536 research outputs found

    A spatial approach to combatting wildlife crime

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    Poaching can have devastating impacts on animal and plant numbers, and in many countries has reached crisis levels, with illegal hunters employing increasingly sophisticated techniques. We used data from an 8‐year study in Savé Valley Conservancy, Zimbabwe, to show how geographic profiling—a mathematical technique originally developed in criminology and recently applied to animal foraging and epidemiology—can be adapted for use in investigations of wildlife crime. The data set contained information on over 10,000 incidents of illegal hunting and the deaths of 6,454 wild animals. We used a subset of data for which the illegal hunters’ identities were known. Our model identified the illegal hunters’ home villages based on the spatial locations of the hunting incidences (e.g., snares). Identification of the villages was improved by manipulating the probability surface inside the conservancy to reflect the fact that although the illegal hunters mostly live outside the conservancy, the majority of hunting occurs inside the conservancy (in criminology terms, commuter crime). These results combined with rigorous simulations showed for the first time how geographic profiling can be combined with GIS data and applied to situations with more complex spatial patterns, for example, where landscape heterogeneity means some parts of the study area are less likely to be used (e.g., aquatic areas for terrestrial animals) or where landscape permeability differs (e.g., forest bats tend not to fly over open areas). More broadly, these results show how geographic profiling can be used to target antipoaching interventions more effectively and more efficiently and to develop management strategies and conservation plans in a range of conservation scenarios.TRAFFIC Southern and East Africa, the European Union, Wilderness Trust, Chicago Board of Trade, and the African Wildlife Conservation Fund.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1523-17392019-06-01hj2018Mammal Research InstituteZoology and Entomolog

    A conceptual cellular interaction model of left ventricular remodelling post-MI: dynamic network with exit-entry competition strategy

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    Abstract Background Progressive remodelling of the left ventricle (LV) following myocardial infarction (MI) is an outcome of spatial-temporal cellular interactions among different cell types that leads to heart failure for a significant number of patients. Cellular populations demonstrate temporal profiles of flux post-MI. However, little is known about the relationship between cell populations and the interaction strength among cells post-MI. The objective of this study was to establish a conceptual cellular interaction model based on a recently established graph network to describe the interaction between two types of cells. Results We performed stability analysis to investigate the effects of the interaction strengths, the initial status, and the number of links between cells on the cellular population in the dynamic network. Our analysis generated a set of conditions on interaction strength, structure of the network, and initial status of the network to predict the evolutionary profiles of the network. Computer simulations of our conceptual model verified our analysis. Conclusions Our study introduces a dynamic network to model cellular interactions between two different cell types which can be used to model the cellular population changes post-MI. The results on stability analysis can be used as a tool to predict the responses of particular cell populations

    Early recognition of coeliac disease through community pharmacies: A proof of concept study

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    Setting: 15 community pharmacies in the UK Objective: Proof of concept study to test the use of community pharmacies for active case finding of patients with coeliac disease. Method: Customers accessing over-the counter and prescription medicines indicated in the treatment of possible symptoms of coeliac disease over a six month period were offered a free point of care test. All patients were given advice regarding the test results and those who tested positive were advised to make an appointment with their general practitioner. Patients and pharmacists involved in service provision were asked to complete a satisfaction survey. Pharmacists were additionally invited to undertake interviews to better understand their views on the service. Main outcome measures: Feasibility of service, acceptability to stakeholders and proportion testing positive for coeliac disease. Results: Of the 551 individuals tested, 52 (9.4%) tested positive. 277 (50.3%) were tested for accessing irritable bowel syndrome treatment, 142 (25.8%) due to presenting for diarrhoea. The proportion of patients testing positive with different symptoms or for different treatments were similar. Of 43 customers who returned the satisfaction survey, all would recommend the service to others, believing the community pharmacy to be a suitable location. Community pharmacists believed that it enabled them to improve relationships with their customers and that medical practices were receptive to the service. Conclusion: This proof of concept study has shown that community pharmacies using a point of care test can effectively recognise and refer patients for confirmatory coeliac disease testing with high levels of customer and service provider satisfaction

    Should Research Ethics Encourage the Production of Cost-Effective Interventions?

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    This project considers whether and how research ethics can contribute to the provision of cost-effective medical interventions. Clinical research ethics represents an underexplored context for the promotion of cost-effectiveness. In particular, although scholars have recently argued that research on less-expensive, less-effective interventions can be ethical, there has been little or no discussion of whether ethical considerations justify curtailing research on more expensive, more effective interventions. Yet considering cost-effectiveness at the research stage can help ensure that scarce resources such as tissue samples or limited subject popula- tions are employed where they do the most good; can support parallel efforts by providers and insurers to promote cost-effectiveness; and can ensure that research has social value and benefits subjects. I discuss and rebut potential objections to the consideration of cost-effectiveness in research, including the difficulty of predicting effectiveness and cost at the research stage, concerns about limitations in cost-effectiveness analysis, and worries about overly limiting researchers’ freedom. I then consider the advantages and disadvantages of having certain participants in the research enterprise, including IRBs, advisory committees, sponsors, investigators, and subjects, consider cost-effectiveness. The project concludes by qualifiedly endorsing the consideration of cost-effectiveness at the research stage. While incorporating cost-effectiveness considerations into the ethical evaluation of human subjects research will not on its own ensure that the health care system realizes cost-effectiveness goals, doing so nonetheless represents an important part of a broader effort to control rising medical costs

    An essential function for the ATR-Activation-Domain (AAD) of TopBP1 in mouse development and cellular senescence

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    ATR activation is dependent on temporal and spatial interactions with partner proteins. In the budding yeast model, three proteins – Dpb11TopBP1, Ddc1Rad9 and Dna2 - all interact with and activate Mec1ATR. Each contains an ATR activation domain (ADD) that interacts directly with the Mec1ATR:Ddc2ATRIP complex. Any of the Dpb11TopBP1, Ddc1Rad9 or Dna2 ADDs is sufficient to activate Mec1ATR in vitro. All three can also independently activate Mec1ATR in vivo: the checkpoint is lost only when all three AADs are absent. In metazoans, only TopBP1 has been identified as a direct ATR activator. Depletion-replacement approaches suggest the TopBP1-AAD is both sufficient and necessary for ATR activation. The physiological function of the TopBP1 AAD is, however, unknown. We created a knock-in point mutation (W1147R) that ablates mouse TopBP1-AAD function. TopBP1-W1147R is early embryonic lethal. To analyse TopBP1-W1147R cellular function in vivo, we silenced the wild type TopBP1 allele in heterozygous MEFs. AAD inactivation impaired cell proliferation, promoted premature senescence and compromised Chk1 signalling following UV irradiation. We also show enforced TopBP1 dimerization promotes ATR-dependent Chk1 phosphorylation. Our data suggest that, unlike the yeast models, the TopBP1-AAD is the major activator of ATR, sustaining cell proliferation and embryonic development

    Donepezil, Anti-Alzheimer's Disease Drug, Prevents Cardiac Rupture during Acute Phase of Myocardial Infarction in Mice

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    Background: We have previously demonstrated that the chronic intervention in the cholinergic system by donepezil, an acetylcholinesterase inhibitor, plays a beneficial role in suppressing long-term cardiac remodeling after myocardial infarction (MI). In comparison with such a chronic effect, however, the acute effect of donepezil during an acute phase of MI remains unclear. Noticing recent findings of a cholinergic mechanism for anti-inflammatory actions, we tested the hypothesis that donepezil attenuates an acute inflammatory tissue injury following MI. Methods and Results: In isolated and activated macrophages, donepezil significantly reduced intra- and extracellular matrix metalloproteinase-9 (MMP-9). In mice with MI, despite the comparable values of heart rate and blood pressure, the donepezil-treated group showed a significantly lower incidence of cardiac rupture than the untreated group during the acute phase of MI. Immunohistochemistry revealed that MMP-9 was localized at the infarct area where a large number of inflammatory cells including macrophages infiltrated, and the expression and the enzymatic activity of MMP-9 at the left ventricular infarct area was significantly reduced in the donepezil-treated group. Conclusion: The present study suggests that donepezil inhibits the MMP-9-related acute inflammatory tissue injury in the infarcted myocardium, thereby reduces the risk of left ventricular free wall rupture during the acute phase of MI

    Human Platelet-Rich Plasma- and Extracellular Matrix-Derived Peptides Promote Impaired Cutaneous Wound Healing In Vivo

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    Previous work in our laboratory has described several pro-angiogenic short peptides derived from endothelial extracellular matrices degraded by bacterial collagenase. Here we tested whether these peptides could stimulate wound healing in vivo. Our experiments demonstrated that a peptide created as combination of fragments of tenascin X and fibrillin 1 (comb1) applied into cranial dermal wounds created in mice treated with cyclophosphamide to impair wound healing, can improve the rate of wound closure. Furthermore, we identify and characterize a novel peptide (UN3) created and modified from two naturally-occurring peptides, which are present in human platelet-rich plasma. In vitro testing of UN3 demonstrates that it causes a 50% increase in endothelial proliferation, 250% increase in angiogenic response and a tripling of epithelial cell migration in response to injury. Results of in vivo experiments where comb1 and UN3 peptides were added together to cranial wounds in cyclophosphamide-treated mice leads to improvement of wound vascularization as shown by an increase of the number of blood vessels present in the wound beds. Application of the peptides markedly promotes cellular responses to injury and essentially restores wound healing dynamics to those of normal, acute wounds in the absence of cyclophosphamide impairment. Our current work is aimed at understanding the mechanisms underlying the stimulatory effects of these peptides as well as identification of the cellular receptors mediating these effects.National Institutes of Health (U.S.) (Grant EY15125)National Institutes of Health (U.S.) (Grant EY19533)Wound Care Partners, LL

    Fibrin glue and transanal rectal advancement flap for high transsphincteric perianal fistulas; is there any advantage?

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    BACKGROUNDS AND AIM: In recent decades, fibrin glue has appeared as an alternative treatment for high perianal fistulas. Early results seemed promising, with high success rates being reported. However, with increasing follow-up, the enthusiasm was tempered because of disappointing results. The aim of this retrospective study was to assess the additional value of fibrin glue in combination with transanal advancement flap, compared to advancement flap alone, for the treatment of high transsphincteric fistulas of cryptoglandular origin. MATERIALS AND METHODS: Between January 1995 and January 2006, 127 patients were operated for high perianal fistulas with an advancement flap. After exclusion of patients with inflammatory bowel disease or HIV, 80 patients remained. A consecutive series of 26 patients had an advancement flap combined with obliteration of the fistula tract with fibrin glue. Patients were matched for prior fistula surgery, and the advancement was performed identically in all patients. In the fibrin glue group, glue was installed retrogradely in the fistula tract after the advancement was completed and the fistula tract had been curetted. RESULTS: Minimal follow-up after surgery was 13 months [median of 67 months (range, 13-127)]. The overall recurrence rate was 26% (n=21). Recurrence rates for advancement flap alone vs the combination with glue were 13% vs 56% (p=0.014) in the group without previous fistula surgery and 23% vs 41% (p=0.216) in the group with previous fistula surgery. CONCLUSION: Obliterating the fistula tract with fibrin glue was associated with worse outcome after rectal advancement flap for high perianal fistula
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