A Model to Create an Efficient and Equitable Admission Policy for Patients Arriving to the Cardiothoracic ICU

To develop queuing and simulation-based models to understand the relationship between ICU bed availability and operating room schedule to maximize the use of critical care resources and minimize case cancellation while providing equity to patients and surgeons. Queuing theory and computer simulation can be used to model case flow through a cardiothoracic operating room and ICU. A dynamic admission policy that looks at current waiting time and expected ICU length of stay allows for increased equity between patients with only minimum losses of efficiency. This dynamic admission policy would seem to be a superior in maximizing case-flow. These results may be generalized to other surgical ICUs

Inefficiency as the major driver of excess costs in lung resection

BackgroundRisk-adjusted outcomes of surgical care are important for quality and cost assessments. Although cardiac surgery is commonly studied, risk-adjusted analysis of excess costs of lung resection has not been pursued.MethodsWe used 2002 to 2005 National Inpatient Sample of the Healthcare Cost and Utilization Project data to evaluate adverse outcomes and costs in elective lung resections in hospitals with more than 20 cases during that period. Adverse outcomes were inpatient death or excessive risk-adjusted postoperative stay. Logistic models were defined to predict adverse outcomes. Linear models were designed to predict costs. Hospital-specific adverse outcome rates and costs were measured to define performance outliers. Cost-effective reference hospitals were used to define total excess costs.ResultsAmong 12,182 patients at 215 hospitals undergoing lung resection, there were 336 inpatient deaths (2.8%) and 880 live discharges with prolonged risk-adjusted postoperative stay (7.2%). Predictive models for mortality and risk-adjusted postoperative stay had C statistics of 0.773 and 0.643, respectively. There were 11 ineffective hospitals (5.1%) with excessive adverse outcomes (P < .005) and 34 inefficient hospitals (15.8%) meeting quality measures but with higher than predicted costs (P < .0005). Ineffective hospitals had costs $1020 per case lower than predicted. Inefficient hospitals had costs$9978 higher than predicted.ConclusionsInefficiency is the major factor in excess inpatient costs associated with lung resection in this model. Although refinements in databases, including total physician costs and postdischarge adverse event costs, will alter models, excess costs of lung resection appear to be driven by inefficiency, not adverse outcomes

Simulation of reaction diffusion processes over biologically relevant size and time scales using multi-GPU workstations

AbstractSimulation of in vivo cellular processes with the reaction–diffusion master equation (RDME) is a computationally expensive task. Our previous software enabled simulation of inhomogeneous biochemical systems for small bacteria over long time scales using the MPD-RDME method on a single GPU. Simulations of larger eukaryotic systems exceed the on-board memory capacity of individual GPUs, and long time simulations of modest-sized cells such as yeast are impractical on a single GPU. We present a new multi-GPU parallel implementation of the MPD-RDME method based on a spatial decomposition approach that supports dynamic load balancing for workstations containing GPUs of varying performance and memory capacity. We take advantage of high-performance features of CUDA for peer-to-peer GPU memory transfers and evaluate the performance of our algorithms on state-of-the-art GPU devices. We present parallel efficiency and performance results for simulations using multiple GPUs as system size, particle counts, and number of reactions grow. We also demonstrate multi-GPU performance in simulations of the Min protein system in E. coli. Moreover, our multi-GPU decomposition and load balancing approach can be generalized to other lattice-based problems

Endocrine responses and acute mTOR pathway phosphorylation to resistance exercise with leucine and whey

Leucine ingestion reportedly activates the mTOR pathway in skeletal muscle, contributing to a hypertrophy response. The purpose of the study was to compare the post-resistance exercise effects of leucine and whey protein supplementation on endocrine responses and muscle mTOR pathway phosphorylation. On visit 1, subjects (X±SD; n=20; age=27.8±2.8yrs) provided baseline blood samples for analysis of cortisol, glucose and insulin; a muscle biopsy of the vastus lateralis muscle to assess mTOR signaling pathway phosphorylation; and were tested for maximum strength on the leg press and leg extension exercises. For visits 2 and 3, subjects were randomized in a double-blind crossover design to ingest either leucine and whey protein (10g+10g; supplement) or a non-caloric placebo. During these visits, 5 sets of 10 repetitions were performed on both exercises, immediately followed by ingestion of the supplement or placebo. Blood was sampled 30 min post-, and a muscle biopsy 45 min post-exercise. Western blots quantified total and phosphorylated proteins. Insulin increased (α<.05) with supplementation with no change in glucose compared to placebo. Relative phosphorylation of AKT and rpS6 were greater with leucine and whey supplementation compared to placebo. Supplementation of leucine and whey protein immediately after heavy resistance exercise increases anabolic signaling in human skeletal muscle

Computational Design and Elaboration of a De Novo Heterotetrameric α-Helical Protein that Selectively Binds an Emissive Abiological (Porphinato)zinc Chromophore

The first example of a computationally de novo designed protein that binds an emissive abiological chromophore is presented, in which a sophisticated level of cofactor discrimination is pre-engineered. This heterotetrameric, C(2)-symmetric bundle, A(His):B(Thr), uniquely binds (5,15-di[(4-carboxymethyleneoxy)phenyl]porphinato)zinc [(DPP)Zn] via histidine coordination and complementary noncovalent interactions. The A(2)B(2) heterotetrameric protein reflects ligand-directed elements of both positive and negative design, including hydrogen bonds to second-shell ligands. Experimental support for the appropriate formulation of [(DPP)Zn:A(His):B(Thr)](2) is provided by UV/visible and circular dichroism spectroscopies, size exclusion chromatography, and analytical ultracentrifugation. Time-resolved transient absorption and fluorescence spectroscopic data reveal classic excited-state singlet and triplet PZn photophysics for the A(His):B(Thr):(DPP)Zn protein (k(fluorescence) = 4 x 10(8) s(-1); tau(triplet) = 5 ms). The A(2)B(2) apoprotein has immeasurably low binding affinities for related [porphinato]metal chromophores that include a (DPP)Fe(III) cofactor and the zinc metal ion hemin derivative [(PPIX)Zn], underscoring the exquisite active-site binding discrimination realized in this computationally designed protein. Importantly, elements of design in the A(His):B(Thr) protein ensure that interactions within the tetra-alpha-helical bundle are such that only the heterotetramer is stable in solution; corresponding homomeric bundles present unfavorable ligand-binding environments and thus preclude protein structural rearrangements that could lead to binding of (porphinato)iron cofactors

Changing the Custody of Children Whose Parents Have Been Divorced: A General View of the Process

The purpose of this project was to obtain a preliminary description, through study of the legal files, of that group of persons who appear before the Court of Domestic Relations for a reconsideration of the custody decision made initially, at the time of divorce. A sample of 92 cases heard in Multnomah County in 1965 was obtained. A survey of the literature revealed that much of what has been written on the subject of divorce and custody is primarily from a statistical or legalistic standpoint and very little bears directly on the granting or obtaining of custody or the problems encountered by the custodial or non-custodial parents and the children. A reading schedule was developed for the purpose of recording the information in the legal files maintained by the court. The characteristics of the sample group were tallied in an effort to obtain a statistical profile of that group requiring additional court appearances to settle the matter of custody. A number of hypotheses were developed and tested by means of Chi Square. Though this study was limited by the fact that no control group was used and no personal interviews were obtained, it clearly indicates the need for additional research in the area of divorce and custody and suggestions are made for future projects

Effect of a liquid multi-vitamin-mineral supplement on anaerobic exercise performance

This is the publisher's version, also found at http://ehis.ebscohost.com/ehost/detail?sid=10f44d64-ddff-470e-a85a-b4c63b016efa%40sessionmgr10&vid=1&hid=2&bdata=JnNpdGU9ZWhvc3QtbGl2ZQ%3d%3d#db=s3h&AN=20338872The purpose of this study was to determine if supplementation with a liquid multi-vitamin/mineral would improve anaerobic exercise performance. Fourteen resistance-trained men performed a 30-second cycle sprint and one set of squat exercise on 2 separate days before and following 8 weeks of supplementation with either a liquid multi-vitamin/ mineral or a placebo. Heart rate, perceived exertion, blood lactate, peak and mean power, and rate of fatigue were determined for all tests. No differences were noted for any variable (P > 0.05). When controlling for presupplementation values, however, a decreased rate of fatigue was noted for both exercise tests following the multi-vitamin/mineral supplementation. These data suggest that in resistance trained men consuming a nutritionally sound diet, supplementation with a liquid multi-vitamin/mineral does not favorably impact most anaerobic exercise performances. Such supplementation, however, may result in a minor decreased rate of fatigue. It appears that, in terms of improved short duration anaerobic exercise performance, supplemental micronutrients may not be efficient ergogenic agents for well-trained individuals consuming an adequate diet

Ibrutinib inhibits platelet integrin αIIbβ3 outside-in signaling and thrombus stability but not adhesion to collagen

OBJECTIVE: Ibrutinib is an irreversible Bruton tyrosine kinase inhibitor approved for treatment of Waldenstrom macroglobulinemia, chronic lymphocytic leukemia, and mantle cell lymphoma that increases the risk of bleeding among patients. Platelets from ibrutinib-treated patients exhibit deficiencies in collagen-evoked signaling in suspension; however, the significance of this observation and how it relates to bleeding risk is unclear, as platelets encounter immobile collagen in vivo. We sought to clarify the effects of ibrutinib on platelet function to better understand the mechanism underlying bleeding risk. APPROACH AND RESULTS: By comparing signaling in suspension and during adhesion to immobilized ligands, we found that the collagen signaling deficiency caused by ibrutinib is milder during adhesion to immobilized collagen. We also found that platelets in whole blood treated with ibrutinib adhered to collagen under arterial shear but formed unstable thrombi, suggesting that the collagen signaling deficiency caused by ibrutinib may not be the predominant cause of bleeding in vivo. However, clot retraction and signaling evoked by platelet adhesion to immobilized fibrinogen were also inhibited by ibrutinib, indicating that integrin αIIbβ3 outside-in signaling is also effected in addition to GPVI signaling. When ibrutinib was combined with the P2Y12 inhibitor, cangrelor, thrombus formation under arterial shear was inhibited additively. CONCLUSIONS: These findings suggest that (1) ibrutinib causes GPVI and integrin αIIbβ3 platelet signaling deficiencies that result in formation of unstable thrombi and may contribute toward bleeding observed in vivo and (2) combining ibrutinib with P2Y12 antagonists, which also inhibit thrombus stability, may have a detrimental effect on hemostasis

Endocrine responses to overreaching before and after 1 year of weightlifting

This is the publisher's version, also found at http://ehis.ebscohost.com/ehost/external?sid=c58e4c93-cdad-411e-8971-ff871436da4b%40sessionmgr14&vid=3&hid=1

The DNA-damage signature in Saccharomyces cerevisiae is associated with single-strand breaks in DNA

BACKGROUND: Upon exposure to agents that damage DNA, Saccharomyces cerevisiae undergo widespread reprogramming of gene expression. Such a vast response may be due not only to damage to DNA but also damage to proteins, RNA, and lipids. Here the transcriptional response of S. cerevisiae specifically induced by DNA damage was discerned by exposing S. cerevisiae to a panel of three "radiomimetic" enediyne antibiotics (calicheamicin γ(1)(I), esperamicin A1 and neocarzinostatin) that bind specifically to DNA and generate varying proportions of single- and double-strand DNA breaks. The genome-wide responses were compared to those induced by the non-selective oxidant γ-radiation. RESULTS: Given well-controlled exposures that resulted in similar and minimal cell death (~20–25%) across all conditions, the extent of gene expression modulation was markedly different depending on treatment with the enediynes or γ-radiation. Exposure to γ-radiation resulted in more extensive transcriptional changes classified both by the number of genes modulated and the magnitude of change. Common biological responses were identified between the enediynes and γ-radiation, with the induction of DNA repair and stress response genes, and the repression of ribosomal biogenesis genes. Despite these common responses, a fraction of the response induced by gamma radiation was repressed by the enediynes and vise versa, suggesting that the enediyne response is not entirely "radiomimetic." Regression analysis identified 55 transcripts with gene expression induction associated both with double- or single-strand break formation. The S. cerevisiae "DNA damage signature" genes as defined by Gasch et al. [1] were enriched among regulated transcripts associated with single-strand breaks, while genes involved in cell cycle regulation were associated with double-strand breaks. CONCLUSION: Dissection of the transcriptional response in yeast that is specifically signaled by DNA strand breaks has identified that single-strand breaks provide the signal for activation of transcripts encoding proteins involved in the DNA damage signature in S. cerevisiae, and double-strand breaks signal changes in cell cycle regulation genes