Global and regional left ventricular myocardial deformation measures by magnetic resonance feature tracking in healthy volunteers: comparison with tagging and relevance of gender

This work was funded by a grant from the Engineering and Physical Sciences Research Council (EP/G030693/1) and supported by the Oxford British Heart Foundation Centre of Research Excellence and the National Institute for Health Research Oxford Biomedical Research Centr

Mass mortality of eastern box turtles with upper respiratory disease following atypical cold weather

Emerging infectious diseases cause population declines in many ectotherms, with outbreaks frequently punctuated by periods of mass mortality. It remains unclear, however, whether thermoregulation by ectotherms and variation in environmental temperature is associated with mortality risk and disease progression, especially in wild populations. Here, we examined environmental and body temperatures of free-ranging eastern box turtles Terrapene carolina during a mass die-off coincident with upper respiratory disease. We recorded deaths of 17 turtles that showed clinical signs of upper respiratory disease among 76 adult turtles encountered in Berea, Kentucky (USA), in 2014. Of the 17 mortalities, 11 occurred approximately 14 d after mean environmental temperature dropped 2.5 SD below the 3 mo mean. Partial genomic sequencing of the major capsid protein from 1 sick turtle identified a ranavirus isolate similar to frog virus 3. Turtles that lacked clinical signs of disease had significantly higher body temperatures (23°C) than sick turtles (21°C) during the mass mortality, but sick turtles that survived and recovered eventually warmed (measured by temperature loggers). Finally, there was a significant negative effect of daily environmental temperature deviation from the 3 mo mean on survival, suggesting that rapid decreases in environmental temperature were correlated with mortality. Our results point to a potential role for environmental temperature variation and body temperature in disease progression and mortality risk of eastern box turtles affected by upper respiratory disease. Given our findings, it is possible that colder or more variable environmental temperatures and an inability to effectively thermoregulate are associated with poorer disease outcomes in eastern box turtles

A Dynamic Model of Interactions of Ca^(2+), Calmodulin, and Catalytic Subunits of Ca^(2+)/Calmodulin-Dependent Protein Kinase II

During the acquisition of memories, influx of Ca^(2+) into the postsynaptic spine through the pores of activated N-methyl-D-aspartate-type glutamate receptors triggers processes that change the strength of excitatory synapses. The pattern of Ca^(2+) influx during the first few seconds of activity is interpreted within the Ca^(2+)-dependent signaling network such that synaptic strength is eventually either potentiated or depressed. Many of the critical signaling enzymes that control synaptic plasticity, including Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII), are regulated by calmodulin, a small protein that can bind up to 4 Ca^(2+) ions. As a first step toward clarifying how the Ca^(2+)-signaling network decides between potentiation or depression, we have created a kinetic model of the interactions of Ca^(2+), calmodulin, and CaMKII that represents our best understanding of the dynamics of these interactions under conditions that resemble those in a postsynaptic spine. We constrained parameters of the model from data in the literature, or from our own measurements, and then predicted time courses of activation and autophosphorylation of CaMKII under a variety of conditions. Simulations showed that species of calmodulin with fewer than four bound Ca^(2+) play a significant role in activation of CaMKII in the physiological regime, supporting the notion that processing ofCa^(2+) signals in a spine involves competition among target enzymes for binding to unsaturated species of CaM in an environment in which the concentration of Ca^(2+) is fluctuating rapidly. Indeed, we showed that dependence of activation on the frequency of Ca^(2+) transients arises from the kinetics of interaction of fluctuating Ca^(2+) with calmodulin/CaMKII complexes. We used parameter sensitivity analysis to identify which parameters will be most beneficial to measure more carefully to improve the accuracy of predictions. This model provides a quantitative base from which to build more complex dynamic models of postsynaptic signal transduction during learning

Impacts of savanna trees on forage quality for a large African herbivore

Recently, cover of large trees in African savannas has rapidly declined due to elephant pressure, frequent fires and charcoal production. The reduction in large trees could have consequences for large herbivores through a change in forage quality. In Tarangire National Park, in Northern Tanzania, we studied the impact of large savanna trees on forage quality for wildebeest by collecting samples of dominant grass species in open grassland and under and around large Acacia tortilis trees. Grasses growing under trees had a much higher forage quality than grasses from the open field indicated by a more favourable leaf/stem ratio and higher protein and lower fibre concentrations. Analysing the grass leaf data with a linear programming model indicated that large savanna trees could be essential for the survival of wildebeest, the dominant herbivore in Tarangire. Due to the high fibre content and low nutrient and protein concentrations of grasses from the open field, maximum fibre intake is reached before nutrient requirements are satisfied. All requirements can only be satisfied by combining forage from open grassland with either forage from under or around tree canopies. Forage quality was also higher around dead trees than in the open field. So forage quality does not reduce immediately after trees die which explains why negative effects of reduced tree numbers probably go initially unnoticed. In conclusion our results suggest that continued destruction of large trees could affect future numbers of large herbivores in African savannas and better protection of large trees is probably necessary to sustain high animal densities in these ecosystems

Large herbivores may alter vegetation structure of semi-arid savannas through soil nutrient mediation

In savannas, the tree–grass balance is governed by water, nutrients, fire and herbivory, and their interactions. We studied the hypothesis that herbivores indirectly affect vegetation structure by changing the availability of soil nutrients, which, in turn, alters the competition between trees and grasses. Nine abandoned livestock holding-pen areas (kraals), enriched by dung and urine, were contrasted with nearby control sites in a semi-arid savanna. About 40 years after abandonment, kraal sites still showed high soil concentrations of inorganic N, extractable P, K, Ca and Mg compared to controls. Kraals also had a high plant production potential and offered high quality forage. The intense grazing and high herbivore dung and urine deposition rates in kraals fit the accelerated nutrient cycling model described for fertile systems elsewhere. Data of a concurrent experiment also showed that bush-cleared patches resulted in an increase in impala dung deposition, probably because impala preferred open sites to avoid predation. Kraal sites had very low tree densities compared to control sites, thus the high impala dung deposition rates here may be in part driven by the open structure of kraal sites, which may explain the persistence of nutrients in kraals. Experiments indicated that tree seedlings were increasingly constrained when competing with grasses under fertile conditions, which might explain the low tree recruitment observed in kraals. In conclusion, large herbivores may indirectly keep existing nutrient hotspots such as abandoned kraals structurally open by maintaining a high local soil fertility, which, in turn, constrains woody recruitment in a negative feedback loop. The maintenance of nutrient hotspots such as abandoned kraals by herbivores contributes to the structural heterogeneity of nutrient-poor savanna vegetation

Long-Term Follow-Up of Patients after Acute Kidney Injury: Patterns of Renal Functional Recovery

Background and Objectives: Patients who survive acute kidney injury (AKI), especially those with partial renal recovery, present a higher long-term mortality risk. However, there is no consensus on the best time to assess renal function after an episode of acute kidney injury or agreement on the definition of renal recovery. In addition, only limited data regarding predictors of recovery are available. Design, Setting, Participants, & Measurements: From 1984 to 2009, 84 adult survivors of acute kidney injury were followed by the same nephrologist (RCRMA) for a median time of 4.1 years. Patients were seen at least once each year after discharge until end stage renal disease (ESRD) or death. In each consultation serum creatinine was measured and glomerular filtration rate estimated. Renal recovery was defined as a glomerular filtration rate value $60 mL/min/1.73 m2. A multiple logistic regression was performed to evaluate factors independently associated with renal recovery. Results: The median length of follow-up was 50 months (30–90 months). All patients had stabilized their glomerular filtration rates by 18 months and 83 % of them stabilized earlier: up to 12 months. Renal recovery occurred in 16 patients (19%) at discharge and in 54 (64%) by 18 months. Six patients died and four patients progressed to ESRD during the follow up period. Age (OR 1.09, p,0.0001) and serum creatinine at hospital discharge (OR 2.48, p = 0.007) were independent factors associated with non renal recovery. The acute kidney injury severity, evaluated by peak serum creatinine and nee

Association of temporal factors and suicides in the United States, 2000–2004

The purpose of the study was to examine the association of temporal factors, in particular days of the week and seasons of the year and death from suicide in the United States. Data were pooled from the Multiple Cause of Death Files. Hierarchical logistic regression models were fitted to all deaths occurring in 2000 through 2004 by suicide. The incidence of suicide was significantly higher on Wednesdays, compared to Sunday. Specifically, individuals were 99% more likely to kill themselves on Wednesday than on Sunday. Suicides were more prevalent in the summer months, and they were less likely to occur in winter. The state suicide rate significantly elevated individual suicide risk. The results held even after controlling for the potentially confounding effects of socio-economic and demographic variables at both the individual and state levels. It was concluded that the observed association between seasonality and suicide cannot be discounted as a mere coincidence. Future research ought to focus on integrating individual level data and contextual variables when testing for seasonality effects

Overview of Cell Signaling Pathways in Cancer

The final authenticated version is available online at https://doi.org/10.1007/978-3-319-95228-4_12

Smoke rings:towards a comprehensive tobacco free policy for the Olympic Games

Background The tobacco industry has long sought affiliation with major sporting events, including the Olympic Games, for marketing, advertising and promotion purposes. Since 1988, each Olympic Games has adopted a tobacco-free policy. Limited study of the effectiveness of the smoke-free policy has been undertaken to date, with none examining the tobacco industry's involvement with the Olympics or use of the Olympic brand. Methods and Findings A comparison of the contents of Olympic tobacco-free policies from 1988 to 2014 was carried out by searching the websites of the IOC and host NOCs. The specific tobacco control measures adopted for each Games were compiled and compared with measures recommended by the WHO Tobacco Free Sports Initiative and Article 13 of the Framework Convention on Tobacco Control (FCTC). This was supported by semi-structured interviews of key informants involved with the adoption of tobacco-free policies for selected games. To understand the industry's interests in the Olympics, the Legacy Tobacco Documents Library (http://legacy.library.ucsf.edu) was systematically searched between June 2013 and August 2014. Company websites, secondary sources and media reports were also searched to triangulate the above data sources. This paper finds that, while most direct associations between tobacco and the Olympics have been prohibited since 1988, a variety of indirect associations undermine the Olympic tobacco-free policy. This is due to variation in the scope of tobacco-free policies, limited jurisdiction and continued efforts by the industry to be associated with Olympic ideals. Conclusions The paper concludes that, compatible with the IOC's commitment to promoting healthy lifestyles, a comprehensive tobacco-free policy with standardized and binding measures should be adopted by the International Olympic Committee and all national Olympic committees

Protection from Experimental Cerebral Malaria with a Single Dose of Radiation-Attenuated, Blood-Stage Plasmodium berghei Parasites

BACKGROUND: Whole malaria parasites are highly effective in inducing immunity against malaria. Due to the limited success of subunit based vaccines in clinical studies, there has been a renewed interest in whole parasite-based malaria vaccines. Apart from attenuated sporozoites, there have also been efforts to use live asexual stage parasites as vaccine immunogens. METHODOLOGY AND RESULTS: We used radiation exposure to attenuate the highly virulent asexual blood stages of the murine malaria parasite P. berghei to a non-replicable, avirulent form. We tested the ability of the attenuated blood stage parasites to induce immunity to parasitemia and the symptoms of severe malaria disease. Depending on the mouse genetic background, a single high dose immunization without adjuvant protected mice from parasitemia and severe disease (CD1 mice) or from experimental cerebral malaria (ECM) (C57BL/6 mice). A low dose immunization did not protect against parasitemia or severe disease in either model after one or two immunizations. The protection from ECM was associated with a parasite specific antibody response and also with a lower level of splenic parasite-specific IFN-γ production, which is a mediator of ECM pathology in C57BL/6 mice. Surprisingly, there was no difference in the sequestration of CD8+ T cells and CD45+ CD11b+ macrophages in the brains of immunized, ECM-protected mice. CONCLUSIONS: This report further demonstrates the effectiveness of a whole parasite blood-stage vaccine in inducing immunity to malaria and explicitly demonstrates its effectiveness against ECM, the most pathogenic consequence of malaria infection. This experimental model will be important to explore the formulation of whole parasite blood-stage vaccines against malaria and to investigate the immune mechanisms that mediate protection against parasitemia and cerebral malaria