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Multiple Reasons (multiple + reason)
Selected AbstractsExposure and effects assessment of resident mink (Mustela vison) exposed to polychlorinated dibenzofurans and other dioxin-like compounds in the Tittabawassee River basin, Midland, Michigan, USA,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 10 2008Matthew J. Zwiernik Abstract Historically, sediments and floodplain soils of the Tittabawassee River (TR; MI, USA) have been contaminated with polychlorinated dibenzofurans (PCDFs), polychlorinated dibenzo- p -dioxins (PCDDs), and polychlorinatedbiphenyls (PCBs). Median concentrations of 2,3,7,8-tetrachlorodibenzo- p -dioxin equivalents (TEQs) based on 2006 World Health Organization tetrachloro-dibenzo- p -dioxin toxic equivalency factors (TEFs) in the diet of mink (Mustela vison) ranged from 6.8 × 10,1 ng TEQ/kg wet weight upstream of the primary source of PCDF to 3.1 × 101 ng TEQ/kg wet weight downstream. Estimates of toxicity reference values (TRVs) derived from laboratory studies with individual PCDDs/PCDFs and PCB congeners or mixtures of those congeners, as well as application of TEFs, were compared to site-specific measures of mink exposure. Hazard quotients based on exposures expressed as concentrations of TEQs in the 95th percentile of the mink diet or liver and the no-observable-adverse-effect TRVs were determined to be 1.7 and 8.6, respectively. The resident mink survey, however, including number of mink present, morphological measures, sex ratios, population age structure, and gross and histological tissue examination, indicated no observable adverse effects. This resulted for multiple reasons: First, the exposure estimate was conservative, and second, the predominantly PCDF congener mixture present in the TR appeared to be less potent than predicted from TEQs based on dose,response comparisons. Given this, there appears to be great uncertainty in comparing the measured concentrations of TEQs at this site to TRVs derived from different congeners or congener mixtures. Based on the lack of negative outcomes for any measurement endpoints examined, including jaw lesions, a sentinel indicator of possible adverse effects, and direct measures of effects on individual mink and their population, it was concluded that current concentrations of PCDDs/PCDFs were not causing adverse effects on resident mink of the TR. [source] Trainee perceptions of factors that influence learning transferINTERNATIONAL JOURNAL OF TRAINING AND DEVELOPMENT, Issue 1 2002Doo H. Lim The focus of the study was to assess learning transfer made by HRD professionals from a Korean organization for a training program on performance improvement technologies. Results revealed multiple reasons for high or low transfer and provide insights into the design of highly transferable training programs. [source] Price development in important anesthesia and critical care medicine journals in comparison to journals of other disciplinesACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2001J. Boldt Background: In today's climate of financial restrictions, libraries and individual subscribers complain about the price increase of scientific journals. The development in prices of anesthesia/critical care journals was analysed over the past 6 years and compared to prices of some journals of other disciplines. Methods: Important journals in the categories Anesthesiology, Emergency Medicine & Critical Care, Surgery, Medicine (General), and Cardiac & Cardiovascular Systems listed in the 1999 Science Citation Index of Journal Citation Report were included and prices for the years 1995 to 2000 were analysed. Results: Increase in prices ranged from +13% to +199%. The mean increase in journal prices was lowest in the category Anesthesiology (+61%), higher in the category Critical Care (+73%), and highest in the category Medicine, General (+101%). Changes in the impact factor (IF) varied widely, ranging from a decrease (Lancet: ,43%; J Neurosurg Anesth: ,44%) to a tremendous increase (e.g. Reg Anesth +165%; Ann Emerg Med +149%). The journals' size (number of articles or pages) did not increase proportionally with the increase in prices. Conclusion: A disproportionate rise in journal prices was seen over the past 6 years. The large increase in cost may have multiple reasons. The rapidly increasing cost of research journals may affect research quality because economic pressure may result in reduction in availibility of information due to cancellation of subscriptions to journals. [source] Back to Nukunuku: Employment, identity and return migration in TongaASIA PACIFIC VIEWPOINT, Issue 2 2008Nicole Maron Abstract: Return migration has escaped significant analysis in the Pacific island region. Both migration from and return migration to the Tongan village of Nukunuku are for multiple reasons, with migration centred on employment and education, and return centred on the social context of home and duty. Return is limited, with intentions not being matched with practice, and the village and national population not growing. However, return migrants acquire skills, capital and experience overseas, which can be transferred into a Tongan cultural context, although identities have changed during migration. Return migrants typically take up employment or acquire businesses on return, gain some social status from the outcome, and are neither failures nor retirees. Nonetheless, return engenders expectations and tensions exist between returnees and more established residents, although ultimately, return migrants contribute to household, local and national development, as part of an unfinished process. [source] Guardian Availability in Children Evaluated in the Emergency Department for Blunt Head TraumaACADEMIC EMERGENCY MEDICINE, Issue 1 2009James F. Holmes MD Abstract Background:, Enrolling children in research studies in the emergency department (ED) is typically dependent on the presence of a guardian to provide written informed consent. Objectives:, The objectives were to determine the rate of guardian availability during the initial ED evaluation of children with nontrivial blunt head trauma, to identify the reasons why a guardian is unavailable, and to compare clinical factors in patients with and without a guardian present during initial ED evaluation. Methods:, This was a prospective study of children (<18 years of age) presenting to a single Level 1 trauma center after nontrivial blunt head trauma over a 10-month period. Physicians documented patient history and physical examination findings onto a structured data form after initial evaluation. The data form contained data points regarding the presence or absence of the patient's guardian during the initial ED evaluation. For those children for whom the guardian was not available during the initial ED evaluation, the physicians completing the data forms documented the reasons for the absence. Results:, The authors enrolled 602 patients, of whom 271 (45%, 95% confidence interval [CI] = 41% to 49%) did not have a guardian available during the initial ED evaluation. In these 271 patients, 261 had reasons documented for lack of guardian availability, 43 of whom had multiple reasons. The most common of these was that the guardian did not ride in the ambulance (51%). Those patients without a guardian available were more likely to be older (mean age, 11.4 years vs. 7.6 years; p < 0.001), be victims of a motor vehicle collision (MVC; 130/268 [49%] vs. 35/328 [11%]; p < 0.001), have a Glasgow Coma Scale (GCS) score <14 (21/269 [7.8%] vs. 11/331 [3.3%]; p = 0.02), and undergo cranial computed tomography (CT) scanning (224/271 [83%] vs. 213/331 [64%]; p < 0.001). Multivariate analysis identified similar independent risk factors for lack of guardian presence. Conclusions:, Nearly one-half of children with nontrivial blunt head trauma evaluated in the ED may not have a guardian available during their initial ED evaluation. Patients whose guardians are not available at the time of initial ED evaluation are older and have more severe mechanisms of injury and more serious head trauma. ED research studies of pediatric trauma patients that require written informed consent from a guardian at the time of initial ED evaluation and treatment may have difficulty enrolling targeted sample size numbers and will likely be limited by enrollment bias. [source] Addressing Central Nervous System (CNS) Penetration in Drug Discovery: Basics and Implications of the Evolving New ConceptCHEMISTRY & BIODIVERSITY, Issue 11 2009Andreas Reichel Abstract Despite enormous efforts, achieving a safe and efficacious concentration profile in the brain remains one of the big challenges in central nervous system (CNS) drug discovery and development. Although there are multiple reasons, many failures are due to underestimating the complexity of the brain, also in terms of pharmacokinetics (PK). To this day, PK support of CNS drug discovery heavily relies on improving the blood,brain barrier (BBB) permeability in vitro and/or the brain/plasma ratio (Kp) in vivo, even though neither parameter can be reliably linked to pharmacodynamic (PD) and efficacy readouts. While increasing BBB permeability may shorten the onset of drug action, an increase in the total amount in brain may not necessarily increase the relevant drug concentration at the pharmacological target. Since the traditional Kp ratio is based on a crude homogenization of brain tissue, it ignores the compartmentalization of the brain and an increase favors non-specific binding to brain lipids rather than free drug levels. To better link exposure/PK to efficacy/PD and to delineate key parameters, an integrated approach to CNS drug discovery is emerging which distinguishes total from unbound brain concentrations. As the complex nature of the brain requires different compartments to be considered when trying to understand and improve new compounds, several complementary parameters need to be measured in vitro and in vivo, and integrated into a coherent model of brain penetration and distribution. The new paradigm thus concentrates on finding drug candidates with the right balance between free fraction in plasma and brain, and between rate and extent of CNS penetration. Integrating this data into a coherent model of CNS distribution which can be linked to efficacy will allow it to design compounds with an optimal mix in physicochemical, pharmacologic, and pharmacokinetic properties, ultimately mitigating the risk for failures in the clinic. [source] | ||||||||||