Evaluating the Climatic and Energy Balance Controls on Snow Accumulation and Melt in Mountain Snowpacks

Snow is indispensible to the water resources and economy of the western United States, making it essential to accurately predict snowmelt volume, timing, and rate. However, uncertainties in snowpack processes, the effects of climate change, and spatial variability in precipitation phase partitioning all complicate efforts to simulate snow accumulation and melt. With those three issues in mind, this work clarifies seasonal snow cover evolution in a changing climate by utilizing ground observations and validated output from a physics-based snow model. The first project focuses on how snowpacks develop cold content, the internal energy deficit that must be satisfied before snowmelt can begin. Previously it was unknown whether cold content developed primarily through meteorological or energy balance processes. Using snow pit data and model output, I show that new snowfall exerts the primary control on cold content development in the snowpacks at an alpine and subalpine site in the Colorado Rocky Mountains. Additionally, model output indicates that cold content damps snowmelt rate and delays snowmelt onset at time scales one month and shorter, but has little correlation to those quantities at seasonal time scales. The second project evaluates the physical processes controlling the response of the alpine and subalpine snowpacks to increases in air temperature and changes to precipitation total and seasonality. The increased sensitivity of the subalpine snowpack to climate warming is primarily a result of decreases to snowpack cold content and increases in positive energy fluxes. As opposed to the differential response to warming, the two snowpacks exhibited fairly consistent responses to changes in total precipitation with later melt onset and faster snowmelt rates being associated with increased precipitation. Changes to precipitation seasonality had a near-negligible impact on snow cover properties at both sites. The final project expands on the spatial scope of the first two by simulating snow accumulation and melt at sites in the western United States that span a climatic gradient from warm maritime to cold continental. Previous research had shown spatial variability in rain-snow partitioning, but little was known about how this variability affected snow model simulations. The results from this project indicate that the selection of a method to partition rain and snow leads to the greatest divergence in seasonal snow cover evolution at the lower elevation maritime sites. Peak snow water equivalent and snowmelt timing simulated by the different methods varied by several hundred millimeters and over one month, respectively, at the warmest sites, and typically less than 20 mm and one week at the two coldest sites. Overall, this dissertation highlights how snow models and ground observations can be used to better understand snow accumulation and melt processes in a changing climate.</p

Protection of ischemic myocardium in dogs using intracoronary 2,3-butanedione monoxime (BDM)

Abstract Background. -Actomyosin ATPase is one of the major ATP consuming enzymes in the myocardium. We tested whether 2,3-butanedione monoxime (BDM), a reversible inhibitor of actomyosin ATPase, given before coronary occlusion, limits infarct size in anesthetized open-chest dogs. Methods and results. -After circumflex artery catheterization using fluoroscopic guidance, BDM (125 mM) or buffer vehicle was infused (12.0 ml/min) for 20 min (BDM-20, n = 5 and Buffer-20, n = 6) or for 5 min (BDM-5, n = 6 and Buffer-5, n = 6) prior to 60 min of ischemia and 3 h of reperfusion. BDM administration increased subendocardial blood flow 271% above baseline flow (radioactive microspheres), and systolic wall thickening was converted to wall bulging (wall thickening by sonomicrometry was -27 ± 29% and -22 ± 13% of baseline in BDM-20 and BDM-5, respectively). Adjusted mean infarct size (% area-at-risk) was 11.0 ± 2.8% and 11.9 ± 2.6% in BDM-20 and BDM-5 vs. 20.2 ± 2.5% and 20.5 ± 2.5% in Buffer-20 and Buffer-5 (ancova, P &lt; 0.05 for each BDM vs. Buffer group). Measurement of glycolytic metabolites and the adenine nucleotide pool of myocardium paced electronically at 150 beats per minute during total ischemia at 37°C following BDM showed a metabolic response similar to that seen in ischemic preconditioning. ATP depletion, nucleoside production, and lactate accumulation were slowed in ischemic tissue treated with BDM. Conclusion. -BDM given before the onset of ischemia markedly limited infarct size and reduced energy demand after the onset of ischemia. The explanation for the reduced infarct size induced by BDM treatment is hypothesized to be the persistent reduction in energy demand found in ischemic BDM treated myocardium

Risk Assessment of Impacts of Climate Change for Key Marine Species in South Eastern Australia. Part 2: species profiles

[Extract] Blacklip and greenlip abalone form the basis of valuable fisheries in Tasmania, Victoria, South Australia and New South Wales (Figure 1.1). The Tasmanian abalone fishery is the largest wild abalone fishery in the world, producing more than 25% of the global catch (Miller et al. 2009). In 2008, the fishery had a gross landed value of $ 90 million. Blacklip abalone (BA), Haliotis rubra, is the predominant species harvested in Tasmania with 2461 t landed in 2008, compared to only 122 t of greenlip abalone (GA), H. laevigata (Tarbath and Gardner 2009). Since 2003, the BA fishery has been divided into five zones: Eastern, Western, Northern, Bass Strait, and Central West (Tarbath and Gardner 2009). The GA fishery is restricted to the north of the state and is managed by regions and separately from the BA fishery. In Victoria, approximately 1,200 t was landed in 2007/08, however, the current TAC is 774 t (2010/11). Catches are dominated by BA (96%) and the fishery is structured into three zones: Western, Central and Eastern. The South Australian fishery harvests approximately 880 t of abalone each year, about 60% of this is BA with the remainder comprising GA. Like Victoria, the South Australian fishery is divided into the Southern, Central and Western zones. Current annual catches in NSW were less than 75 t in 2009/10 and consist exclusively of BA. The commercial fisheries are assessed on a variable combination of commercial catch, effort and size-composition data, fishery-independent surveys and length-structured models. In Tasmania, 105,500 abalone were taken by recreational fishers in 2006/07, weighing an estimated 49 t. The number of recreational licenses has tripled since 1995, with 12,500 recreational diving licenses issued in 2007/08 (Lyle 2008). Recreational catches in SA are small, probably less than 1% of the TACC (Jones, 2009)

Risk Assessment of Impacts of Climate Change for Key Marine Species in South Eastern Australia. Part 2: species profiles

[Extract] Blacklip and greenlip abalone form the basis of valuable fisheries in Tasmania, Victoria, South Australia and New South Wales (Figure 1.1). The Tasmanian abalone fishery is the largest wild abalone fishery in the world, producing more than 25% of the global catch (Miller et al. 2009). In 2008, the fishery had a gross landed value of $ 90 million. Blacklip abalone (BA), Haliotis rubra, is the predominant species harvested in Tasmania with 2461 t landed in 2008, compared to only 122 t of greenlip abalone (GA), H. laevigata (Tarbath and Gardner 2009). Since 2003, the BA fishery has been divided into five zones: Eastern, Western, Northern, Bass Strait, and Central West (Tarbath and Gardner 2009). The GA fishery is restricted to the north of the state and is managed by regions and separately from the BA fishery. In Victoria, approximately 1,200 t was landed in 2007/08, however, the current TAC is 774 t (2010/11). Catches are dominated by BA (96%) and the fishery is structured into three zones: Western, Central and Eastern. The South Australian fishery harvests approximately 880 t of abalone each year, about 60% of this is BA with the remainder comprising GA. Like Victoria, the South Australian fishery is divided into the Southern, Central and Western zones. Current annual catches in NSW were less than 75 t in 2009/10 and consist exclusively of BA. The commercial fisheries are assessed on a variable combination of commercial catch, effort and size-composition data, fishery-independent surveys and length-structured models. In Tasmania, 105,500 abalone were taken by recreational fishers in 2006/07, weighing an estimated 49 t. The number of recreational licenses has tripled since 1995, with 12,500 recreational diving licenses issued in 2007/08 (Lyle 2008). Recreational catches in SA are small, probably less than 1% of the TACC (Jones, 2009)

Integrating data types to estimate spatial patterns of avian migration across the Western Hemisphere

For many avian species, spatial migration patterns remain largely undescribed, especially across hemispheric extents. Recent advancements in tracking technologies and high-resolution species distribution models (i.e., eBird Status and Trends products) provide new insights into migratory bird movements and offer a promising opportunity for integrating independent data sources to describe avian migration. Here, we present a three-stage modeling framework for estimating spatial patterns of avian migration. First, we integrate tracking and band re-encounter data to quantify migratory connectivity, defined as the relative proportions of individuals migrating between breeding and nonbreeding regions. Next, we use estimated connectivity proportions along with eBird occurrence probabilities to produce probabilistic least-cost path (LCP) indices. In a final step, we use generalized additive mixed models (GAMMs) both to evaluate the ability of LCP indices to accurately predict (i.e., as a covariate) observed locations derived from tracking and band re-encounter data sets versus pseudo-absence locations during migratory periods and to create a fully integrated (i.e., eBird occurrence, LCP, and tracking/band re-encounter data) spatial prediction index for mapping species-specific seasonal migrations. To illustrate this approach, we apply this framework to describe seasonal migrations of 12 bird species across the Western Hemisphere during pre- and postbreeding migratory periods (i.e., spring and fall, respectively). We found that including LCP indices with eBird occurrence in GAMMs generally improved the ability to accurately predict observed migratory locations compared to models with eBird occurrence alone. Using three performance metrics, the eBird + LCP model demonstrated equivalent or superior fit relative to the eBird-only model for 22 of 24 species–season GAMMs. In particular, the integrated index filled in spatial gaps for species with over-water movements and those that migrated over land where there were few eBird sightings and, thus, low predictive ability of eBird occurrence probabilities (e.g., Amazonian rainforest in South America). This methodology of combining individual-based seasonal movement data with temporally dynamic species distribution models provides a comprehensive approach to integrating multiple data types to describe broad-scale spatial patterns of animal movement. Further development and customization of this approach will continue to advance knowledge about the full annual cycle and conservation of migratory birds

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570