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Alternative Cause (alternative + cause)
Selected AbstractsSafety of nevirapine in pregnancyHIV MEDICINE, Issue 1 2007U Natarajan Background Nevirapine has been widely used in pregnancy for its efficacy, low pill burden, bioavailability and rapid transplacental transfer. Concern about nevirapine toxicity during pregnancy has emerged over recent years. Objectives The aims of the study were to document the frequency of cutaneous and hepatic toxicity secondary to nevirapine use during pregnancy and to compare rates in women starting nevirapine during the current pregnancy with those in women who had commenced nevirapine prior to the current pregnancy. Design This was a retrospective, comparative, five-centre study carried out in London, UK, in 1997,2003. Methods All HIV-1-infected women who received nevirapine as part of combination antiretroviral therapy (ART) during pregnancy were included in the study. Data on demographics, HIV infection risk, Centers for Disease Control and Prevention (CDC) status, surrogate markers at initiation of therapy, other medications hepatitis B and C virus coinfection and clinical data relating to potential toxicity were collated and analysed. Results Fifteen of 235 eligible women (6.4%) developed rash and eight (3.4%) developed hepatotoxicity, including four with coexistent rash, giving a combined incidence of 19 potential cases of nevirapine toxicity during pregnancy (8.1%). Alternative causes of rash/hepatotoxicity were suspected in seven cases and only 10 mothers (5.8%) discontinued nevirapine. Of the 170 women who commenced nevirapine during this pregnancy, 13 (7.6%) developed rash and eight (4.7%) hepatotoxicity, a combined incidence of 10%. Only two of 65 women with nevirapine exposure prior to this pregnancy developed rash (3.1%). Conclusions Nevirapine-containing ART was well tolerated in this cohort of pregnant women. Although pregnancy did not appear to increase the risk of nevirapine-associated toxicity compared to published adult data, CD4 count may be less predictive of toxicity in pregnancy. [source] Discounting and the role of the relation between causesEUROPEAN JOURNAL OF SOCIAL PSYCHOLOGY, Issue 2 2005Frank Van Overwalle This research investigates how the relation between two causes (i.e. whether they co-occur or not) affects the likelihood to discount one of them. In two experiments, two causes were either systematically paired together (positive relation), were paired with many other causes (independent relation), or were never paired together (negative relation). The results indicate that discounting of one of the causes (target cause) depends on the relation with the other cause (alternative cause) and the order in which the alternative cause was presented and produced the outcome alone. If information on the independent outcome of the alternative cause came prior to the joint outcome of the alternative and target cause (forward order), then discounting of the target cause occurred regardless of the relation between the two causes. If, however, information on the independent outcome of the alternative cause came after the joint outcome of the alternative and target cause (backward order), then discounting of the target cause occurred mainly when there was a positive or negative relation between the causes, but not when there was an independent relation. The degree of backward discounting given a positive or negative relation was largely identical. These results are consistent with the retrospective revaluation hypothesis of Dickinson and Burke (1996) and shed new light on the role of the relation between causes on discounting. Copyright © 2004 John Wiley & Sons, Ltd. [source] What is the basis of transmissible spongiform encephalopathy induced neurodegeneration and can it be repaired?NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 1 2002J. R. FraserArticle first published online: 8 APR 200 Once an animal becomes infected with a prion disease, or transmissible spongiform encephalopathy (TSE), the progression of infection is relentless and inevitably fatal, although often with such prolonged incubation periods that an alternative cause of death can intervene. Infection has been compared to ,setting a clock' which then runs inexorably as the disease spreads, usually through the lymphoreticular system and then via peripheral nerves to the central nervous system (CNS), although the mechanism controlling the protracted progression is not known. Clinical disease develops as characteristic degenerative changes in the CNS progress, but the molecular basis for this pathology is not clear, particularly the relationship between the deposition of abnormal PrP and neuronal dysfunction. Recent research has identified several means of slowing (if not stopping) the clock when infection has not yet reached the CNS; although the potential for later stage therapies seems limited, neuroprotective strategies which have been shown to be effective in other neurodegenerative conditions may also ameliorate TSE induced CNS pathology. This review focuses on our current knowledge of the key events following infection of the CNS and the opportunities for intervention once the CNS has become infected. [source] Nuclear ,-catenin in basal cell carcinoma correlates with increased proliferationBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2004G. Saldanha Summary Background Virtually all BCCs have deregulation of the Hedgehog (Hh) signalling pathway and a proportion show nuclear ,-catenin accumulation. The latter is thought to be due to Hh pathway-directed Wnt expression but this has not been tested. An alternative cause of nuclear ,-catenin accumulation is gene mutation, which stabilizes the protein. Theoretically, reduced E-cadherin expression could also be important because it can sequester ,-catenin at the cell membrane. In turn, nuclear ,-catenin can increase expression of MYC and cyclin D1, thus potentially altering proliferation. Objectives To assess whether nuclear ,-catenin occurs in BCC, and to look at potential causes and consequences. Methods Nuclear ,-catenin was assessed by immunohistochemistry, and its causes by analysis of E-cadherin expression, ,-catenin exon 3 mutation and WNT5A expression. Its consequences were assessed by analysing proliferation. Results We found nuclear ,-catenin in 20 of 86 paraffin-embedded sections of BCCs using immunohistochemistry. BCCs showed increased WNT5A relative to the surrounding skin. No mutations in exon 3 of the ,-catenin gene were found in 10 cases. There was no association between ,-catenin localization and E-cadherin expression. Tumours with nuclear ,-catenin had significantly higher proliferation (P < 0·01). Conclusions The absence of ,-catenin gene mutations indicate that the Hh pathway-directed Wnt signalling remains the most likely cause of nuclear ,-catenin accumulation in BCC. Additionally, the correlation with increased proliferation is the first evidence that nuclear ,-catenin may have a biological effect. However, a causal link between Hh pathway deregulation, Wnt ligand overexpression, nuclear ,-catenin accumulation and increased proliferation remains to be confirmed. [source] A Causal Model Theory of the Meaning of Cause, Enable, and PreventCOGNITIVE SCIENCE - A MULTIDISCIPLINARY JOURNAL, Issue 1 2009Steven Sloman Abstract The verbs cause, enable, and prevent express beliefs about the way the world works. We offer a theory of their meaning in terms of the structure of those beliefs expressed using qualitative properties of causal models, a graphical framework for representing causal structure. We propose that these verbs refer to a causal model relevant to a discourse and that "A causes B" expresses the belief that the causal model includes a link from A to B. "A enables/allows B" entails that the model includes a link from A to B, that A represents a category of events necessary for B, and that an alternative cause of B exists. "A prevents B" entails that the model includes a link from A to B and that A reduces the likelihood of B. This theory is able to account for the results of four experiments as well as a variety of existing data on human reasoning. [source] Assessment of drug-induced liver injury in clinical practiceFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2008Ma Isabel Lucena Abstract Currently, pharmaceutical preparations are serious contributors to liver disease, with hepatotoxicity ranking as the most frequent cause for acute liver failure and post-marketing regulatory decisions. The diagnostic approach of drug-induced liver injury (DILI) is still rudimentary and inaccurate because of the lack of reliable markers for use in general clinical practice. To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug's hepatotoxic potential, the exclusion of alternative causes of liver damage, and the ability to detect the presence of subtle data that favour a toxic aetiology. Clinical and laboratory data may also be assessed with algorithms or clinical scales, which may add consistency to the clinical judgment by translating the suspicion into a quantitative score. The CIOMS/RUCAM instrument is considered at present the best method for assessing causality in DILI, although it could be improved through the use of large database of bona fide DILI cases for validation criteria. [source] Two Varieties of Conditionals and Two Kinds of Defeaters Help Reveal Two Fundamental Types of ReasoningMIND & LANGUAGE, Issue 4 2006POLITZER GUY The distinction between disabling conditions and alternative causes is shown to be a special case of Pollock's (1987) distinction between ,rebutting' and ,undercutting' defeaters. ,Inferential' conditionals are shown to come in two varieties, one that is sensitive to rebutters, the other to undercutters. It is thus predicted and demonstrated in two experiments that the type of inferential conditional used as the major premise of conditional arguments can reverse the heretofore classic, distinctive effects of defeaters. [source] Conceptual bases for quantifying the role of the environment on gene evolution: the participation of positive selection and neutral evolutionBIOLOGICAL REVIEWS, Issue 4 2007Anthony Levasseur Abstract To demonstrate that a given change in the environment has contributed to the emergence of a given genotypic and phenotypic shift during the course of evolution, one should ask to what extent such shifts would have occurred without environmental change. Of course, such tests are rarely practical but phenotypic novelties can still be correlated to genomic shifts in response to environmental changes if enough information is available. We surveyed and re-evaluated the published data in order to estimate the role of environmental changes on the course of species and genomic evolution. Only a few published examples clearly demonstrate a causal link between a given environmental change and the fixation of a genomic variant resulting in functional modification (gain, loss or alteration of function). Many others suggested a link between a given phenotypic shift and a given environmental change but failed to identify the underlying genomic determinant(s) and/or the associated functional consequence(s). The proportion of genotypic and phenotypic variation that is fixed concomitantly with environmental changes is often considered adaptive and hence, the result of positive selection, even though alternative causes, such as genetic drift, are rarely investigated. Therefore, the second aim herein is to review evidence for the mechanisms leading to fixation. [source] | |||||||||||||