Why and how does shared language affect subsidiary knowledge inflows? A social identity perspective

We draw on social identity theory to conceptualize a moderated mediation model that examines the relationship between shared language among subsidiary and HQ managers, and subsidiaries’ knowledge inflows from HQ. Specifically, we study (1) whether this relationship is mediated by the extent to which subsidiary managers share HQ goals and vision, and the extent to which HR decisions are centralized; and (2) whether subsidiary type moderates these mediated relationships. Building on a sample of 817 subsidiaries in nine countries/regions, we find support for our model. Implications for research on HQ-subsidiary knowledge flows, social identity theory and international HRM are discussed

Phase I and pharmacokinetic study of XR11576, an oral topoisomerase I and II inhibitor, administered on days 1–5 of a 3-weekly cycle in patients with advanced solid tumours

XR11576 is an oral topoisomerase I and II inhibitor. The objectives of this phase I study were to assess the dose-limiting toxicities (DLTs), to determine the maximum tolerated dose (MTD) and to describe the pharmacokinetics (PKs) of XR11576 when administered orally on days 1-5 every 3 weeks to patients with advanced solid tumours. Patients were treated with escalating doses of XR11576 at doses ranging from 30

Clinical chronobiology: a timely consideration in critical care medicine

A fundamental aspect of human physiology is its cyclical nature over a 24-h period, a feature conserved across most life on Earth. Organisms compartmentalise processes with respect to time in order to promote survival, in a manner that mirrors the rotation of the planet and accompanying diurnal cycles of light and darkness. The influence of circadian rhythms can no longer be overlooked in clinical settings; this review provides intensivists with an up-to-date understanding of the burgeoning field of chronobiology, and suggests ways to incorporate these concepts into daily practice to improve patient outcomes. We outline the function of molecular clocks in remote tissues, which adjust cellular and global physiological function according to the time of day, and the potential clinical advantages to keeping in time with them. We highlight the consequences of "chronopathology", when this harmony is lost, and the risk factors for this condition in critically ill patients. We introduce the concept of "chronofitness" as a new target in the treatment of critical illness: preserving the internal synchronisation of clocks in different tissues, as well as external synchronisation with the environment. We describe methods for monitoring circadian rhythms in a clinical setting, and how this technology may be used for identifying optimal time windows for interventions, or to alert the physician to a critical deterioration of circadian rhythmicity. We suggest a chronobiological approach to critical illness, involving multicomponent strategies to promote chronofitness (chronobundles), and further investment in the development of personalised, time-based treatment for critically ill patients

A transcriptomal analysis of bovine oviductal epithelial cells collected during the follicular phase versus the luteal phase of the estrous cycle

BACKGROUND: Reproductive success depends on a functional oviduct for gamete storage, maturation, fertilization, and early embryonic development. The ovarian-derived steroids estrogen and progesterone are key regulators of oviductal function. The objective of this study was to investigate luteal and follicular phase-specific oviductal epithelial cell function by using microarray-based transcriptional profiling, to increase our understanding of mRNAs regulating epithelial cell processes, and to identify novel genes and biochemical pathways that may be found to affect fertility in the future. METHODS: Six normally cycling Angus heifers were assigned to either luteal phase (LP, n = 3) or follicular phase (FP, n = 3) treatment groups. Heifers in the LP group were killed between day 11 and 12 after estrus. Heifers in the FP group were treated with 25 mg PGF(2α) (Lutalyse, Pfizer, NY) at 8 pm on day 6 after estrus and killed 36 h later. Transcriptional profiling by microarray and confirmation of selected mRNAs by real-time RT-PCR analyses was performed using total RNA from epithelial cells isolated from sections of the ampulla and isthmus collected from LP and FP treatment groups. Differentially expressed genes were subjected to gene ontology classification and bioinformatic pathway analyses. RESULTS: Statistical one-way ANOVA using Benjamini-hochberg multiple testing correction for false discovery rate (FDR) and pairwise comparison of epithelial cells in the ampulla of FP versus LP groups revealed 972 and 597 transcripts up- and down-regulated, respectively (P < 0.05). Within epithelial cells of the isthmus in FP versus LP groups, 946 and 817 transcripts were up- and down-regulated, respectively (P < 0.05). Up-regulated genes from both ampulla and isthmus were found to be largely involved in cholesterol biosynthesis and cell cycle pathways, while down-regulated genes were found in numerous inflammatory response pathways. CONCLUSIONS: Microarray-based transcriptional profiling revealed phase of the cycle-dependent changes in the expression of mRNA within the epithelium of the oviducts’ ampulla and isthmus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12958-015-0077-1) contains supplementary material, which is available to authorized users

Prevention of acute kidney injury and protection of renal function in the intensive care unit

Acute renal failure on the intensive care unit is associated with significant mortality and morbidity. To determine recommendations for the prevention of acute kidney injury (AKI), focusing on the role of potential preventative maneuvers including volume expansion, diuretics, use of inotropes, vasopressors/vasodilators, hormonal interventions, nutrition, and extracorporeal techniques. A systematic search of the literature was performed for studies using these potential protective agents in adult patients at risk for acute renal failure/kidney injury between 1966 and 2009. The following clinical conditions were considered: major surgery, critical illness, sepsis, shock, and use of potentially nephrotoxic drugs and radiocontrast media. Where possible the following endpoints were extracted: creatinine clearance, glomerular filtration rate, increase in serum creatinine, urine output, and markers of tubular injury. Clinical endpoints included the need for renal replacement therapy, length of stay, and mortality. Studies are graded according to the international Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) group system Several measures are recommended, though none carries grade 1A. We recommend prompt resuscitation of the circulation with special attention to providing adequate hydration whilst avoiding high-molecular-weight hydroxy-ethyl starch (HES) preparations, maintaining adequate blood pressure using vasopressors in vasodilatory shock. We suggest using vasopressors in vasodilatory hypotension, specific vasodilators under strict hemodynamic control, sodium bicarbonate for emergency procedures administering contrast media, and periprocedural hemofiltration in severe chronic renal insufficiency undergoing coronary intervention

Incorporating ulipristal acetate in the care of symptomatic uterine fibroids: a Canadian cost-utility analysis of pharmacotherapy management

Bernice Tsoi,1,2 Gord Blackhouse,1,2 Simon Ferrazzi,3 Clare J Reade,4 Innie Chen,5,6 Ron Goeree1,2,7 1Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada; 2Programs for Assessment of Technology in Health (PATH) Research Institute, St Joseph&#39;s Healthcare Hamilton, Hamilton, ON, Canada; 3Independent Consultant, Oakville, ON, Canada; 4Division of Gynecologic Oncology, University of Toronto, Toronto, ON, Canada; 5Department of Obstetrics and Gynaecology, University of Ottawa, 6Ottawa Hospital Research Institute, Ottawa, ON, Canada; 7Centre for Evaluation of Medicines (CEM), St Joseph&#39;s Healthcare Hamilton, Hamilton, ON, Canada Objective: To present a Canadian economic evaluation on the cost-utility of ulipristal acetate (5 mg orally daily) compared to leuprolide acetate (3.75 mg intramuscular monthly) in the treatment of moderate-to-severe symptoms of uterine fibroids in women eligible for surgery. Methods: A probabilistic decision tree was constructed to model the pre-operative pharmacological management of uterine fibroids under the primary perspective of the Ontario public payer. The model parameterized data from clinical trials, observational studies, and public costing databases. The outcome measure was the incremental cost-utility ratio. Uncertainty in the model was explored through sensitivity and scenario analyses. Results: Ulipristal was associated with faster control of excessive menstrual bleeding, fewer symptoms of hot flashes and lower health care resource consumption. The ulipristal strategy dominated leuprolide as it provided patients with more quality-adjusted life years (0.177 versus 0.165) at a lower cost ($1,273 versus$1,366). Across a range of sensitivity analyses, the results remained robust except to the dose of the comparator drug. If leuprolide was administered at 11.25 mg, once every 3 months, the expected cost for the leuprolide strategy would decline and the associated incremental cost-utility ratio for ulipristal would be $168/quality-adjusted life year. Conclusion: Ulipristal offers a unique opportunity to effectively and rapidly control menstrual bleeding in patients with uterine fibroids; thereby improving their quality of life while minimizing the probability of moderate-to-severe hot flashes that are common with leuprolide. The current economic analysis suggests that ulipristal remains the dominant strategy across extensive sensitivity analyses. Keywords: cost-utility analysis, uterine leiomyomas, preoperative care, decision tree, menorrhagi