4,631 research outputs found

    Neural substrates of cue reactivity and craving in Gambling Disorder

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    Cue reactivity is an established procedure in addictions research for examining the subjective experience and neural basis of craving. This experiment sought to quantify cue-related brain responses in Gambling Disorder using personally tailored cues in conjunction with subjective craving, as well as a comparison with appetitive non-gambling stimuli. Participants with Gambling Disorder (n=19) attending treatment and 19 controls viewed personally tailored blocks of gambling-related cues, as well as neutral cues and highly appetitive (food) images during a functional MRI scan performed ~2-3 hours after a usual meal. fMRI analysis examined cue-related brain activity, cue-related changes in connectivity, and associations with block-by-block craving ratings. Craving ratings in the participants with Gambling Disorder increased following gambling cues compared with non-gambling cues. fMRI analysis revealed group differences in left insula and anterior cingulate cortex, with the Gambling Disorder group showing greater reactivity to the gambling cues, but no differences to the food cues. In participants with Gambling Disorder, craving to gamble correlated positively with gambling cue-related activity in the bilateral insula and ventral striatum, and negatively with functional connectivity between the ventral striatum and the medial PFC. Gambling cues, but not food cues, elicit increased brain responses in reward-related circuitry in individuals with Gambling Disorder (compared to controls), providing support for the incentive sensitisation theory of addiction. Activity in the insula co-varied with craving intensity, and may be a target for interventions.This study was funded by the Medical Research Council—MRC G1002226 (Nutt) and G1100554 (Clark). We wish to thank the study participants and the clinical team at Imanova, Centre for Imaging Sciences. The research was supported by the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre. SPS was funded by the Cambridge Home Scholarship Scheme (CHSS)

    Children, parents and pets exercising together (CPET) : exploratory randomised controlled trial

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    Levels of physical activity (PA) in UK children are much lower than recommended and novel approaches to its promotion are needed. The Children, Parents and Pets Exercising Together (CPET) study is the first exploratory randomised controlled trial (RCT) to develop and evaluate an intervention aimed at dog-based PA promotion in families. CPET aimed to assess the feasibility, acceptability and potential efficacy of a theory-driven, family-based, dog walking intervention for 9-11 year olds

    Initiation of V(D)J Recombination by Dβ-Associated Recombination Signal Sequences: A Critical Control Point in TCRβ Gene Assembly

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    T cell receptor (TCR) β gene assembly by V(D)J recombination proceeds via successive Dβ-to-Jβ and Vβ-to-DJβ rearrangements. This two-step process is enforced by a constraint, termed beyond (B)12/23, which prohibits direct Vβ-to-Jβ rearrangements. However the B12/23 restriction does not explain the order of TCRβ assembly for which the regulation remains an unresolved issue. The initiation of V(D)J recombination consists of the introduction of single-strand DNA nicks at recombination signal sequences (RSSs) containing a 12 base-pairs spacer. An RSS containing a 23 base-pairs spacer is then captured to form a 12/23 RSSs synapse leading to coupled DNA cleavage. Herein, we probed RSS nicks at the TCRβ locus and found that nicks were only detectable at Dβ-associated RSSs. This pattern implies that Dβ 12RSS and, unexpectedly, Dβ 23RSS initiate V(D)J recombination and capture their respective Vβ or Jβ RSS partner. Using both in vitro and in vivo assays, we further demonstrate that the Dβ1 23RSS impedes cleavage at the adjacent Dβ1 12RSS and consequently Vβ-to-Dβ1 rearrangement first requires the Dβ1 23RSS excision. Altogether, our results provide the molecular explanation to the B12/23 constraint and also uncover a ‘Dβ1 23RSS-mediated’ restriction operating beyond chromatin accessibility, which directs Dβ1 ordered rearrangements

    Variations in the Difference between Mean Sea Level measured either side of Cape Hatteras and Their Relation to the North Atlantic Oscillation

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    We consider the extent to which the difference in mean sea level (MSL) measured on the North American Atlantic coast either side of Cape Hatteras varies as a consequence of dynamical changes in the ocean caused by fluctuations in the North Atlantic Oscillation (NAO). From analysis of tide gauge data, we know that changes in MSL-difference and NAO index are correlated on decadal to century timescales enabling a scale factor of MSL-difference change per unit change in NAO index to be estimated. Changes in trend in the NAO index have been small during the past few centuries (when measured using windows of order 60–120 years). Therefore, if the same scale factor applies through this period of time, the corresponding changes in trend in MSL-difference for the past few centuries should also have been small. It is suggested thereby that the sea level records for recent centuries obtained from salt marshes (adjusted for long-term vertical land movements) should have essentially the same NAO-driven trends south and north of Cape Hatteras, only differing due to contributions from other processes such as changes in the Meridional Overturning Circulation or ‘geophysical fingerprints’. The salt marsh data evidently support this interpretation within their uncertainties for the past few centuries, and perhaps even for the past millennium. Recommendations are made on how greater insight might be obtained by acquiring more measurements and by improved modelling of the sea level response to wind along the shelf

    Regenerative medicine: from the laboratory looking out

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    Regenerative medicine has a rich and pluralistic history, characterised by a patchwork of innovation and blind alleys. As scientific researchers, our understanding of this hybrid field of regeneration in a historical and cultural context is far from complete, in part due to the range of non-medical contributory disciplines and a fascination with the future directions of research. This paper explores the different definitions of regenerative medicine and highlights issues faced in regenerative medicine research. We argue that a closer relationship between regenerative medicine and the humanities would enable researchers to better understand the historical context, ethical implications and public perception of this rapidly developing field. In many cases, this would be through better awareness of the existing expertise available in humanities research, which is often not visible to those in the laboratory

    The trophic importance of epiphytic algae in a freshwater macrophyte system (Potamogeton perfoliatus L.): stable isotope and fatty acid analyses

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    Stable isotope and fatty acid analyses were used to study carbon sources for animals in a submerged plant bed. Epiphytes growing on Potamogeton perfoliatus, sand microflora, and alder leaves were the most important carbon sources. The most abundant macrophyte, P. perfoliatus was unimportant as a food source. Modelling (IsoSource) showed that epiphytes were the most important food source for the most abundant benthic invertebrates, the isopod Asellus aquaticus (annual mean contribution 64%), the amphipod Gammarus pulex (66%), and the gastropod Potamopyrgus antipodarum (83%). The mean annual contributions of sand microflora were, respectively, 21, 19, and 9%; and of alder leaves, 15, 15, and 8% for these three species. The relative importance of carbon sources varied seasonally. The relative contribution of epiphytes was lowest for all three grazer species in July: A. aquaticus 38%, G. pulex 43%, and P. antipodarum 42%. A decline in epiphyte biomass in summer may have caused this switch to less attractive food sources. P. perfoliatus provided habitat and shelter for consumers, but food was mainly supplied indirectly by providing space for attached epiphytes, which are fast-growing and provide a highly nutritious food source

    The Falkland Islands’ palaeoecological response to millennial‐scale climate perturbations during the Pleistocene–Holocene transition: implications for future vegetation stability in the southern ocean islands

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    Oceanic island flora is vulnerable to future climate warming, which is likely to promote changes in vegetation composition, and invasion of non‐native species. Sub‐Antarctic islands are predicted to experience rapid warming during the next century; therefore, establishing trajectories of change in vegetation communities is essential for developing conservation strategies to preserve biological diversity. We present a Late‐glacial‐early Holocene (16 500–6450 cal a bp) palaeoecological record from Hooker's Point, Falkland Islands (Islas Malvinas), South Atlantic. This period spans the Pleistocene‐Holocene transition, providing insight into biological responses to abrupt climate change. Pollen and plant macrofossil records appear insensitive to climatic cooling during the Late‐glacial, but undergo rapid turnover in response to regional warming. The absence of trees throughout the Late‐glacial‐early Holocene enables the recognition of far‐travelled pollen from southern South America. The first occurrence of Nothofagus (southern beech) may reflect changes in the strength and/or position of the Southern Westerly Wind Belt during the Late‐glacial period. Peat inception and accumulation at Hooker's Point is likely to be promoted by the recalcitrant litter of wind‐adapted flora. This recalcitrant litter helps to explain widespread peatland development in a comparatively dry environment, and suggests that wind‐adapted peatlands can remain carbon sinks even under low precipitation regimes

    Azimuthal anisotropy and correlations at large transverse momenta in p+pp+p and Au+Au collisions at sNN\sqrt{s_{_{NN}}}= 200 GeV

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    Results on high transverse momentum charged particle emission with respect to the reaction plane are presented for Au+Au collisions at sNN\sqrt{s_{_{NN}}}= 200 GeV. Two- and four-particle correlations results are presented as well as a comparison of azimuthal correlations in Au+Au collisions to those in p+pp+p at the same energy. Elliptic anisotropy, v2v_2, is found to reach its maximum at pt3p_t \sim 3 GeV/c, then decrease slowly and remain significant up to pt7p_t\approx 7 -- 10 GeV/c. Stronger suppression is found in the back-to-back high-ptp_t particle correlations for particles emitted out-of-plane compared to those emitted in-plane. The centrality dependence of v2v_2 at intermediate ptp_t is compared to simple models based on jet quenching.Comment: 4 figures. Published version as PRL 93, 252301 (2004

    Studying the Underlying Event in Drell-Yan and High Transverse Momentum Jet Production at the Tevatron

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    We study the underlying event in proton-antiproton collisions by examining the behavior of charged particles (transverse momentum pT > 0.5 GeV/c, pseudorapidity |\eta| < 1) produced in association with large transverse momentum jets (~2.2 fb-1) or with Drell-Yan lepton-pairs (~2.7 fb-1) in the Z-boson mass region (70 < M(pair) < 110 GeV/c2) as measured by CDF at 1.96 TeV center-of-mass energy. We use the direction of the lepton-pair (in Drell-Yan production) or the leading jet (in high-pT jet production) in each event to define three regions of \eta-\phi space; toward, away, and transverse, where \phi is the azimuthal scattering angle. For Drell-Yan production (excluding the leptons) both the toward and transverse regions are very sensitive to the underlying event. In high-pT jet production the transverse region is very sensitive to the underlying event and is separated into a MAX and MIN transverse region, which helps separate the hard component (initial and final-state radiation) from the beam-beam remnant and multiple parton interaction components of the scattering. The data are corrected to the particle level to remove detector effects and are then compared with several QCD Monte-Carlo models. The goal of this analysis is to provide data that can be used to test and improve the QCD Monte-Carlo models of the underlying event that are used to simulate hadron-hadron collisions.Comment: Submitted to Phys.Rev.
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