949 resultados para Funder, David C


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We investigate the use of an arrayed waveguide grating (AWG) to interrogate both fibre Bragg grating (FBG) and interferometric sensors. A broadband light source is used to illuminate both the FBG and interferometric sensors. Reflected spectral information is directed to an AWG with integral photodetectors providing 40 electrical outputs. To interrogate interferometric sensors we investigated the dual wavelength technique to measure the distance of a Fabry-Perot cavity, which produced a maximum unambiguous range of 1440μm with an active sensor. Three methods are described to interrogate FBG sensors. The first technique makes use of the reflected light intensity in an AWG channel passband from a narrow bandwidth grating, giving a usable range of 500με and a dynamic strain resolution of 96nε/√Hz at 30Hz. The second approach utilises wide gratings larger than the channel spacing of the AWG; by monitoring the intensity present in corresponding AWG channels an improved range of 1890με was achieved. The third method improves the dynamic range by utilising a heterodyne approach based on interferometric wavelength shift detection providing a dynamic strain resolution of 17nε/√Hz at 30Hz.

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The 5-HT7 receptor is linked with various CNS disorders. Using an automated solution phase synthesis a combinatorial library of 384 N-substituted N-[1-methyl-3-(4-methylpiperidin-1-yl)propyl]-arylsulfonamides was prepared with 24 chemically diverse amines 1-24 and 16 sulfonyl chlorides A-P. The chemical library of alkylated sulfonamides was evaluated in a receptor binding assay with [3]H-5-CT as ligand. The key synthetic step was the alkylation of a sulfonamide with iodide E, which was prepared from butanediol in 4 synthetic steps. The target compounds 1A, 1B .....24A ... 24P were purified by solvent extraction on a Teacan liquid handling system. Sulfonamide J20, B23, D23, G23, G23, J23 , I24 and O24 displayed a binding affinity IC50 between 100 nM and 10 nM. The crystalline J20 (IC50=39 nM) and O24 (IC50=83 nM) were evaluated further in the despair swimming test and the tail suspension assay. A significant antidepressant activity was found in mice of a greater magnitude than imipramine and fluoxetine at low doses. © 2006 Bentham Science Publishers Ltd.

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The purpose of this paper is to compare prices for a popular quick-service restaurant chain (i.e. McDonalds’) across countries throughout the world using the “Big Mac Index” published by “The Economist.” The index was originally developed to measure the valuation of international currencies against the U.S. dollar. The analysis in this study examines the relationship between the price of a Big Mac and other variables such as the cost of beef, price elasticity, and income. Finally, these relationships are reviewed to draw inferences concerning the use of demand, costs, and competition in setting prices.

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Involuntary episodic memories are memories that come into consciousness without preceding retrieval effort. These memories are commonplace and are relevant to multiple mental disorders. However, they are vastly understudied. We use a novel paradigm to elicit involuntary memories in the laboratory so that we can study their neural basis. In session one, an encoding session, sounds are presented with picture pairs or alone. In session two, in the scanner, sounds-picture pairs and unpaired sounds are reencoded. Immediately following, participants are split into two groups: a voluntary and an involuntary group. Both groups perform a sound localization task in which they hear the sounds and indicate the side from which they are coming. The voluntary group additionally tries to remember the pictures that were paired with the sounds. Looking at neural activity, we find a main effect of condition (paired vs. unpaired sounds) showing similar activity in both groups for voluntary and involuntary memories in regions typically associated with retrieval. There is also a main effect of group (voluntary vs. involuntary) in the dorsolateral prefrontal cortex, a region typically associated with cognitive control. Turning to connectivity similarities and differences between groups again, there is a main effect of condition showing paired > unpaired sounds are associated with a recollection network. In addition, three group differences were found: (1) increased connectivity between the pulvinar nucleus of the thalamus and the recollection network for the voluntary group, (2) a higher association between the voluntary group and a network that includes regions typically found in frontoparietal and cingulo-opercular networks, and (3) shorter path length for about half of the nodes in these networks for the voluntary group. Finally, we use the same paradigm to compare involuntary memories in people with posttraumatic stress disorder (PTSD) to trauma-controls. This study also included the addition of emotional pictures. There were two main findings. (1) A similar pattern of activity was found for paired > unpaired sounds for both groups but this activity was delayed in the PTSD group. (2) A similar pattern of activity was found for high > low emotion stimuli but it occurred early in the PTSD group compared to the control group. Our results suggest that involuntary and voluntary memories share the same neural representation but that voluntary memories are associated with additional cognitive control processes. They also suggest that disorders associated with cognitive deficits, like PTSD, can affect the processing of involuntary memories.

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The focus on how one is behaving, feeling, and thinking, provides a powerful source of self-knowledge. How is this self-knowledge utilized in the dynamic reconstruction of autobiographical memories? How, in turn, might autobiographical memories support identity and the self-system? I address these questions through a critical review of the literature on autobiographical memory and the self-system, with a special focus on the self-concept, self-knowledge, and identity. I then outline the methods and results of a prospective longitudinal study examining the effects of an identity change on memory for events related to that identity. Participant-rated memory characteristics, computer-generated ratings of narrative content and structure, and neutral-observer ratings of coherence were examined for changes over time related to an identity-change, as well as for their ability to predict an identity-change. The conclusions from this study are threefold: (1) when the rated centrality of an event decreases, the reported instances of retrieval, as well as the phenomenology associated with retrieval and the number of words used to describe the memory, also decrease; (2) memory accuracy (here, estimating past behaviors) was not influenced by an identity change; and (3) remembering is not unidirectional – characteristics of identity-relevant memories and the life story predict and may help support persistence with an identity (here, an academic trajectory).

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Assessing the habitability of deep-sea sediments undergoing compaction, compression, and subduction at convergent margins adds to our understanding of the limits of the terrestrial biosphere. In this work, we report exploratory biomarker data on sediments obtained at Ocean Drilling Program (ODP) Sites 1253, 1254, and 1255 during drilling at the Costa Rica subduction trench and forearc sedimentary wedge. The samples selected for postcruise biomarker analyses were located within intervals of potentially enhanced fluid flow within the décollement and sedimentary wedge fault zones (Sites 1254 and 1255) and within basal carbonates at the reference site (Site 1253). The passage of fluids that are geochemically distinct from ambient interstitial water provides a disequilibrium setting that may enhance habitability. Biomarker data show low levels of microbial biomass in subseafloor sediments sampled at the Costa Rica convergent margin as deep as ~370 meters below seafloor.

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In the past few years, it has become increasingly apparent that perchlorate (ClO4-) is present on all continents, except the polar regions where it had not yet been assessed, and that it may have a significant natural source. Here, we report on the discovery of perchlorate in soil and ice from several Antarctic Dry Valleys (ADVs) where concentrations reach up to 1100/µg/kg. In the driest ADV, perchlorate correlates with atmospherically deposited nitrate. Far from anthropogenic activity, ADV perchlorate provides unambiguous evidence that natural perchlorate is ubiquitous on Earth. The discovery has significant implications for the origin of perchlorate, its global biogeochemical interactions, and possible interactions with the polar ice sheets. The results support the hypotheses that perchlorate is produced globally and continuously in the Earth's atmosphere, that it typically accumulates in hyperarid areas, and that it does not build up in oceans or other wet environments most likely because of microbial reduction on a global scale.

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Piston cores from the continental margin off Nova Scotia show up to four discrete intervals of "brick-red sandy mud", which are up to 20 cm thick. The ages of these intervals are bracketed by several radiocarbon dates, and three fall in the range 12.5-14.1 ka (radiocarbon years with -0.4 kyr reservoir correction). The youngest dates from ~10.4 ka, placing it within the Younger Dryas. The distribution of the beds and their petrographic character indicate a source in the Gulf of Saint Lawrence. The grain size of these beds suggests that they comprise a coarse component transported by ice rafting that diminishes distally and a fine component that represents suspension fallout from a surface plume and resulting nepheloid layers. Graded brick-red beds in some cores were probably redeposited from turbidity currents. The lowermost bed on the Laurentian Fan and East Scotian Rise is immediately overlain by a carbonate-rich interval that can be identified all around the margin of the Grand Banks. This interval is correlated with detrital carbonate bed DC-1 in the Labrador Sea and Heinrich event H1 in the North Atlantic. The sequential occurrence of the two beds suggests that they may be a response to the same trigger, probably sea level rise, but that the Gulf of Saint Lawrence source was more easily destabilized.

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Northeast Pacific benthic foraminiferal d18O and d13 reveal repeated millennial-scale events of strong deep-sea ventilation (associated with nutrient depletion and/or high gas exchange) during stadial (cool, high ice volume) episodes from 10 to 60 ka, opposite the pattern in the deep North Atlantic. Two climate mechanisms may explain this pattern. North Pacific surface waters, chilled by atmospheric transmission from a cold North Atlantic and made saltier by reduced freshwater vapor transports, could have ventilated the deep Pacific from above. Alternatively, faster turnover of Pacific bottom and mid-depth waters, driven by Southern Ocean winds, may have compensated for suppressed North Atlantic Deep Water production during stadial intervals. During the Younger Dryas event (~11.6-13.0 cal ka), ventilation of the deep NE Pacific (~2700 m) lagged that in the Santa Barbara Basin (~450 m) by >500 years, suggesting that the NE Pacific was first ventilated at intermediate depth from above and then at greater depth from below. This apparent lag may reflect the adjustment time of global thermohaline circulation.

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International migration sets in motion a range of significant transnational processes that connect countries and people. How migration interacts with development and how policies might promote and enhance such interactions have, since the turn of the millennium, gained attention on the international agenda. The recognition that transnational practices connect migrants and their families across sending and receiving societies forms part of this debate. The ways in which policy debate employs and understands transnational family ties nevertheless remain underexplored. This article sets out to discern the understandings of the family in two (often intermingled) debates concerned with transnational interactions: The largely state and policydriven discourse on the potential benefits of migration on economic development, and the largely academic transnational family literature focusing on issues of care and the micro-politics of gender and generation. Emphasizing the relation between diverse migration-development dynamics and specific family positions, we ask whether an analytical point of departure in respective transnational motherhood, fatherhood or childhood is linked to emphasizing certain outcomes. We conclude by sketching important strands of inclusions and exclusions of family matters in policy discourse and suggest ways to better integrate a transnational family perspective in global migration-development policy.

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Online gambling is a popular activity among adolescents. However, there has been a notable increase in the number of young people who suffer or are on the verge of pathological gambling. We review the impact of online gambling on young people and discuss the desiderability of the concept of “gambling responsibly” in order to alert of their risks and effectively prevent access to minors. The main factors associated with pathological gambling are the age of start, the family environment, the infl uence of advertising, the consumption of stimulants, and the attitudes of the peer group. Both the government and the gaming industry itself should consider these factors and develop comprehensive plans that ensure a safe and controlled model game. In this context, advertising must take into account criteria of consumer protection knowing that even if they are not allowed, children can easily have access to online gambling. All agents involved, including public and social agents, must provide mechanisms for prevention and awareness of a problem that arouses little social consciousness and excessive carelessness.

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BACKGROUND:
Palliative care focuses on supporting patients diagnosed with advanced, incurable disease; it is 'family centered', with the patient and their family (the unit of care) being core to all its endeavours. However, approximately 30-50% of carers experience psychological distress which is typically under recognised and consequently not addressed. Family meetings (FM) are recommended as a means whereby health professionals, together with family carers and patients discuss psychosocial issues and plan care; however there is minimal empirical research to determine the net effect of these meetings and the resources required to implement them systematically. The aims of this study were to evaluate: (1) if family carers of hospitalised patients with advanced disease (referred to a specialist palliative care in-patient setting or palliative care consultancy service) who receive a FM report significantly lower psychological distress (primary outcome), fewer unmet needs, increased quality of life and feel more prepared for the caregiving role; (2) if patients who receive the FM experience appropriate quality of end-of-life care, as demonstrated by fewer hospital admissions, fewer emergency department presentations, fewer intensive care unit hours, less chemotherapy treatment (in last 30 days of life), and higher likelihood of death in the place of their choice and access to supportive care services; (3) the optimal time point to deliver FM and; (4) to determine the cost-benefit and resource implications of implementing FM meetings into routine practice.
METHODS:
Cluster type trial design with two way randomization for aims 1-3 and health economic modeling and qualitative interviews with health for professionals for aim 4.
DISCUSSION:
The research will determine whether FMs have positive practical and psychological impacts on the family, impacts on health service usage, and financial benefits to the health care sector. This study will also provide clear guidance on appropriate timing in the disease/care trajectory to provide a family meeting.

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BACKGROUND & AIMS: Gluteofemoral obesity (determined by measurement of subcutaneous fat in hip and thigh regions) could reduce risks of cardiovascular and diabetic disorders associated with abdominal obesity. We evaluated whether gluteofemoral obesity also reduces risk of Barrett's esophagus (BE), a premalignant lesion associated with abdominal obesity.

METHODS: We collected data from non-Hispanic white participants in 8 studies in the Barrett's and Esophageal Adenocarcinoma Consortium. We compared measures of hip circumference (as a proxy for gluteofemoral obesity) from cases of BE (n=1559) separately with 2 control groups: 2557 population-based controls and 2064 individuals with gastroesophageal reflux disease (GERD controls). Study-specific odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using individual participant data and multivariable logistic regression and combined using random effects meta-analysis.

RESULTS: We found an inverse relationship between hip circumference and BE (OR per 5 cm increase, 0.88; 95% CI, 0.81-0.96), compared with population-based controls in a multivariable model that included waist circumference. This association was not observed in models that did not include waist circumference. Similar results were observed in analyses stratified by frequency of GERD symptoms. The inverse association with hip circumference was only statistically significant among men (vs population-based controls: OR, 0.85; 95% CI, 0.76-0.96 for men; OR, 0.93; 95% CI, 0.74-1.16 for women). For men, within each category of waist circumference, a larger hip circumference was associated with decreased risk of BE. Increasing waist circumference was associated with increased risk of BE in the mutually adjusted population-based and GERD control models.

CONCLUSIONS: Although abdominal obesity is associated with increased risk of BE, there is an inverse association between gluteofemoral obesity and BE, particularly among men.

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Background: Esophageal adenocarcinoma (EA) is one of the fastest rising cancers in western countries. Barrett’s Esophagus (BE) is the premalignant precursor of EA. However, only a subset of BE patients develop EA, which complicates the clinical management in the absence of valid predictors. Genetic risk factors for BE and EA are incompletely understood. This study aimed to identify novel genetic risk factors for BE and EA.Methods: Within an international consortium of groups involved in the genetics of BE/EA, we performed the first meta-analysis of all genome-wide association studies (GWAS) available, involving 6,167 BE patients, 4,112 EA patients, and 17,159 representative controls, all of European ancestry, genotyped on Illumina high-density SNP-arrays, collected from four separate studies within North America, Europe, and Australia. Meta-analysis was conducted using the fixed-effects inverse variance-weighting approach. We used the standard genome-wide significant threshold of 5×10-8 for this study. We also conducted an association analysis following reweighting of loci using an approach that investigates annotation enrichment among the genome-wide significant loci. The entire GWAS-data set was also analyzed using bioinformatics approaches including functional annotation databases as well as gene-based and pathway-based methods in order to identify pathophysiologically relevant cellular pathways.Findings: We identified eight new associated risk loci for BE and EA, within or near the CFTR (rs17451754, P=4·8×10-10), MSRA (rs17749155, P=5·2×10-10), BLK (rs10108511, P=2·1×10-9), KHDRBS2 (rs62423175, P=3·0×10-9), TPPP/CEP72 (rs9918259, P=3·2×10-9), TMOD1 (rs7852462, P=1·5×10-8), SATB2 (rs139606545, P=2·0×10-8), and HTR3C/ABCC5 genes (rs9823696, P=1·6×10-8). A further novel risk locus at LPA (rs12207195, posteriori probability=0·925) was identified after re-weighting using significantly enriched annotations. This study thereby doubled the number of known risk loci. The strongest disease pathways identified (P<10-6) belong to muscle cell differentiation and to mesenchyme development/differentiation, which fit with current pathophysiological BE/EA concepts. To our knowledge, this study identified for the first time an EA-specific association (rs9823696, P=1·6×10-8) near HTR3C/ABCC5 which is independent of BE development (P=0·45).Interpretation: The identified disease loci and pathways reveal new insights into the etiology of BE and EA. Furthermore, the EA-specific association at HTR3C/ABCC5 may constitute a novel genetic marker for the prediction of transition from BE to EA. Mutations in CFTR, one of the new risk loci identified in this study, cause cystic fibrosis (CF), the most common recessive disorder in Europeans. Gastroesophageal reflux (GER) belongs to the phenotypic CF-spectrum and represents the main risk factor for BE/EA. Thus, the CFTR locus may trigger a common GER-mediated pathophysiology.