97 research outputs found
Understanding Tradeoffs Between Food and Predation Risks in a Specialist Mammalian Herbivore
Understanding habitat use by animals requires understanding the simultaneous tradeoffs between food and predation risk within a landscape. Quantifying the synergy between patches that provide quality food and those that are safe from predators at a scale relevant to a foraging animal could better reveal the parameters that influence habitat selection. To understand more thoroughly how animals select habitat components, we investigated tradeoffs between diet quality and predation risk in a species endemic to sagebrush Artemisia spp. communities in North America, the pygmy rabbitBrachylagus idahoensis. This species is a rare example of a specialist herbivore that relies almost entirely on sagebrush for food and cover. We hypothesized that pygmy rabbits would forage in areas with low food risk (free of plant secondary metabolites, PSMs) and low predation risk (high concealment). However, because of relatively high tolerance to PSMs in sagebrush by pygmy rabbits, we hypothesized that they would trade off the risk of PSM-containing food to select lower predation risk when risks co-occurred. We compared food intake of pygmy rabbits during three double-choice trials designed to examine tradeoffs by offering animals two levels of food risk (1,8-cineole, a PSM) and predation risk (concealment cover). Rabbits ate more food at feeding stations with PSM-free food and high concealment cover. However, interactions between PSMs and cover suggested that the value of PSM-free food could be reduced if concealment is low and the value of high concealment can decrease if food contains PSMs. Furthermore, foraging decisions by individual rabbits suggested variation in tolerance of food or predation risks
Mechanical unloading activates FoxO3 to trigger Bnip3âdependent cardiomyocyte atrophy
BACKGROUND: Mechanical assist device therapy has emerged recently as an important and rapidly expanding therapy in advanced heart failure, triggering in some patients a beneficial reverse remodeling response. However, mechanisms underlying this benefit are unclear. METHODS AND RESULTS: In a model of mechanical unloading of the left ventricle, we observed progressive myocyte atrophy, autophagy, and robust activation of the transcription factor FoxO3, an established regulator of catabolic processes in other cell types. Evidence for FoxO3 activation was similarly detected in unloaded failing human myocardium. To determine the role of FoxO3 activation in cardiac muscle in vivo, we engineered transgenic mice harboring a cardiomyocyteâspecific constitutively active FoxO3 mutant (caFoxO3(flox);αMHCâMerâCreâMer). Expression of caFoxO3 triggered dramatic and progressive loss of cardiac mass, robust increases in cardiomyocyte autophagy, declines in mitochondrial biomass and function, and early mortality. Whereas increases in cardiomyocyte apoptosis were not apparent, we detected robust increases in Bnip3 (Bcl2/adenovirus E1B 19âkDa interacting protein 3), an established downstream target of FoxO3. To test the role of Bnip3, we crossed the caFoxO3(flox);αMHCâMerâCreâMer mice with Bnip3ânull animals. Remarkably, the atrophy and autophagy phenotypes were significantly blunted, yet the early mortality triggered by FoxO3 activation persisted. Rather, declines in cardiac performance were attenuated by proteasome inhibitors. Consistent with involvement of FoxO3âdriven activation of the ubiquitinâproteasome system, we detected timeâdependent activation of the atrogenes program and sarcomere protein breakdown. CONCLUSIONS: In aggregate, these data point to FoxO3, a protein activated by mechanical unloading, as a master regulator that governs both the autophagyâlysosomal and ubiquitinâproteasomal pathways to orchestrate cardiac muscle atrophy
Coronary CT Angiography and 5-Year Risk of Myocardial Infarction.
BACKGROUND: Although coronary computed tomographic angiography (CTA) improves diagnostic certainty in the assessment of patients with stable chest pain, its effect on 5-year clinical outcomes is unknown. METHODS: In an open-label, multicenter, parallel-group trial, we randomly assigned 4146 patients with stable chest pain who had been referred to a cardiology clinic for evaluation to standard care plus CTA (2073 patients) or to standard care alone (2073 patients). Investigations, treatments, and clinical outcomes were assessed over 3 to 7 years of follow-up. The primary end point was death from coronary heart disease or nonfatal myocardial infarction at 5 years. RESULTS: The median duration of follow-up was 4.8 years, which yielded 20,254 patient-years of follow-up. The 5-year rate of the primary end point was lower in the CTA group than in the standard-care group (2.3% [48 patients] vs. 3.9% [81 patients]; hazard ratio, 0.59; 95% confidence interval [CI], 0.41 to 0.84; P=0.004). Although the rates of invasive coronary angiography and coronary revascularization were higher in the CTA group than in the standard-care group in the first few months of follow-up, overall rates were similar at 5 years: invasive coronary angiography was performed in 491 patients in the CTA group and in 502 patients in the standard-care group (hazard ratio, 1.00; 95% CI, 0.88 to 1.13), and coronary revascularization was performed in 279 patients in the CTA group and in 267 in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91 to 1.27). However, more preventive therapies were initiated in patients in the CTA group (odds ratio, 1.40; 95% CI, 1.19 to 1.65), as were more antianginal therapies (odds ratio, 1.27; 95% CI, 1.05 to 1.54). There were no significant between-group differences in the rates of cardiovascular or noncardiovascular deaths or deaths from any cause. CONCLUSIONS: In this trial, the use of CTA in addition to standard care in patients with stable chest pain resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years than standard care alone, without resulting in a significantly higher rate of coronary angiography or coronary revascularization. (Funded by the Scottish Government Chief Scientist Office and others; SCOT-HEART ClinicalTrials.gov number, NCT01149590 .)
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Dans le cadre de cette troisiĂšme campagne, le travail sur le terrain (pl. 1) a Ă©tĂ© rĂ©parti entre : Des travaux archĂ©ologiques dans les zones Ă lâest, dites du « fort » et de la « jetĂ©e », dans le palais, dans la zone des fours, dans les tombes au nord et Ă lâest du « fort » ainsi quâĂ lâest de la zone des fours. Ils ont Ă©tĂ© complĂ©tĂ©s par une Ă©tude anthropologique sur les ossements provenant des sĂ©pultures. Travaux gĂ©oarchĂ©ologiques pour localiser lâancien chenal du Nil Ă lâest du site. Travau..
Global 30â240 keV proton precipitation in the 17â18 April 2002 geomagnetic storms: 2. Conductances and beam spreading
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95032/1/jgra18676.pd
The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe
The preponderance of matter over antimatter in the early Universe, the
dynamics of the supernova bursts that produced the heavy elements necessary for
life and whether protons eventually decay --- these mysteries at the forefront
of particle physics and astrophysics are key to understanding the early
evolution of our Universe, its current state and its eventual fate. The
Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed
plan for a world-class experiment dedicated to addressing these questions. LBNE
is conceived around three central components: (1) a new, high-intensity
neutrino source generated from a megawatt-class proton accelerator at Fermi
National Accelerator Laboratory, (2) a near neutrino detector just downstream
of the source, and (3) a massive liquid argon time-projection chamber deployed
as a far detector deep underground at the Sanford Underground Research
Facility. This facility, located at the site of the former Homestake Mine in
Lead, South Dakota, is approximately 1,300 km from the neutrino source at
Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino
charge-parity symmetry violation and mass ordering effects. This ambitious yet
cost-effective design incorporates scalability and flexibility and can
accommodate a variety of upgrades and contributions. With its exceptional
combination of experimental configuration, technical capabilities, and
potential for transformative discoveries, LBNE promises to be a vital facility
for the field of particle physics worldwide, providing physicists from around
the globe with opportunities to collaborate in a twenty to thirty year program
of exciting science. In this document we provide a comprehensive overview of
LBNE's scientific objectives, its place in the landscape of neutrino physics
worldwide, the technologies it will incorporate and the capabilities it will
possess.Comment: Major update of previous version. This is the reference document for
LBNE science program and current status. Chapters 1, 3, and 9 provide a
comprehensive overview of LBNE's scientific objectives, its place in the
landscape of neutrino physics worldwide, the technologies it will incorporate
and the capabilities it will possess. 288 pages, 116 figure
Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial
Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma.
Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We
aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding.
Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries.
Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the
minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and
had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were
randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical
apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to
100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a
maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h
for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to
allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients
who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable.
This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124.
Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid
(5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated
treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the
tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82â1·18).
Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and
placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein
thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of
5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98).
Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our
results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a
randomised trial
Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study
Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28â2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65â3·22], p\textless0·0001), American Society of Anesthesiologists grades 3â5 versus grades 1â2 (2·35 [1·57â3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01â2·39], p=0·046), emergency versus elective surgery (1·67 [1·06â2·63], p=0·026), and major versus minor surgery (1·52 [1·01â2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research
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