The influence of spatiotemporal variation in ambient temperature on the ecology and physiology of birds

Ambient temperature has profound effects on the ecology, physiology and distribution of organisms. Ambient temperature regimes vary across spatial and temporal scales and understanding how organisms cope with this variation is a primary goal of ecological and evolutionary physiology. An emerging framework for understanding how geographic variation in ambient temperature is related to thermal physiology is the climatic variability hypothesis (CVH), which predicts that thermal tolerance breadth should increase with increasing levels of temperature variability. Studies documenting latitudinal increases in the thermal tolerance breadth of ectotherms and thermoneutral zone (TNZ –a proxy for thermal tolerance) breadth in endotherms have provided broad empirical support for the CVH. However, most previous tests of the CVH have focused on large-scale patterns of variation in thermal tolerance breadth across latitudinal temperature gradients, and little is known about how the CVH applies to small spatial scales (i.e. within a geographic locality) and also to temporal (seasonal) patterns of temperature variability. Furthermore, understanding how ambient temperature regime influences heat tolerances is becoming increasingly important due to climate warming, yet patterns of geographic variation in heat tolerances of endotherms have not been characterized. Finally, few studies have investigated the potential ecological consequences of variation in thermal physiology, particularly in endotherms. My dissertation chapters address each of these knowledge gaps in turn to provide a more complete investigation of the CVH and a clearer picture of how spatiotemporal variation in ambient temperature has influenced the physiology and ecology of birds. Chapter 2 explores the influence of ambient temperature regime on variation in TNZ breadth at multiple spatial scales. I captured ~140 bird species at three geographic localities (Illinois and South Carolina, U.S.A. and the Republic of Panama) and used flow-through respirometry to measure TNZ breadth. In phylogenetically informed analyses, I found that temperature variability rather than latitude per se was the best predictor of both interspecific and intraspecific geographic variation in TNZ breadth at large spatial scales (across geographic localities). I also found that migratory tendency was an important predictor of interspecific variation in TNZ breadth, with migratory species having TNZ breadths intermediate between temperate and tropical resident species. In contrast, at a smaller spatial scale (within a geographic locality), ecological traits associated with ambient temperature regime (vertical niche and habitat association) were not significant predictors of variation in TNZ breadth. My results indicate that temperature variability at the micro- or macro-habitat level is not associated with TNZ breadth in birds, and suggest that the CVH may not apply to smaller spatial scales in endotherms. Chapter 3 extends the CVH from spatial to temporal (seasonal) patterns of temperature variability and tests a secondary prediction of the CVH – that flexibility of thermoregulatory traits should increase with temperature seasonality. To test this prediction, I used flow-through respirometry to measure seasonal flexibility in five thermoregulatory traits [body mass (Mb), mass-adjusted basal metabolic rate (BMR), LCT, UCT and TNZ breadth] in suites of temperate (high seasonality) and tropical (low seasonality) birds. In phylogenetically-controlled analyses, I found that temperate species exhibited greater seasonal flexibility in LCT, UCT and TNZ breadth than did tropical species. Winter-acclimatized individuals of temperate species exhibited large reductions (up to ~9 °C) in LCT and modest (~2-3 °C) reductions in UCT relative to summer-acclimatized individuals, resulting in an increased winter TNZ breadth. Although some tropical species exhibited flexibility in LCT, UCT and TNZ breadth, patterns of seasonal flexibility were idiosyncratic and the mean amount of seasonal change was close to 0. In contrast, seasonal flexibility in Mb and mass-adjusted BMR did not differ between temperate and tropical species. My analysis suggests that patterns of geographic flexibility in thermoregulatory traits directly linked to thermal tolerance (e.g. LCT, UCT, TNZ breadth) conform to the CVH, whereas other traits (e.g. BMR, Mb) do not. Furthermore, the patterns I documented contribute to a growing body of evidence suggesting that species from environments with low temperature variability (e.g. lowland tropical species) may have reduced physiological flexibility relative to their temperate counterparts and may be more sensitive to climate change. Chapter 4 examines patterns of heat tolerance among tropical and temperate birds in an effort to provide the first analysis of geographic variation in avian heat tolerance. I then coupled heat tolerance data with ambient temperature data to test the prediction that tropical species will be more vulnerable than temperate species to future climate warming, as has been documented in numerous ectothermic taxa. I used flow-through respirometry coupled with temperature-sensitive passive integrated transponder (PIT) tags to measure three traits [UCT, heat-strain coefficient (HScoeff – the slope of the relationship between Tb and Ta above the UCT) and critical thermal maximum (CTmax – the Ta at which birds become hyperthermic and lose the ability to regulate Tb)] that comprise heat tolerance. Contrary to previous studies of ectotherms, I found limited evidence of reduced heat tolerances in tropical species. In phylogenetically-controlled analyses, although temperate species had slightly higher (~2 °C) CTmax, HScoeff and UCT did not differ between temperate and tropical birds. Importantly, these subtle differences in heat tolerance do not seem to translate into systematic differences in vulnerability to climate warming. Thermal safety margins did not differ significantly between temperate and tropical species, and seem to be large enough to allow for physiological tolerance of projected warming rates. Overall, my data do not indicate that tropical birds will be any more physiologically vulnerable to climate warming than temperate species, in contrast with previous patterns described in ectotherms. Chapter 5 focuses on the potential ecological consequences of variation in thermal physiology. Understory insectivorous birds of Neotropical forests are a guild that is disproportionately sensitive to disturbance, experiencing population declines and local extirpation in response to forest fragmentation. One hypothesis for their declines is the microclimate hypothesis, which posits that the novel abiotic conditions (i.e. increased temperature and solar radiation, decreased humidity) that habitat fragmentation introduces may physiologically challenge understory insectivores and contribute to their population declines. An important assumption of the microclimate hypothesis is that understory insectivores have narrow physiological tolerances because they inhabit the forest understory, which is an incredibly stable and buffered environment. To test the microclimate hypothesis, I radio-tagged individuals of nine understory insectivore species at three sites along a precipitation gradient in central Panama and compared the microclimates (ambient temperature, relative humidity, solar radiation) that they selected with randomly chosen microclimates to test for the preferential use of particular microclimates (i.e. microclimate selectivity). I found no evidence of selectivity for any of the nine species I sampled on a seasonal or spatial basis. Microclimate variation was minimal in the forest understory at all sites, particularly in the wet season. Understory insectivores did not use microhabitats characterized by high light intensity, and may be sensitive to light, though the mechanism remains unclear. The lack of microclimate variation in the understory of tropical forests may have serious fitness consequences for understory insectivores due to climate warming coupled with a lack of thermal refugia

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

International service trade and its implications for human resources for health: a case study of Thailand

This study aims at analysing the impact of international service trade on the health care system, particularly in terms of human resources for health (HRH), using Thailand as a case study. Information was gathered through a literature review and interviews of relevant experts, as well as a brainstorming session. It was found that international service trade has greatly affected the Thai health care system and its HRH. From 1965 to 1975 there was massive emigration of physicians from Thailand in response to increasing demand in the United States of America. The country lost about 1,500 physicians, 20% of its total number, during that period. External migration of health professionals occurred without relation to agreements on trade in services. It was also found that free trade in service sectors other than health could seriously affect the health care system and HRH. Free trade in financial services with free flow of low-interest foreign loans, which started in 1993 in Thailand, resulted in the mushrooming of urban private hospitals between 1994 and 1997. This was followed by intensive internal migration of health professionals from rural public to urban private hospitals. After the economic crisis in 1997, with the resulting downturn of the private health sector, reverse brain drain was evident. At the same time, foreign investors started to invest in the bankrupt private hospitals. Since 2001, the return of economic growth and the influx of foreign patients have started another round of internal brain drain

Malignant hyperthermia

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000–100,000 anesthesias. However, the prevalence of the genetic abnormalities may be as great as one in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The classic signs of MH include hyperthermia to marked degree, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. Early recognition of the signs of MH, specifically elevation of end-expired carbon dioxide, provides the clinical diagnostic clues. In humans the syndrome is inherited in autosomal dominant pattern, while in pigs in autosomal recessive. The pathophysiologic changes of MH are due to uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation. Due to ATP depletion, the muscle membrane integrity is compromised leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 90 mutations have been identified in the RYR-1 gene located on chromosome 19q13.1, and at least 25 are causal for MH. Diagnostic testing relies on assessing the in vitro contracture response of biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be used for identifying those at risk with greater frequency. Dantrolene sodium is a specific antagonist of the pathophysiologic changes of MH and should be available wherever general anesthesia is administered. Thanks to the dramatic progress in understanding the clinical manifestation and pathophysiology of the syndrome, the mortality from MH has dropped from over 80% thirty years ago to less than 5%

Ecologically Appropriate Xenobiotics Induce Cytochrome P450s in Apis mellifera

BACKGROUND: Honey bees are exposed to phytochemicals through the nectar, pollen and propolis consumed to sustain the colony. They may also encounter mycotoxins produced by Aspergillus fungi infesting pollen in beebread. Moreover, bees are exposed to agricultural pesticides, particularly in-hive acaricides used against the parasite Varroa destructor. They cope with these and other xenobiotics primarily through enzymatic detoxificative processes, but the regulation of detoxificative enzymes in honey bees remains largely unexplored. METHODOLOGY/PRINCIPAL FINDINGS: We used several approaches to ascertain effects of dietary toxins on bee susceptibility to synthetic and natural xenobiotics, including the acaricide tau-fluvalinate, the agricultural pesticide imidacloprid, and the naturally occurring mycotoxin aflatoxin. We administered potential inducers of cytochrome P450 enzymes, the principal biochemical system for Phase 1 detoxification in insects, to investigate how detoxification is regulated. The drug phenobarbital induces P450s in many insects, yet feeding bees with phenobarbital had no effect on the toxicity of tau-fluvalinate, a pesticide known to be detoxified by bee P450s. Similarly, no P450 induction, as measured by tau-fluvalinate tolerance, occurred in bees fed xanthotoxin, salicylic acid, or indole-3-carbinol, all of which induce P450s in other insects. Only quercetin, a common pollen and honey constituent, reduced tau-fluvalinate toxicity. In microarray comparisons no change in detoxificative gene expression was detected in phenobarbital-treated bees. However, northern blot analyses of guts of bees fed extracts of honey, pollen and propolis showed elevated expression of three CYP6AS P450 genes. Diet did not influence tau-fluvalinate or imidacloprid toxicity in bioassays; however, aflatoxin toxicity was higher in bees consuming sucrose or high-fructose corn syrup than in bees consuming honey. CONCLUSIONS/SIGNIFICANCE: These results suggest that regulation of honey bee P450s is tuned to chemicals occurring naturally in the hive environment and that, in terms of toxicological capacity, a diet of sugar is not equivalent to a diet of honey

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes