Pharmacodynamic Effects of a 6-Hour Regimen of Enoxaparin in Patients Undergoing Primary Percutaneous Coronary Intervention (PENNY PCI Study)

Delayed onset of action of oral P2Y₁₂ inhibitors in ST-elevation myocardial infarction (STEMI) patients may increase the risk of acute stent thrombosis. Available parenteral anti-thrombotic strategies, to deal with this issue, are limited by added cost and increased risk of bleeding. We investigated the pharmacodynamic effects of a novel regimen of enoxaparin in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Twenty patients were recruited to receive 0.75 mg/kg bolus of enoxaparin (pre-PPCI) followed by infusion of enoxaparin 0.75 mg/kg/6 h. At four time points (pre-anti-coagulation, end of PPCI, 2–3 hours into infusion and at the end of infusion), anti-Xa levels were determined using chromogenic assays, fibrin clots were assessed by turbidimetric analysis and platelet P2Y₁₂ inhibition was determined by VerifyNow P2Y₁₂ assay. Clinical outcomes were determined 14 hours after enoxaparin initiation. Nineteen of 20 patients completed the enoxaparin regimen; one patient, who developed no-reflow phenomenon, was switched to tirofiban after the enoxaparin bolus. All received ticagrelor 180 mg before angiography. Mean (± standard error of the mean) anti-Xa levels were sustained during enoxaparin infusion (1.17 ± 0.06 IU/mL at the end of PPCI and 1.003 ± 0.06 IU/mL at 6 hours), resulting in prolonged fibrin clot lag time and increased lysis potential. Onset of platelet P2Y₁₂ inhibition was delayed in opiate-treated patients. No patients had thrombotic or bleeding complications. In conclusion, enoxaparin 0.75 mg/kg bolus followed by 0.75 mg/kg/6 h provides sustained anti-Xa levels in PPCI patients. This may protect from acute stent thrombosis in opiate-treated PPCI patients who frequently have delayed onset of oral P2Y₁₂ inhibition

A Global Perspective on Trends in Nature-Based Tourism

Falling attendance at United States and Japanese national parks has led to claims of a pervasive shift away from nature-based recreation. A global analysis, however, now suggests that while visit rates are declining slightly in some richer countries, elsewhere nature tourism is booming

Habitat quality influences population distribution, individual space use and functional responses in habitat selection by a large herbivore

Identifying factors shaping variation in resource selection is central for our understanding of the behaviour and distribution of animals. We examined summer habitat selection and space use by 108 Global Positioning System (GPS)-collared moose in Norway in relation to sex, reproductive status, habitat quality, and availability. Moose selected habitat types based on a combination of forage quality and availability of suitable habitat types. Selection of protective cover was strongest for reproducing females, likely reflecting the need to protect young. Males showed strong selection for habitat types with high quality forage, possibly due to higher energy requirements. Selection for preferred habitat types providing food and cover was a positive function of their availability within home ranges (i.e. not proportional use) indicating functional response in habitat selection. This relationship was not found for unproductive habitat types. Moreover, home ranges with high cover of unproductive habitat types were larger, and smaller home ranges contained higher proportions of the most preferred habitat type. The distribution of moose within the study area was partly related to the distribution of different habitat types. Our study shows how distribution and availability of habitat types providing cover and high-quality food shape ungulate habitat selection and space use

West Antarctic ice loss influenced by internal climate variability and anthropogenic forcing

Recent ice loss from the West Antarctic Ice Sheet has been caused by ocean melting of ice shelves in the Amundsen Sea. Eastward wind anomalies at the shelf break enhance the import of warm Circumpolar Deep Water onto the Amundsen Sea continental shelf, which creates transient melting anomalies with an approximately decadal period. No anthropogenic influence on this process has been established. Here, we combine observations and climate model simulations to suggest that increased greenhouse gas forcing caused shelf-break winds to transition from mean easterlies in the 1920s to the near-zero mean zonal winds of the present day. Strong internal climate variability, primarily linked to the tropical Pacific, is superimposed on this forced trend. We infer that the Amundsen Sea experienced decadal ocean ariability throughout the twentieth century, with warm anomalies gradually becoming more prevalent, offering a credible explanation for the ongoing ice loss. Existing climate model projections show that strong future greenhouse gas forcing creates persistent mean westerly shelf-break winds by 2100, suggesting a further enhancement of warm ocean anomalies. These wind changes are weaker under a scenario in which greenhouse gas concentrations are stabilized

Design of an international multicentre RCT on group schema therapy for borderline personality disorder

Background Borderline personality disorder (BPD) is a severe and highly prevalent mental disorder. Schema therapy (ST) has been found effective in the treatment of BPD and is commonly delivered through an individual format. A group format (group schema therapy, GST) has also been developed. GST has been found to speed up and amplify the treatment effects found for individual ST. Delivery in a group format may lead to improved cost-effectiveness. An important question is how GST compares to treatment as usual (TAU) and what format for delivery of schema therapy (format A; intensive group therapy only, or format B; a combination of group and individual therapy) produces the best outcomes. Methods/Design An international, multicentre randomized controlled trial (RCT) will be conducted with a minimum of fourteen participating centres. Each centre will recruit multiple cohorts of at least sixteen patients. GST formats as well as the orders in which they are delivered to successive cohorts will be balanced. Within countries that contribute an uneven number of sites, the orders of GST formats will be balanced within a difference of one. The RCT is designed to include a minimum of 448 patients with BPD. The primary clinical outcome measure will be BPD severity. Secondary clinical outcome measures will include measures of BPD and general psychiatric symptoms, schemas and schema modes, social functioning and quality of life. Furthermore, an economic evaluation that consists of cost-effectiveness and cost-utility analyses will be performed using a societal perspective. Lastly, additional investigations will be carried out that include an assessment of the integrity of GST, a qualitative study on patients’ and therapists’ experiences with GST, and studies on variables that might influence the effectiveness of GST. Discussion This trial will compare GST to TAU for patients with BPD as well as two different formats for the delivery of GST. By combining an evaluation of clinical effectiveness, an economic evaluation and additional investigations, it will contribute to an evidence-based understanding of which treatment should be offered to patients with BPD from clinical, economic, and stakeholders’ perspectives

Trophic and functional cascades in tropical versus temperate aquatic microcosms

17 pages, 7 figures, 3 tablesInverse trophic cascades are a well explored and common consequence of the local depletion or extinction of top predators in natural ecosystems. Despite a large body of research, the cascading effects of predator removal on ecosystem functions are not as well understood. Developing microcosm experiments, we explored food web changes in trophic structure and ecosystem functioning following biomass removal of top predators in representative temperate and tropical rock pool communities that contained similar assemblages of zooplankton and benthic invertebrates. We observed changes in species abundances following predator removal in both temperate and tropical communities, in line with expected inverse effects of a trophic cascade, where predation release benefits the predator’s preys and competitors and impacts the preys of the latter. We also observed several changes at the community and ecosystem levels including a decrease in total abundance and mean trophic level of the community, and changes in chlorophyll-a and total dissolved particles. Our results also showed an increase in variability of both community and ecosystem processes following the removal of predators. These results illustrate how predator removal can lead to inverse trophic cascades both in structural and functioning properties, and can increase variability of ecosystem processes. Although observed patterns were consistent between tropical and temperate communities following an inverse cascade pattern, changes were more pronounced in the temperate community. Therefore, aquatic food webs may have inherent traits that condition ecosystem responses to changes in top-down trophic control and render some aquatic ecosystems especially sensitive to the removals of top predators.MC was supported financially by the European Commission Marie Curie Post-doctoral fellowship through the International Outgoing Fellowships (Call FP7-PEOPLE-2007-4-1-IOF) for the ECOFUN project. The authors thank Connie Tuck for sharing her experimental knowledge and data, and Dr. Heike Lotze and Dr. Tamara Romanuk for their support during the laboratory experiments and for their corrections and comments to the manuscript. They also thank Jess Wysmyck and Cathy Ryan for assistance with various analyses and to Aquatron staff from Dalhousie University for assistance with the microcosm cultures, and three reviewers for extensive and useful comments.Peer reviewe