755 research outputs found

    Modelling the impact of prescribed global warming on runoff from headwater catchments of the Irrawaddy River and their implications for the water level regime of Loktak Lake, northeast India

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    Climate change is likely to have major implications for wetland ecosystems, which will include altered water level regimes due to modifications in local and catchment hydrology. However, substantial uncertainty exists in the precise impacts of climate change on wetlands due in part to uncertainty in GCM projections. This paper explores the impacts of climate change upon river discharge within three sub-catchments of Loktak Lake, an internationally important wetland in northeast India. This is achieved by running pattern-scaled GCM output through distributed hydrological models (developed using MIKE SHE) of each sub-catchment. The impacts of climate change upon water levels within Loktak Lake are subsequently investigated using a water balance model. Two groups of climate change scenarios are investigated. Group 1 uses results from seven different GCMs for an increase in global mean temperature of 2 A degrees C, the purported threshold of ''dangerous'' climate change, whilst Group 2 is based on results from the HadCM3 GCM for increases in global mean temperature between 1 A degrees C and 6 A degrees C. Results from the Group 1 scenarios show varying responses between the three sub-catchments. The majority of scenario-sub-catchment combinations (13 out of 21) indicate increases in discharge which vary from < 1% to 42% although, in some cases, discharge decreases by as much as 20%. Six of the GCMs suggest overall increases in river flow to Loktak Lake (2-27%) whilst the other results in a modest (6%) decline. In contrast, the Group 2 scenarios lead to an almost linear increase in total river flow to Loktak Lake with increasing temperature (up to 27% for 6 A degrees C), although two sub-catchments experience reductions in mean discharge for the smallest temperature increases. In all but one Group 1 scenario, and all the Group 2 scenarios, Loktak Lake water levels are higher, regularly reaching the top of a downstream hydropower barrage that impounds the lake and necessitating the release of water for barrage structural stability. Although elevated water levels may permit enhanced abstraction for irrigation and domestic uses, future increases in hydropower generation are limited by existing infrastructure. The higher water levels are likely to exacerbate existing ecological deterioration within the lake as well as enhancing problems of flooding of lakeside communities

    Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer

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    Introduction Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach. Methods Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, n = 84), gene expression profiling (n = 47), matched pre- and post-AI aCGH (n = 19 pairs) and Ki67-based AI-response analysis (n = 39). Results Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1). Conclusions These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response

    Lack of association between HLA antigen DR3 and α<inf>1</inf> deficiency in liver transplant recipients

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    The relationship between α1-antitrypsin deficiency (α-ATD) and the HLA antigen system was studied in 32 liver transplant recipients. Despite previous reports of an association of HLA antigen DR3 with homozygosity for α-AT ZZ, no such association was seen in this population of α-ATD homozygous ZZ patients with advanced hepatic disease. Thus, the reported association of HLA class II antigens and homozygosity for the Z allele for α-AT may be an artifact of either a small study population or geographic inbreeding and a coincidental association of certain HLA antigens with the presence of homozygosity for the Z allele of α-AT. © 1993 Plenum Publishing Corporation

    Investigating Executive Working Memory and Phonological Short-Term Memory in Relation to Fluency and Self-Repair Behavior in L2 Speech

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    This paper reports the findings of a study investigating the relationship of executive working memory (WM) and phonological short-term memory (PSTM) to fluency and self-repair behavior during an unrehearsed oral task performed by second language (L2) speakers of English at two levels of proficiency, elementary and lower intermediate. Correlational analyses revealed a negative relationship between executive WM and number of pauses in the lower intermediate L2 speakers. However, no reliable association was found in our sample between executive WM or PSTM and self-repair behavior in terms of either frequency or type of self-repair. Taken together, our findings suggest that while executive WM may enhance performance at the conceptualization and formulation stages of the speech production process, self-repair behavior in L2 speakers may depend on factors other than working memory

    Reciprocity and the tragedies of maintaining and providing the commons

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    Social cooperation often requires collectively beneficial but individually costly restraint to maintain a public good, or it needs costly generosity to create one. Status quo effects predict that maintaining a public good is easier than providing a new one. Here, we show experimentally and with simulations that even under identical incentives, low levels of cooperation (the ‘tragedy of the commons’) are systematically more likely in maintenance than provision. Across three series of experiments, we find that strong and weak positive reciprocity, known to be fundamental tendencies underpinning human cooperation, are substantially diminished under maintenance compared with provision. As we show in a fourth experiment, the opposite holds for negative reciprocity (‘punishment’). Our findings suggest that incentives to avoid the ‘tragedy of the commons’ need to contend with dilemma specific reciprocity

    External validation, update and development of prediction models for pre-eclampsia using an Individual Participant Data (IPD) meta-analysis: the International Prediction of Pregnancy Complication Network (IPPIC pre-eclampsia) protocol.

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    Background: Pre-eclampsia, a condition with raised blood pressure and proteinuria is associated with an increased risk of maternal and offspring mortality and morbidity. Early identification of mothers at risk is needed to target management. Methods/design: We aim to systematically review the existing literature to identify prediction models for pre-eclampsia. We have established the International Prediction of Pregnancy Complication Network (IPPIC), made up of 72 researchers from 21 countries who have carried out relevant primary studies or have access to existing registry databases, and collectively possess data from more than two million patients. We will use the individual participant data (IPD) from these studies to externally validate these existing prediction models and summarise model performance across studies using random-effects meta-analysis for any, late (after 34 weeks) and early (before 34 weeks) onset pre-eclampsia. If none of the models perform well, we will recalibrate (update), or develop and validate new prediction models using the IPD. We will assess the differential accuracy of the models in various settings and subgroups according to the risk status. We will also validate or develop prediction models based on clinical characteristics only; clinical and biochemical markers; clinical and ultrasound parameters; and clinical, biochemical and ultrasound tests. Discussion: Numerous systematic reviews with aggregate data meta-analysis have evaluated various risk factors separately or in combination for predicting pre-eclampsia, but these are affected by many limitations. Our large-scale collaborative IPD approach encourages consensus towards well developed, and validated prognostic models, rather than a number of competing non-validated ones. The large sample size from our IPD will also allow development and validation of multivariable prediction model for the relatively rare outcome of early onset pre-eclampsia. Trial registration: The project was registered on Prospero on the 27 November 2015 with ID: CRD42015029349

    Modelling the impact of prescribed global warming on runoff from headwater catchments of the Irrawaddy River and their implications for the water level regime of Loktak Lake, northeast India

    Get PDF
    Climate change is likely to have major implications for wetland ecosystems, which will include altered water level regimes due to modifications in local and catchment hydrology. However, substantial uncertainty exists in the precise impacts of climate change on wetlands due in part to uncertainty in GCM projections. This paper explores the impacts of climate change upon river discharge within three sub-catchments of Loktak Lake, an internationally important wetland in northeast India. This is achieved by running pattern-scaled GCM output through distributed hydrological models (developed using MIKE SHE) of each sub-catchment. The impacts of climate change upon water levels within Loktak Lake are subsequently investigated using a water balance model. Two groups of climate change scenarios are investigated. Group 1 uses results from seven different GCMs for an increase in global mean temperature of 2 A degrees C, the purported threshold of ''dangerous'' climate change, whilst Group 2 is based on results from the HadCM3 GCM for increases in global mean temperature between 1 A degrees C and 6 A degrees C. Results from the Group 1 scenarios show varying responses between the three sub-catchments. The majority of scenario-sub-catchment combinations (13 out of 21) indicate increases in discharge which vary from < 1% to 42% although, in some cases, discharge decreases by as much as 20%. Six of the GCMs suggest overall increases in river flow to Loktak Lake (2-27%) whilst the other results in a modest (6%) decline. In contrast, the Group 2 scenarios lead to an almost linear increase in total river flow to Loktak Lake with increasing temperature (up to 27% for 6 A degrees C), although two sub-catchments experience reductions in mean discharge for the smallest temperature increases. In all but one Group 1 scenario, and all the Group 2 scenarios, Loktak Lake water levels are higher, regularly reaching the top of a downstream hydropower barrage that impounds the lake and necessitating the release of water for barrage structural stability. Although elevated water levels may permit enhanced abstraction for irrigation and domestic uses, future increases in hydropower generation are limited by existing infrastructure. The higher water levels are likely to exacerbate existing ecological deterioration within the lake as well as enhancing problems of flooding of lakeside communities

    Functional MRI evidence for the decline of word retrieval and generation during normal aging

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    International audienceThis fMRI study aimed to explore the effect of normal aging on word retrieval and generation. The question addressed is whether lexical production decline is determined by a direct mechanism, which concerns the language operations or is rather indirectly induced by a decline of executive functions. Indeed, the main hypothesis was that normal aging does not induce loss of lexical knowledge, but there is only a general slowdown in retrieval mechanisms involved in lexical processing , due to possible decline of the executive functions. We used three tasks (verbal fluency, object naming , and semantic categorization). Two groups of participants were tested (Young, Y and Aged, A), without cognitive and psychiatric impairment and showing similar levels of vocabulary. Neuropsychological testing revealed that older participants had lower executive function scores, longer processing speeds, and tended to have lower verbal fluency scores. Additionally, older participants showed higher scores for verbal automa-tisms and overlearned information. In terms of behav-ioral data, older participants performed as accurate as younger adults, but they were significantly slower for the semantic categorization and were less fluent for verbal fluency task. Functional MRI analyses suggested that older adults did not simply activate fewer brain regions involved in word production, but they actually showed an atypical pattern of activation. Significant correlations between the BOLD (Blood Oxygen Level Dependent) signal of aging-related (A > Y) regions and cognitive scores suggested that this atypical pattern of the activation may reveal several compensatory mechanisms (a) to overcome the slowdown in retrieval, due to the decline of executive functions and processing speed and (b) to inhibit verbal automatic processes. The BOLD signal measured in some other aging-dependent regions did not correlate with the behavioral and neuro-psychological scores, and the overactivation of these uncorrelated regions would simply reveal dedifferentia-tion that occurs with aging. Altogether, our results suggest that normal aging is associated with a more difficult access to lexico-semantic operations and representations by a slowdown in executive functions, without any conceptual loss

    Brand Suicide? Memory and Liking of Negative Brand Names

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    Negative brand names are surprisingly common in the marketplace (e.g., Poison perfume; Hell pizza, and Monster energy drink), yet their effects on consumer behavior are currently unknown. Three studies investigated the effects of negative brand name valence on brand name memory and liking of a branded product. Study 1 demonstrates that relative to nonnegative brand names, negative brand names and their associated logos are better recognised. Studies 2 and 3 demonstrate that negative valence of a brand name tends to have a detrimental influence on product evaluation with evaluations worsening as negative valence increases. However, evaluation is also dependent on brand name arousal, with high arousal brand names resulting in more positive evaluations, such that moderately negative brand names are equally as attractive as some non-negative brand names. Study 3 shows evidence for affective habituation, whereby the effects of negative valence reduce with repeated exposures to some classes of negative brand name
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