828 research outputs found
Inventory control for point-of-use locations in hospitals
Most inventory management systems at hospital departments are characterised by lost sales, periodic reviews with short lead times, and limited storage capacity. We develop two types of exact models that deal with all these characteristics. In a capacity model, the service level is maximised subject to a capacity restriction, and in a service model the required capacity is minimised subject to a service level restriction. We also formulate approximation models applicable for any lost-sales inventory system (cost objective, no lead time restrictions etc). For the capacity model, we develop a simple inventory rule to set the reorder levels and order quantities. Numerical results for this inventory rule show an average deviation of 1% from the optimal service levels. We also embed the single-item models in a multi-item system. Furthermore, we compare the performance of fixed order size replenishment policies and (R, s, S) policies
One-Dimensional and Two-Dimensional Simulations of Helical Homopolymers: A Comparative Analysis of Energy Stabilization and Efficiency
The purpose of our work is to analyze the results of a two-dimensional parallel tempering simulation of a coarse-grained helical homopolymer. We aim to measure the efficiency of the simulation and apply this efficiency to the theoretical protein free energy landscape.The stable states for helical homopolymers will be analyzed using the folding funnel theory of free energy landscapes for given polymer configurations. The genesis of each simulation is defined by a randomly configured polymer; as time progresses, the energy of each structure decreases until equilibrium is reached. Data collected after equilibrium is reached is used to understand polymer behavior for each model and simulated temperature. A rolling average algorithm has been designed to establish the time step at which energy stabilization is reached for each model. The simulation is considered to be stable when the rolling average of the energy is within a set fraction of the standard deviation of the rolling window based on the standard deviation and mean of previous windows. Efficiency and equilibration time of the 1D and 2D simulations are compared to determine the value of the two dimensional exchange scheme and analyze the free energy landscape of the polymer configuration
Potentially inappropriate medication in older participants of the Berlin Aging Study II (BASE-II) - Sex differences and associations with morbidity and medication use
INTRODUCTION:
Multimorbidity in advanced age and the need for drug treatment may lead to polypharmacy, while pharmacokinetic and pharmacodynamic changes may increase the risk of adverse drug events (ADEs).
OBJECTIVE:
The aim of this study was to determine the proportion of subjects using potentially inappropriate medication (PIM) in a cohort of older and predominantly healthy adults in relation to polypharmacy and morbidity.
METHODS:
Cross-sectional data were available from 1,382 study participants (median age 69 years, IQR 67-71, 51.3% females) of the Berlin Aging Study II (BASE-II). PIM was classified according to the EU(7)-PIM and German PRISCUS (representing a subset of the former) list. Polypharmacy was defined as the concomitant use of at least five drugs. A morbidity index (MI) largely based on the Charlson Index was applied to evaluate the morbidity burden.
RESULTS:
Overall, 24.1% of the participants were affected by polypharmacy. On average, men used 2 (IQR 1-4) and women 3 drugs (IQR 1-5). According to PRISCUS and EU(7)-PIM, 5.9% and 22.6% of participants received at least one PIM, while use was significantly more prevalent in females (25.5%) compared to males (19.6%) considering EU(7)-PIM (p = 0.01). In addition, morbidity in males receiving PIM according to EU(7)-PIM was higher (median MI 1, IQR 1-3) compared to males without PIM use (median MI 1, IQR 0-2, p<0.001).
CONCLUSION:
PIM use occurred more frequently in women than in men, while it was associated with higher morbidity in males. As expected, EU(7)-PIM identifies more subjects as PIM users than the PRISCUS list but further studies are needed to investigate the differential impact of both lists on ADEs and outcome.
KEY POINTS:
We found PIM use to be associated with a higher number of regular medications and with increased morbidity. Additionally, we detected a higher prevalence of PIM use in females compared to males, suggesting that women and people needing intensive drug treatment are patient groups, who are particularly affected by PIM use
MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment
Rather than targeting tumour cells directly, elements of the tumour microenvironment can be modulated to sensitize tumours to the effects of therapy. Here we report a unique mechanism by which ectopic microRNA-103 can manipulate tumour-associated endothelial cells to enhance tumour cell death. Using gain-and-loss of function approaches, we show that miR-103 exacerbates DNA damage and inhibits angiogenesis in vitro and in vivo. Local, systemic or vascular-targeted delivery of miR-103 in tumour-bearing mice decreased angiogenesis and tumour growth. Mechanistically, miR-103 regulation of its target gene TREX1 in endothelial cells governs the secretion of pro-inflammatory cytokines into the tumour microenvironment. Our data suggest that this inflammatory milieu may potentiate tumour cell death by supporting immune activation and inducing tumour expression of Fas and TRAIL receptors. Our findings reveal miR-mediated crosstalk between vasculature and tumour cells that can be exploited to improve the efficacy of chemotherapy and radiation.United States. National Institutes of Health (R00HL112962)United States. National Institutes of Health (R01 HL57900)Oregon Health & Science University. Knight Cancer Institute (2015-Dive-Knight-01
What the papers say: Text mining for genomics and systems biology
Keeping up with the rapidly growing literature has become virtually impossible for most scientists. This can have dire consequences. First, we may waste research time and resources on reinventing the wheel simply because we can no longer maintain a reliable grasp on the published literature. Second, and perhaps more detrimental, judicious (or serendipitous) combination of knowledge from different scientific disciplines, which would require following disparate and distinct research literatures, is rapidly becoming impossible for even the most ardent readers of research publications. Text mining -- the automated extraction of information from (electronically) published sources -- could potentially fulfil an important role -- but only if we know how to harness its strengths and overcome its weaknesses. As we do not expect that the rate at which scientific results are published will decrease, text mining tools are now becoming essential in order to cope with, and derive maximum benefit from, this information explosion. In genomics, this is particularly pressing as more and more rare disease-causing variants are found and need to be understood. Not being conversant with this technology may put scientists and biomedical regulators at a severe disadvantage. In this review, we introduce the basic concepts underlying modern text mining and its applications in genomics and systems biology. We hope that this review will serve three purposes: (i) to provide a timely and useful overview of the current status of this field, including a survey of present challenges; (ii) to enable researchers to decide how and when to apply text mining tools in their own research; and (iii) to highlight how the research communities in genomics and systems biology can help to make text mining from biomedical abstracts and texts more straightforward
Reconstruction of primary vertices at the ATLAS experiment in Run 1 proton–proton collisions at the LHC
This paper presents the method and performance of primary vertex reconstruction in proton–proton collision data recorded by the ATLAS experiment during Run 1 of the LHC. The studies presented focus on data taken during 2012 at a centre-of-mass energy of √s=8 TeV. The performance has been measured as a function of the number of interactions per bunch crossing over a wide range, from one to seventy. The measurement of the position and size of the luminous region and its use as a constraint to improve the primary vertex resolution are discussed. A longitudinal vertex position resolution of about 30μm is achieved for events with high multiplicity of reconstructed tracks. The transverse position resolution is better than 20μm and is dominated by the precision on the size of the luminous region. An analytical model is proposed to describe the primary vertex reconstruction efficiency as a function of the number of interactions per bunch crossing and of the longitudinal size of the luminous region. Agreement between the data and the predictions of this model is better than 3% up to seventy interactions per bunch crossing
Effects of Bolus vs. Metered Rehydration Rates on Fluid Retention and Hydration Efficiency using 150% Fluid Replacement.
Effects of Bolus vs. Metered Rehydration Rates on Fluid Retention and Hydration Efficiency using 150% Fluid Replacement. Authors: Jared Graham (Masters), Tiffany Newcomb (Masters), Nathan Frischman (Undergraduate), Eric Jones (Ph D) Department of Kinesiology and Health Science Stephen F. Austin State University Nacogdoches TX. 75962 Purpose: This study assessed differences in urine production using bolus vs. metered ingestion fluid consumption during post-exercise rehydration. Methods: Using light to moderate activity in an environmentally controlled chamber (35°C), 9 male subjects were dehydrated by ~ 2% body weight. Following dehydration, counterbalanced rehydration trials (water) were performed in which two different methods of rehydrating; metered consumption (18.75% of total volume every 30mins for 4 hours) and bolus consumption (150% of total volume within 1 hour) were utilized. Urine production was evaluated and reported each hour during an eight-hour period following exercise to evaluate net fluid balance and hydration efficiency (fluid consumed vs. fluid retained). Results: Paired samples T-test revealed no significant differences (p=.94) between the two rehydration methods for hydration efficiency (bolus 41.5% vs. metered 42%) or net fluid balance (mean urine production: bolus 1347ml vs. metered 1337ml). Conclusions: Previous research using 100% fluid replacement (water) has revealed that metered consumption improves hydration efficiency and net fluid balance. However, the current findings suggest that any advantages gained through varying fluid consumption rates may be nullified by larger total rehydration volumes (150%)
The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review.
BACKGROUND: The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects. This review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous. SHORT CONCLUSIONS: This review offers a comprehensive assessment of the evidence behind the translation of basic science to the clinical practice of cartilage repair. It has revealed a lack of connectivity between the in vitro, pre-clinical and human data and a patchwork quilt of synergistic evidence. Drivers for progress in this space are largely driven by patient demand, surgeon inquisition and a regulatory framework that is learning at the same pace as new developments take place
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