Neuroscience-informed classification of prevention interventions in substance use disorders : an RDoC-based approach

Neuroscience has contributed to uncover the mechanisms underpinning substance use disorders (SUD). The next frontier is to leverage these mechanisms as active targets to create more effective interventions for SUD treatment and prevention. Recent large-scale cohort studies from early childhood are generating multiple levels of neuroscience-based information with the potential to inform the development and refinement of future preventive strategies. However, there are still no available well-recognized frameworks to guide the integration of these multi-level datasets into prevention interventions. The Research Domain Criteria (RDoC) provides a neuroscience-based multi-system framework that is well suited to facilitate translation of neurobiological mechanisms into behavioral domains amenable to preventative interventions. We propose a novel RDoC-based framework for prevention science and adapted the framework for the existing preventive interventions. From a systematic review of randomized controlled trials using a person-centered drug/alcohol preventive approach for adolescents, we identified 22 unique preventive interventions. By teasing apart these 22 interventions into the RDoC domains, we proposed distinct neurocognitive trajectories which have been recognized as precursors or risk factors for SUDs, to be targeted, engaged and modified for effective addiction prevention.Peer reviewe

Management Effects on Greenhouse Gas Dynamics in Fen Ditches

Globally, large areas of peatland have been drained through the digging of ditches, generally to increase agricultural production. By lowering the water table it is often assumed that drainage reduces landscape-scale emissions of methane (CH4) into the atmosphere to negligible levels. However, drainage ditches themselves are known to be sources of CH4 and other greenhouse gases (GHGs), but emissions data are scarce, particularly for carbon dioxide (CO2) and nitrous oxide (N2O), and show high spatial and temporal variability. Here, we report dissolved GHGs and diffusive fluxes of CH4 and CO2 from ditches at three UK lowland fens under different management; semi-natural fen, cropland, and cropland restored to low-intensity grassland. Ditches at all three fens emitted GHGs to the atmosphere, but both fluxes and dissolved GHGs showed extensive variation both seasonally and within-site. CH4 fluxes were particularly large, with medians peaking at all three sites in August at 120-230 mg m-2 d-1. Significant between site differences were detected between the cropland and the other two sites for CO2 flux and all three dissolved GHGs, suggested that intensive agriculture has major effects on ditch biogeochemistry. Multiple regression models using environmental and water chemistry data were able to explain 29-59% of observed variation in dissolved GHGs. Annual CH4 fluxes from the ditches were 37.8, 18.3 and 27.2 g CH4 m-2 yr-1 for the semi-natural, grassland and cropland, and annual CO2 fluxes were similar (1100 to 1440 g CO2 m-2 yr-1) among sites. We suggest that fen ditches are important contributors to landscape-scale GHG emissions, particularly for CH4. Ditch emissions should be included in GHG budgets of human modified fens, particularly where drainage has removed the original terrestrial CH4 source, e.g. agricultural peatlands

Cost-effectiveness of prophylactic cranial irradiation in stage III non-small cell lung cancer

INTRODUCTION In stage III non-small cell lung cancer (NSCLC), prophylactic cranial irradiation (PCI) reduces the brain metastases incidence and prolongs the progression-free survival without improving overall survival. PCI increases the risk of toxicity and is currently not adopted in routine care. Our objective was to assess the cost-effectiveness of PCI compared with no PCI in stage III NSCLC from a Dutch societal perspective. METHODS A cohort partitioned survival model was developed based on individual patient data from three randomized phase III trials (N = 670). Quality-adjusted life years (QALYs) and costs were estimated over a lifetime time horizon. A willingness-to-pay (WTP) threshold of €80,000 per QALY was adopted. Sensitivity and scenario analyses were performed to address parameter uncertainty and to explore what parameters had the greatest impact on the cost-effectiveness results. RESULTS PCI was more effective and costly (0.443 QALYs, €10,123) than no PCI, resulting in an incremental cost-effectiveness ratio (ICER) of €22,843 per QALY gained. The probability of PCI being cost-effective at a WTP threshold of €80,000 per QALY was 93%. The probability of PCI gaining three and six additional months of life were 76% and 56%. The scenario analysis adding durvalumab increased the ICER to €35,159 per QALY gained. Using alternative survival distributions had little impact on the ICER. Assuming fewer PCI fractions and excluding indirect costs decreased the ICER to €18,263 and €5554 per QALY gained. CONCLUSION PCI is cost-effective compared to no PCI in stage III NSCLC, and could therefore, from a cost-effectiveness perspective, be considered in routine care

Multidimensional family therapy decreases the rate of externalising behavioural disorder symptoms in cannabis abusing adolescents: Outcomes of the INCANT trial

Background: US-based trials have shown that Multidimensional Family Therapy (MDFT) not only reduces substance abuse among adolescents, but also decreases mental and behavioural disorder symptoms, most notably externalising symptoms. In the INCANT trial, MDFT decreased the rate of cannabis dependence among Western European youth. We now focus on other INCANT outcomes, i.e., lessening of co-morbidity symptoms and improvement of family functioning.Methods: INCANT was a randomised controlled trial comparing MDFT with individual therapy (IP) at and across sites in Berlin, Brussels, Geneva, The Hague, and Paris. We recruited 450 boys and girls aged 13 up to 18 years with a cannabis use disorder, and their parent(s), and followed them for 12 months. Mental and behavioural characteristics (classified as 'externalising' or 'internalising') and family conflict and cohesion were assessed.Results: From intake through 12 months, MDFT and IP groups improved on all outcome measures. Models including treatment, site, and referral source showed that MDFT outperformed IP in reducing externalising symptoms.Adolescents were either self-referred to treatment (mostly on the initiative from people close to the teen) or referred under some measure of coercion by an external authority. These two groups reacted equally well to treatment.Conclusions: Both MDFT and IP reduced the rate of externalising and internalising symptoms and improved family functioning among adolescents with a cannabis use disorder. MDFT outperformed IP in decreasing the rate of externalising symptoms. Contrary to common beliefs among therapists in parts of Western Europe, the 'coerced' adolescents did at least as well in treatment as the self-referred adolescents.MDFT shows promise as a treatment for both substance use disorders and externalising symptoms

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson

Measurement of the top quark pair cross section with ATLAS in pp collisions at √s=7 TeV using final states with an electron or a muon and a hadronically decaying τ lepton

A measurement of the cross section of top quark pair production in proton-proton collisions recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 7 TeV is reported. The data sample used corresponds to an integrated luminosity of 2.05 fb -1. Events with an isolated electron or muon and a τ lepton decaying hadronically are used. In addition, a large missing transverse momentum and two or more energetic jets are required. At least one of the jets must be identified as originating from a b quark. The measured cross section, σtt-=186±13(stat.)±20(syst.)±7(lumi.) pb, is in good agreement with the Standard Model prediction

Measurement of the top quark-pair production cross section with ATLAS in pp collisions at \sqrt{s}=7\TeV

A measurement of the production cross-section for top quark pairs(\ttbar) in $pp$ collisions at \sqrt{s}=7 \TeV is presented using data recorded with the ATLAS detector at the Large Hadron Collider. Events are selected in two different topologies: single lepton (electron $e$ or muon $\mu$) with large missing transverse energy and at least four jets, and dilepton ($ee$, $\mu\mu$ or $e\mu$) with large missing transverse energy and at least two jets. In a data sample of 2.9 pb-1, 37 candidate events are observed in the single-lepton topology and 9 events in the dilepton topology. The corresponding expected backgrounds from non-\ttbar Standard Model processes are estimated using data-driven methods and determined to be $12.2 \pm 3.9$ events and $2.5 \pm 0.6$ events, respectively. The kinematic properties of the selected events are consistent with SM \ttbar production. The inclusive top quark pair production cross-section is measured to be \sigmattbar=145 \pm 31 ^{+42}_{-27} pb where the first uncertainty is statistical and the second systematic. The measurement agrees with perturbative QCD calculations.Comment: 30 pages plus author list (50 pages total), 9 figures, 11 tables, CERN-PH number and final journal adde

Hunt for new phenomena using large jet multiplicities and missing transverse momentum with ATLAS in 4.7 fb−1 of √s=7 TeV proton-proton collisions

Results are presented of a search for new particles decaying to large numbers of jets in association with missing transverse momentum, using 4.7 fb−1 of pp collision data at s√=7TeV collected by the ATLAS experiment at the Large Hadron Collider in 2011. The event selection requires missing transverse momentum, no isolated electrons or muons, and from ≥6 to ≥9 jets. No evidence is found for physics beyond the Standard Model. The results are interpreted in the context of a MSUGRA/CMSSM supersymmetric model, where, for large universal scalar mass m 0, gluino masses smaller than 840 GeV are excluded at the 95% confidence level, extending previously published limits. Within a simplified model containing only a gluino octet and a neutralino, gluino masses smaller than 870 GeV are similarly excluded for neutralino masses below 100 GeV

Measurement of the inclusive isolated prompt photon cross-section in pp collisions at sqrt(s)= 7 TeV using 35 pb-1 of ATLAS data

A measurement of the differential cross-section for the inclusive production of isolated prompt photons in pp collisions at a center-of-mass energy sqrt(s) = 7 TeV is presented. The measurement covers the pseudorapidity ranges |eta|<1.37 and 1.52<=|eta|<2.37 in the transverse energy range 45<=E_T<400GeV. The results are based on an integrated luminosity of 35 pb-1, collected with the ATLAS detector at the LHC. The yields of the signal photons are measured using a data-driven technique, based on the observed distribution of the hadronic energy in a narrow cone around the photon candidate and the photon selection criteria. The results are compared with next-to-leading order perturbative QCD calculations and found to be in good agreement over four orders of magnitude in cross-section.Comment: 7 pages plus author list (18 pages total), 2 figures, 4 tables, final version published in Physics Letters