Population connectivity in voles (Microtus sp.) as a gauge for tall grass prairie restoration in midwestern North America.

Ecological restoration can promote biodiversity conservation in anthropogenically fragmented habitats, but effectiveness of these management efforts need to be statistically validated to determine 'success.' One such approach is to gauge the extent of recolonization as a measure of landscape permeability and, in turn, population connectivity. In this context, we estimated dispersal and population connectivity in prairie vole (Microtus ochrogaster; N = 231) and meadow vole (M. pennsylvanicus; N = 83) within five tall-grass prairie restoration sites embedded within the agricultural matrix of midwestern North America. We predicted that vole dispersal would be constrained by the extent of agricultural land surrounding restored habitat patches, spatially isolating vole populations and resulting in significant genetic structure. We first employed genetic assignment tests based on 15 microsatellite DNA loci to validate field-derived species-designations, then tested reclassified samples with multivariate and Bayesian clustering to assay for spatial and temporal genetic structure. Population connectivity was further evaluated by calculating pairwise FST, then potential demographic effects explored by computing migration rates, effective population size (Ne), and average relatedness (r). Genetic species assignments reclassified 25% of initial field identifications (N = 11 M. ochrogaster; N = 67 M. pennsylvanicus). In M. ochrogaster population connectivity was high across the study area, reflected in little to no spatial or temporal genetic structure. In M. pennsylvanicus genetic structure was detected, but relatedness estimates identified it as kin-clustering instead, underscoring social behavior among populations rather than spatial isolation as the cause. Estimates of Ne and r were stable across years, reflecting high dispersal and demographic resilience. Combined, these metrics suggest the agricultural matrix is highly permeable for voles and does not impede dispersal. High connectivity observed confirms that the restored landscape is productive and permeable for specific management targets such as voles and also demonstrates population genetic assays as a tool to statistically evaluate effectiveness of conservation initiatives.

A minimal power model for human running performance.

Models for human running performances of various complexities and underlying principles have been proposed, often combining data from world record performances and bio-energetic facts of human physiology. The purpose of this work is to develop a novel, minimal and universal model for human running performance that employs a relative metabolic power scale. The main component is a self-consistency relation for the time dependent maximal power output. The analytic approach presented here is the first to derive the observed logarithmic scaling between world (and other) record running speeds and times from basic principles of metabolic power supply. Our hypothesis is that various female and male record performances (world, national) and also personal best performances of individual runners for distances from 800m to the marathon are excellently described by this model. Indeed, we confirm this hypothesis with mean errors of (often much) less than 1%. The model defines endurance in a way that demonstrates symmetry between long and short racing events that are separated by a characteristic time scale comparable to the time over which a runner can sustain maximal oxygen uptake. As an application of our model, we derive personalized characteristic race speeds for different durations and distances.

Survival of Lung Transplant Candidates With COPD: BODE Score Reconsidered.

BACKGROUND: The BMI, obstruction, dyspnea, and exercise capacity (BODE) score is used to inform prognostic considerations for lung transplantation for COPD, but it has not been validated in this context. A large proportion of mortality in COPD is attributable to comorbidities that could preclude transplant candidacy. We hypothesized that patients with COPD who are selected as transplant candidates experience better survival than traditional interpretation of BODE scores might indicate. METHODS: We performed a retrospective analysis of survival according to the BODE score for patients with COPD in the United Network of Organ Sharing (UNOS) database of lung transplantation candidates (n = 4,377) compared with the cohort of patients with COPD in which the BODE score was validated (n = 625). RESULTS: Median survival in the fourth quartile of BODE score was 59 months (95% CI, 51-77 months) in the UNOS cohort and 37 months (95% CI, 29-42 months) in the BODE validation cohort. In models controlling for BODE score and incorporating lung transplantation as a competing end point, the risk of death was higher in the BODE validation cohort (subhazard ratio, 4.8; 95% CI, 4.0-5.7; P < .001). The risk difference was greatest in the fourth quartile of BODE scores (SHR, 6.1; 95% CI, 4.9-7.6; P < .001). CONCLUSIONS: Extrapolation of prognosis based on the BODE score overestimates mortality risk in lung transplantation candidates with COPD. This is likely due to a lower prevalence of comorbid conditions attributable to the lung transplantation evaluation screening process.

Gravity-Drawn Silicone Filaments: Production, Characterization, and Wormlike Chain Dynamics.

We introduce a method to produce continuous polydimethylsiloxane (PDMS) silicone filaments on the order of 0.5 m long and 100 µm in diameter. The approach overcomes traditional limitations in silicone drawing by partially precuring the polymer and drawing through a tube furnace. We characterize the filaments' mechanical properties, and their ability to switch hydrophobicity by UV-ozone and corona discharge patterning. The flexible filaments' dynamic properties were evaluated by way of athermal acoustic excitation at the air-water interface, revealing conformational reconfigurability consistent with a wormlike chain model. We envision applications in rapid prototyping and as a platform for model foldamer studies.

A Novel Large Animal Model of Acute Respiratory Distress Syndrome Induced by Mitochondrial Products.

OBJECTIVE: We aimed to create a reproducible lung injury model utilizing injection of mitochondrial damage-associated molecular products. Our goal was to characterize the pathophysiologic response to damage-associated molecular pattern mediated organ injury. SUMMARY BACKGROUND DATA: There remain significant gaps in our understanding of acute respiratory distress syndrome, in part due to the lack of clinically applicable animal models of this disease. Animal models of noninfectious, tissue damage-induced lung injury are needed to understand the signals and responses associated with this injury. METHODS: Ten pigs (35-45 kg) received an intravenous dose of disrupted mitochondrial products and were followed for 6 hours under general anesthesia. These animals were compared to a control group (n = 5) and a model of lung injury induced by bacterial products (lipopolysaccharide n = 5). RESULTS: Heart rate and temperature were significantly elevated in the mitochondrial product (204 ±â€Š12 and 41 ±â€Š1) and lipopolysaccharide groups (178 ±â€Š18 and 42 ±â€Š0.5) compared with controls (100 ±â€Š13 and 38 ±â€Š0.5) (P <0.05). Lung oxygenation (PaO2/FiO2) was significantly lower 6 hours after injection in the mitochondrial products and lipopolysaccharide groups compared with controls (170 ±â€Š39, 196 ±â€Š27, and 564 ±â€Š75 mm Hg respectively, P = 0.001). Lung injury scoring of histological sections was significantly worse in mitochondrial and lipopolysaccharide groups compared with controls (mitochondrial-64 ±â€Š6, lipopolysaccharide-54 ±â€Š8, control-14 ±â€Š1.5, P= 0.002). CONCLUSIONS: Our data demonstrated that the presence of mitochondrial products in the circulation leads to systemic inflammatory response and lung injury. In its acute phase lung injury induced by tissue or bacterial products is clinically indistinguishable.

The use of extended criteria donors decreases one-year survival in high-risk lung recipients: A review of the United Network of Organ Sharing Database.

OBJECTIVE: The study objective was to investigate the impact of matching donor quality to recipient severity on survival after lung transplant. METHODS: By using the Organ Procurement and Transplantation Network/United Network for Organ Sharing dataset, we analyzed lung transplant recipients from May 4, 2005, to December 31, 2012. By using adjusted Cox regressions, we identified extended criteria donors as those who had 1 or more of the following: age 65 years or more, smoking history of 20 pack-years or more, diabetes mellitus, or African-American race. All other donors were considered standard donors. Recipients were categorized by lung allocation score: lung allocation score less than 70 and lung allocation score 70 or greater. Our primary outcome was 1-year survival after lung transplantation. RESULTS: Of the 10,995 lung recipients, 3792 (34%) received extended criteria donor organs. Extended criteria donors were associated with an increased hazard of death (hazard ratio [HR], 1.41; 95% confidence interval [CI], 1.26-1.56; P < .001). One-year survival was 87% and 82% (P < .001) for recipients with a lung allocation score less than 70 and 80% and 72% (P = .017) for recipients with a lung allocation score 70 or greater who received standard donor and extended criteria donor organs, respectively. In Cox regression models, the hazard of death was increased for recipients with a lung allocation score less than 70 + extended criteria donor (HR, 1.42; 95% CI, 1.27-1.60; P < .001), recipients with a lung allocation score 70 or greater + standard donor (HR, 1.37; 95% CI, 1.10-1.71; P = .005), and was the highest for recipients with a lung allocation score 70 or greater + extended criteria donor (HR, 1.81; 95% CI, 1.40-2.33; P < .001) compared with recipients with a lung allocation score less than 70 + standard donor. CONCLUSIONS: Extended criteria donors are associated with reduced 1-year survival, and recipients with a lung allocation score 70 or greater who receive extended criteria donor organs have the lowest survival.

Rates of intentionally caused and road crash deaths of US citizens abroad.

CONTEXT: Currently, little is known about rates of death by cause and country among US travellers. Understanding the risk by cause and country is imperative to risk communication and the development of risk reduction strategies. METHODS: Publicly available data on non-natural deaths of US citizens abroad were gathered from January 2003 to December 2009 from the US Department of State's Department Bureau of Consular Affairs. Traveller information was gathered from the US Department of Commerce Office of Travel and Tourism for the same time period. Rates of death were calculated by dividing the number of non-natural deaths of US citizens abroad by the number of US outbound visits for each country. RESULTS: A total of 5417 non-natural death events were retrieved between 2003 and 2009 from the US State Department. Intentionally caused death rates ranged from 21.44 per 1 000 000 visits in the Philippines to 0 per 1 000 000 visits in several countries; the majority of countries had fewer than five intentionally caused deaths per 1 000 000 visits. Rates of road traffic crashes were higher than rates of intentionally caused deaths in almost every instance. Thailand had the highest rate of deaths due to road traffic crashes (16.49 per 1 000 000), followed by Vietnam, Morocco and South Africa (15.12 per 1 000 000, 11.96 per 1 000 000 and 10.90 per 1 000 000, respectively). Motorcycle deaths account for most of the heightened risk observed in Thailand and Vietnam. CONCLUSIONS: The leading cause of non-natural deaths in US travellers abroad was road crashes, which exceeds intentional injury as the leading cause of non-natural deaths in almost every country where US citizens travel. Southeast Asia had the highest unintentional injury death rates for US citizens abroad due to the high rates of deaths from motorcycle crashes.

Forcing lateral electron disequilibrium to spare lung tissue: a novel technique for stereotactic body radiation therapy of lung cancer.

Stereotactic body radiation therapy (SBRT) has quickly become a preferred treatment option for early-stage lung cancer patients who are ineligible for surgery. This technique uses tightly conformed megavoltage (MV) x-ray beams to irradiate a tumour with ablative doses in only a few treatment fractions. Small high energy x-ray fields can cause lateral electron disequilibrium (LED) to occur within low density media, which can reduce tumour dose. These dose effects may be challenging to predict using analytic dose calculation algorithms, especially at higher beam energies. As a result, previous authors have suggested using low energy photons (<10 MV) and larger fields (>5 × 5 cm(2)) for lung cancer patients to avoid the negative dosimetric effects of LED. In this work, we propose a new form of SBRT, described as LED-optimized SBRT (LED-SBRT), which utilizes radiotherapy (RT) parameters designed to cause LED to advantage. It will be shown that LED-SBRT creates enhanced dose gradients at the tumour/lung interface, which can be used to manipulate tumour dose, and/or normal lung dose. To demonstrate the potential benefits of LED-SBRT, the DOSXYZnrc (National Research Council of Canada, Ottawa, ON) Monte Carlo (MC) software was used to calculate dose within a cylindrical phantom and a typical lung patient. 6 MV or 18 MV x-ray fields were focused onto a small tumour volume (diameter ∼1 cm). For the phantom, square fields of 1 × 1 cm(2), 3 × 3 cm(2), or 5 × 5 cm(2) were applied. However, in the patient, 3 × 1 cm(2), 3 × 2 cm(2), 3 × 2.5 cm(2), or 3 × 3 cm(2) field sizes were used in simulations to assure target coverage in the superior-inferior direction. To mimic a 180° SBRT arc in the (symmetric) phantom, a single beam profile was calculated, rotated, and beams were summed at 1° segments to accumulate an arc dose distribution. For the patient, a 360° arc was modelled with 36 equally weighted (and spaced) fields focused on the tumour centre. A planning target volume (PTV) was generated by considering the extent of tumour motion over the patient's breathing cycle and set-up uncertainties. All patient dose results were normalized such that at least 95% of the PTV received at least 54 Gy (i.e. D95 = 54 Gy). Further, we introduce 'LED maps' as a novel clinical tool to compare the magnitude of LED resulting from the various SBRT arc plans. Results from the phantom simulation suggest that the best lung sparing occurred for RT parameters that cause severe LED. For equal tumour dose coverage, normal lung dose (2 cm outside the target region) was reduced from 92% to 23%, comparing results between the 18 MV (5 × 5 cm(2)) and 18 MV (1 × 1 cm(2)) arc simulations. In addition to reduced lung dose for the 18 MV (1 × 1 cm(2)) arc, maximal tumour dose increased beyond 125%. Thus, LED can create steep dose gradients to spare normal lung, while increasing tumour dose levels (if desired). In the patient simulation, a LED-optimized arc plan was designed using either 18 MV (3 × 1 cm(2)) or 6 MV (3 × 3cm(2)) beams. Both plans met the D95 dose coverage requirement for the target. However, the LED-optimized plan increased the maximum, mean, and minimum dose within the PTV by as much as 80 Gy, 11 Gy, and 3 Gy, respectively. Despite increased tumour dose levels, the 18 MV (3 × 1 cm(2)) arc plan improved or maintained the V20, V5, and mean lung dose metrics compared to the 6 MV (3 × 3 cm(2)) simulation. We conclude that LED-SBRT has the potential to increase dose gradients, and dose levels within a small lung tumour. The magnitude of tumour dose increase or lung sparing can be optimized through manipulation of RT parameters (e.g. beam energy and field size).

Determinants of influenza vaccine purchasing decision in the US: a conjoint analysis.

We explore the determinants of influenza vaccine purchasing decision in the US via a nationwide survey of 251 medical office managers and physicians on preferences for seven vaccine presentation attributes: price, presence of thimerosal, contamination risk, storage space requirement, number of preparation steps, dosing errors and speed. The findings show that thimerosal, contamination risk, and dosing errors were the most important attributes. For pediatricians, thimerosal's absence was shown to be the most valuable attribute. Participants would be willing to spend the following additional amounts per dose of influenza vaccine to acquire products as follows: $5.06 for the absence of thimerosal, $5.23 for a lower contamination risk, $4.94 for lower chance of dosing errors. They would pay $1.08 more for influenza vaccines that were faster to administer, $1.27 more for vaccines that were easier to store, and $1.76 more for vaccines that had fewer steps to administer.

Skeletal muscle type comparison of pyruvate dehydrogenase phosphatase activity and isoform expression: effects of obesity and endurance training.

Pyruvate dehydrogenase (PDH) plays an important role in regulating carbohydrate metabolism in skeletal muscle. PDH is activated by PDH phosphatase (PDP) and deactivated by PDH kinase (PDK). Obesity has a large negative impact on skeletal muscle carbohydrate metabolism, whereas endurance training has been shown to improve regulatory control of skeletal muscle carbohydrate metabolism, more so when coupled with obesity. A majority of this literature has focused on PDK, with little information available on PDP. To determine the relative role of PDP in regulating skeletal muscle PDH activity with obesity and endurance training, obese and lean Zucker rats remained sedentary or were endurance trained (1 h/day, 5 days/wk) for a period of 8 wk. Soleus, red gastrocnemius, (RG), and white gastrocnemius (WG) muscles were sampled after the training period. The main findings were 1) obesity resulted in a 46% decrease in PDP activity expressed per milligram extracted mitochondrial protein only in RG, while PDP isoform content was unchanged; 2) 8 wk of endurance training led to a significant 1.4-2.2-fold increase in PDP activity of all muscle examined from obese rats, and the concomitant increase in PDP1 protein was only seen in soleus and RG; 3) 8 wk of endurance training led to a trending 1.4-2.2-fold increase in PDP activity of all muscle examined from obese rats, and the concomitant increase in PDP1 protein was only seen in soleus and RG; and 4) PDP2 protein content was not affected by obesity or training. These results suggest that decreased PDP activity in oxidative skeletal muscles may play a role in the impairment of carbohydrate metabolism in obese rats, which is reversible with endurance training.