1,525 research outputs found
Life Planning / Strategic Planning / Financial Planning
This Paper examines a technique for doing ‘Life Planning’. The technique is one that has been tested by the author in a number of sections of a business school’s capstone course. The study is empirical in nature, applying concepts found, mainly, in strategic planning but, also in psychology, career planning and financial planning
What Have I Learned?
Peter Caswell had always viewed the families bottling business as his birthright. He was stunned when his father sold the business while he was still in college. After becoming a successful personal injury lawyer with a bright future, he learns of the Brustlin Bottling Company that was for sale. In the case Peter reviews with Alan Dawes, his long time friend, information he has developed on five successful companies in the boutique soft drink bottling business. He is trying to decide his next steps a strategy to employ in the business
Transfer Pricing In Transnational Operations: A Case- And Literature-Based Analysis
This paper represents a combined case- and literature-based analysis of transnational pricing and highlights the difference in the issues and perspectives of the business and academic environments. Following an introduction to the issue (noting the growing importance of the transfer of goods from one organizational entity to another within a multinational firm), a short case - The Henderson Company - illustrates how a relatively simple announcement can lead to a lengthy and heated discussion that points out the differences in opinion both between the headquarters and the subsidiaries and between the various regional entities themselves. The analysis of the case reflecting the concerns and perspectives of the members of the international management team (in terms of involvement and partnership, legal and operational concerns, competitive marketing strategy, and evaluation, compensation, and motivational issues) is followed by a literature-based analysis that looks at the complexities of the situation in terms of management, economics, taxation, and finance research. The paper concludes with the recognition that the issue of transnational pricing is a complex one that needs to be addressed from both an organizational perspective and from an international viewpoint emphasizing the development of ways of more accurately reflecting cost allocations
Changes in hospital mortality for United States intensive care unit admissions from 1988 to 2012
Introduction
A decrease in disease-specific mortality over the last twenty years has been reported for patients admitted to United States (US) hospitals, but data for intensive care patients are lacking. The aim of this study was to describe changes in hospital mortality and case-mix using clinical data for patients admitted to multiple US ICUs over the last 24 years. Methods
We carried out a retrospective time series analysis of hospital mortality using clinical data collected from 1988 to 2012. We also examined the impact of ICU admission diagnosis and other clinical characteristics on mortality over time. The potential impact of hospital discharge destination on mortality was also assessed using data from 2001 to 2012. Results
For 482,601 ICU admissions there was a 35% relative decrease in mortality from 1988 to 2012 despite an increase in age and severity of illness. This decrease varied greatly by diagnosis. Mortality fell by \u3e60% for patients with chronic obstructive pulmonary disease, seizures and surgery for aortic dissection and subarachnoid hemorrhage. Mortality fell by 51% to 59% for six diagnoses, 41% to 50% for seven diagnoses, and 10% to 40% for seven diagnoses. The decrease in mortality from 2001 to 2012 was accompanied by an increase in discharge to post-acute care facilities and a decrease in discharge to home. Conclusions
Hospital mortality for patients admitted to US ICUs has decreased significantly over the past two decades despite an increase in the severity of illness. Decreases in mortality were diagnosis specific and appear attributable to improvements in the quality of care, but changes in discharge destination and other confounders may also be responsible
Lessons from LIMK1 enzymology and their impact on inhibitor design
LIM domain kinase 1 (LIMK1) is a key regulator of actin dynamics. It is thereby a potential therapeutic target for the prevention of fragile X syndrome and amyotrophic lateral sclerosis. Herein, we use X-ray crystallography and activity assays to describe how LIMK1 accomplishes substrate specificity, to suggest a unique ‘rock-and-poke’ mechanism of catalysis and to explore the regulation of the kinase by activation loop phosphorylation. Based on these findings, a differential scanning fluorimetry assay and a RapidFire mass spectrometry activity assay were established, leading to the discovery and confirmation of a set of small-molecule LIMK1 inhibitors. Interestingly, several of the inhibitors were inactive towards the closely related isoform LIMK2. Finally, crystal structures of the LIMK1 kinase domain in complex with inhibitors (PF-477736 and staurosporine, respectively) are presented, providing insights into LIMK1 plasticity upon inhibitor binding
Aspects of topology of condensates and knotted solitons in condensed matter systems
The knotted solitons introduced by Faddeev and Niemi is presently a subject
of great interest in particle and mathematical physics. In this paper we give a
condensed matter interpretation of the recent results of Faddeev and Niemi.Comment: v2: Added a reference to the paper E. Babaev, L.D. Faddeev and A.J.
Niemi cond-mat/0106152 where an exact equivalence was shown between the
two-condensate Ginzburg-Landau model and a version of Faddeev model.
Miscelaneous links related to knotted solitons are available at the author
homepage at http://www.teorfys.uu.se/PEOPLE/egor/ . Animations of knotted
solitons by Hietarinta and Salo are available at
http://users.utu.fi/h/hietarin/knots/c45_p2.mp
In Vitro Anti-Hepatitis B Virus Activities of 5’-O-Myristoyl Analogue Derivatives of 3’-Fluoro-2’,3’-dideoxythymidine (FLT) and 3’-Azido-2’,3’- dideoxythymidine (AZT)
Purpose: The objective of this study was to evaluate a dual action prodrug concept wherein an unnatural myristic acid analogue is coupled via an ester moiety to the 5’-position of FLT or AZT. Subsequent intracellular cleavage of the prodrug ester would simultaneously release FLT or AZT that could inhibit reverse transcriptase (RT), and the myristic acid analogue that could inhibit myristoyl- CoA:protein N-myristoyltransferase (NMT).
Methods: Cytotoxicity (2.2.15 cell culture), and antihepatitis B activity of 5’-O-myristoyl analogue prodrug derivatives of FLT and AZT (2-8) were evaluated in vitro using human liver hepatitis B virus (HBV) producing 2.2.15 cell lines.
Results: The 5’- O-(12-methoxydodecanoyl) ester derivatives of AZT (2, EC50 = 2.7 ± 0.3 mM; CC50 = 727 ± 19 μM) and FLT (4, EC50 = 2.8 ± 0.3 μM; CC50 = 186 ± 20 μM) were the most effective anti-hepatitis B virus (anti-HBV) compounds of this series in a replication assay. In the series of 5’-O-myristic acid analogue ester prodrug derivatives of FLT, the relative anti-HBV potency order was MeO(CH2)11CO2- \u3e N3(CH2)11CO2- and Br(CH2)11CO2- \u3e EtS(CH2)nCO2-(n = 10 or 11) \u3e Me(CH2)12CO2- (myristoyl).
Conclusions: The in vitro data suggest that the 5’-Omyristoyl analogue prodrug concept offers a potential drug design approach to design dual acting antiiviral agents, with superior pharmacokinetic, biodistribution, reduced cytotoxicity and/or increased efficacy. In this regard, the 5’-O-(12-methoxydodecanoyl) prodrug ester of 3’-thia-3’-deoxythymidine (3TC) may offer the greatest potential for the treatment of HBV infection
A comparison between the APACHE II and Charlson Index Score for predicting hospital mortality in critically ill patients
<p>Abstract</p> <p>Background</p> <p>Risk adjustment and mortality prediction in studies of critical care are usually performed using acuity of illness scores, such as Acute Physiology and Chronic Health Evaluation II (APACHE II), which emphasize physiological derangement. Common risk adjustment systems used in administrative datasets, like the Charlson index, are entirely based on the presence of co-morbid illnesses. The purpose of this study was to compare the discriminative ability of the Charlson index to the APACHE II in predicting hospital mortality in adult multisystem ICU patients.</p> <p>Methods</p> <p>This was a population-based cohort design. The study sample consisted of adult (>17 years of age) residents of the Calgary Health Region admitted to a multisystem ICU between April 2002 and March 2004. Clinical data were collected prospectively and linked to hospital outcome data. Multiple regression analyses were used to compare the performance of APACHE II and the Charlson index.</p> <p>Results</p> <p>The Charlson index was a poor predictor of mortality (C = 0.626). There was minimal difference between a baseline model containing age, sex and acute physiology score (C = 0.74) and models containing either chronic health points (C = 0.76) or Charlson index variations (C = 0.75, 0.76, 0.77). No important improvement in prediction occurred when the Charlson index was added to the full APACHE II model (C = 0.808 to C = 0.813).</p> <p>Conclusion</p> <p>The Charlson index does not perform as well as the APACHE II in predicting hospital mortality in ICU patients. However, when acuity of illness scores are unavailable or are not recorded in a standard way, the Charlson index might be considered as an alternative method of risk adjustment and therefore facilitate comparisons between intensive care units.</p
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