the biguanide metformin has enjoyed sustained clinical use. Here, we have isolated unique mitochondrial redox control properties of metformin that are likely to account for this difference. In primary hepatocytes and H4IIE hepatoma cells we found that antihyperglycaemic diguanides DG5-DG10 and the biguanide phenformin were up to 1000-fold more potent than metformin on cell signalling responses, gluconeogenic promoter expression and hepatocyte glucose production. Each drug inhibited cellular oxygen consumption similarly but there were marked differences in other respects. All diguanides and phenformin but not metformin inhibited NADH oxidation in submitochondrial particles, indicative of complex I inhibition, which also corresponded closely with dehydrogenase activity in living cells measured by WST-1. Consistent with these findings, in isolated mitochondria, DG8 but not metformin caused the NADH/NAD+ couple to become more reduced over time and mitochondrial deterioration ensued, suggesting direct inhibition of complex I and mitochondrial toxicity of DG8. In contrast, metformin exerted a selective oxidation of the mitochondrial NADH/NAD+ couple, without triggering mitochondrial deterioration. Together, our results suggest that metformin suppresses energy transduction by selectively inducing a state in complex I where redox and proton transfer domains are no longer efficiently coupled

Topography of Extracellular Matrix Mediates Vascular Morphogenesis and Migration Speeds in Angiogenesis

The extracellular matrix plays a critical role in orchestrating the events necessary for wound healing, muscle repair, morphogenesis, new blood vessel growth, and cancer invasion. In this study, we investigate the influence of extracellular matrix topography on the coordination of multi-cellular interactions in the context of angiogenesis. To do this, we validate our spatio-temporal mathematical model of angiogenesis against empirical data, and within this framework, we vary the density of the matrix fibers to simulate different tissue environments and to explore the possibility of manipulating the extracellular matrix to achieve pro- and anti-angiogenic effects. The model predicts specific ranges of matrix fiber densities that maximize sprout extension speed, induce branching, or interrupt normal angiogenesis, which are independently confirmed by experiment. We then explore matrix fiber alignment as a key factor contributing to peak sprout velocities and in mediating cell shape and orientation. We also quantify the effects of proteolytic matrix degradation by the tip cell on sprout velocity and demonstrate that degradation promotes sprout growth at high matrix densities, but has an inhibitory effect at lower densities. Our results are discussed in the context of ECM targeted pro- and anti-angiogenic therapies that can be tested empirically

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Rethinking the influence of hydroelectric development on gene flow in a long-lived fish, the Lake Sturgeon Acipenser fulvescens

Many hydroelectric dams have been in place for 50 - \u3e100 years, which for most fish species means that enough generations have passed for fragmentation induced divergence to have accumulated. However, for long-lived species such as Lake Sturgeon, Acipenser fulvescens, it should be possible to discriminate between historical population structuring and contemporary gene flow and improve the broader understanding of anthropogenic influence. On the Winnipeg River, Manitoba, two hypotheses were tested: 1) Measureable quantities of former reservoir dwelling Lake Sturgeon now reside downstream of the Slave Falls Generating Station, and 2) genetically differentiated populations of Lake Sturgeon occur upstream and downstream, a result of historical structuring. Genetic methods based on ten microsatellite markers were employed, and simulations were conducted to provide context. With regards to contemporary upstream to downstream contributions, the inclusion of length-at-age data proved informative. Both pairwise relatedness and Bayesian clustering analysis substantiated that fast-growing outliers, apparently entrained after residing in the upstream reservoir for several years, accounted for ~15% of the Lake Sturgeon 525–750 mm fork length captured downstream. With regards to historical structuring, upstream and downstream populations were found to be differentiated (FST = 0.011, and 0.013–0.014 when fast-growing outliers were excluded), and heterozygosity metrics were higher for downstream versus upstream juveniles. Historical asymmetric (downstream) gene flow in the vicinity of the generating station was the most logical explanation for the observed genetic structuring. In this section of the Winnipeg River, construction of a major dam does not appear to have fragmented a previously panmictic Lake Sturgeon population, but alterations to habitat may be influencing upstream to downstream contributions in unexpected ways