Differential impact of two risk communications on antipsychotic prescribing to people with dementia in Scotland: segmented regression time series analysis 2001-2011

The two risk communications were associated with reductions in antipsychotic use, in ways which were compatible with marked differences in their content and dissemination. Further research is needed to ensure that the content and dissemination of regulatory risk communications is optimal, and to track their impact on intended and unintended outcomes. Although rates are falling, antipsychotic prescribing in dementia in Scotland remains unacceptably hig

Low Dopamine D2/D3 Receptor Availability is Associated with Steep Discounting of Delayed Rewards in Methamphetamine Dependence.

BackgroundIndividuals with substance use disorders typically exhibit a predilection toward instant gratification with apparent disregard for the future consequences of their actions. Indirect evidence suggests that low dopamine D2-type receptor availability in the striatum contributes to the propensity of these individuals to sacrifice long-term goals for short-term gain; however, this possibility has not been tested directly. We investigated whether striatal D2/D3 receptor availability is negatively correlated with the preference for smaller, more immediate rewards over larger, delayed alternatives among research participants who met DSM-IV criteria for methamphetamine (MA) dependence.MethodsFifty-four adults (n = 27 each: MA-dependent, non-user controls) completed the Kirby Monetary Choice Questionnaire, and underwent positron emission tomography scanning with [(18)F]fallypride.ResultsMA users displayed steeper temporal discounting (p = 0.030) and lower striatal D2/D3 receptor availability (p < 0.0005) than controls. Discount rate was negatively correlated with striatal D2/D3 receptor availability, with the relationship reaching statistical significance in the combined sample (r = -0.291, p = 0.016) and among MA users alone (r = -0.342, p = 0.041), but not among controls alone (r = -0.179, p = 0.185); the slopes did not differ significantly between MA users and controls (p = 0.5).ConclusionsThese results provide the first direct evidence of a link between deficient D2/D3 receptor availability and steep temporal discounting. This finding fits with reports that low striatal D2/D3 receptor availability is associated with a higher risk of relapse among stimulant users, and may help to explain why some individuals choose to continue using drugs despite knowledge of their eventual negative consequences. Future research directions and therapeutic implications are discussed

Improving quality of life for people with dementia in care homes: Making psychosocial interventions work

This is the author accepted manuscript. The final version is available from Cambridge University Press via the DOI in this recordPsychosocial interventions can improve behaviour and mood in people with dementia, but it is unclear how to maximise their effectiveness or acceptability in residential settings. Aims To understand what underlies the successful implementation of psychosocial interventions in care homes. Method Systematic review and meta-synthesis of qualitative research. Results The synthesis of 39 qualitative papers revealed that beneficial psychosocial interventions met the needs of people with dementia to connect with others, make a meaningful contribution and reminisce. Successful implementation rested on the active engagement of staff and family and the continuing provision of tailored interventions and support. This necessitated staff time, and raised issues around priorities and risk, but ultimately helped redefine staff attitudes towards residents and the caregiving role. Conclusions The findings from the meta-synthesis can help to inform the development and evaluation of psychosocial interventions in care homes and support their widespread implementation in clinical settings.National Institute for Health Research (NIHR

Run-in periods and clinical outcomes of antipsychotics in dementia:A meta-epidemiological study of placebo-controlled trials

PURPOSE: Run-in periods are used to identify placebo-responders and washout. Our aim was to assess the association of run-in periods with clinical outcomes of antipsychotics in dementia. METHODS: We searched randomized placebo-controlled trials of conventional and atypical antipsychotics for neuropsychiatric symptoms (NPS) in dementia in electronic sources and references of selected articles. We extracted (a) the presence of a run-in period, use of placebo/investigated drug during run-in (versus washout only), and run-in duration (1 week or more) and (b) the reduction in NPS, number of participants with somnolence, extrapyramidal symptoms (EPS), and deaths per treatment group. We pooled clinical outcomes comparing antipsychotic and placebo groups in trials with and without run-in. RESULTS: We identified 35 trials. Twenty-nine trials used run-in. The pooled standardized mean difference in the reduction of NPS was -0.170 (95% CI, -0.227 to -0.112) in trials with run-in and -0.142 (95% CI, -0.331 to 0.047) in trials without run-in. The pooled odds ratio for somnolence was 2.8 (95% CI, 2.3-3.5) in trials with run-in and 3.5 (95% CI, 1.2-10.7) in trials without run-in; for EPS, these ORs were 1.8 (95% CI, 1.4-2.2) and 2.0 (95% CI, 1.3-3.1) respectively, and for mortality 1.4 (95% CI, 1.0-2.0) and 1.6 (95% CI, 0.7-3.4). The use of placebo/investigated drug during run-in and run-in duration did not affect the estimates in a consistent way. CONCLUSIONS: The use of run-in in trials might have led to overestimated efficacy and especially underestimated risks of side effects of antipsychotics compared with placebo for NPS in dementia

Adaptive Optics Images of Kepler Objects of Interest

All transiting planets are at risk of contamination by blends with nearby, unresolved stars. Blends dilute the transit signal, causing the planet to appear smaller than it really is, or produce a false positive detection when the target star is blended with eclipsing binary stars. This paper reports on high spatial-resolution adaptive optics images of 90 Kepler planetary candidates. Companion stars are detected as close as 0.1 arcsec from the target star. Images were taken in the near-infrared (J and Ks bands) with ARIES on the MMT and PHARO on the Palomar Hale 200-inch. Most objects (60%) have at least one star within 6 arcsec separation and a magnitude difference of 9. Eighteen objects (20%) have at least one companion within 2 arcsec of the target star; 6 companions (7%) are closer than 0.5 arcsec. Most of these companions were previously unknown, and the associated planetary candidates should receive additional scrutiny. Limits are placed on the presence of additional companions for every system observed, which can be used to validate planets statistically using the BLENDER method. Validation is particularly critical for low-mass, potentially Earth-like worlds, which are not detectable with current-generation radial velocity techniques. High-resolution images are thus a crucial component of any transit follow-up program.Comment: 9 pages, 4 figures, accepted to A

Gravitational imaging through a triple source plane lens: revisiting the Λ\LambdaCDM-defying dark subhalo in SDSSJ0946+1006

The $\Lambda$CDM paradigm successfully explains the large-scale structure of the Universe, but is less well constrained on sub-galactic scales. Gravitational lens modelling has been used to measure the imprints of dark substructures on lensed arcs, testing the small-scale predictions of $\Lambda$CDM. However, the methods required for these tests are subject to degeneracies among the lens mass model and the source light profile. We present a case study of the unique compound gravitational lens SDSSJ0946+1006, wherein a dark, massive substructure has been detected, whose reported high concentration would be unlikely in a $\Lambda$CDM universe. For the first time, we model the first two background sources in both I- and U-band HST imaging, as well as VLT-MUSE emission line data for the most distant source. We recover a lensing perturber at a $5.9\sigma$ confidence level with mass $\log_{10}(M_\mathrm{sub}/M_{\odot})=9.2^{+0.4}_{-0.1}$ and concentration $\log_{10}c=2.4^{+0.5}_{-0.3}$. The concentration is more consistent with CDM subhalos than previously reported, and the mass is compatible with that of a dwarf satellite galaxy whose flux is undetectable in the data at the location of the perturber. A wandering black hole with mass $\log_{10}(M_\mathrm{BH}/M_{\odot})=8.9^{+0.2}_{-0.1}$ is a viable alternative model. We systematically investigate alternative assumptions about the complexity of the mass distribution and source reconstruction; in all cases the subhalo is detected at around the $\geq5\sigma$ level. However, the detection significance can be altered substantially (up to $11.3\sigma$) by alternative choices for the source regularisation scheme.Comment: 23 pages, 16 figures, 5 appendice

Inhaled nitric oxide in premature infants: effect on tracheal aspirate and plasma nitric oxide metabolites

ObjectiveInhaled nitric oxide (iNO) is a potential new therapy for prevention of bronchopulmonary dysplasia and brain injury in premature infants. This study examined dose-related effects of iNO on NO metabolites as evidence of NO delivery.Study designA subset of 102 premature infants in the NO CLD trial, receiving 24 days of iNO (20 p.p.m. decreasing to 2 p.p.m.) or placebo, were analyzed. Tracheal aspirate (TA) and plasma samples collected at enrollment and at intervals during study gas were analyzed for NO metabolites.ResultiNO treatment increased NO metabolites in TA at 20 and 10 p.p.m. (1.7- to 2.3-fold vs control) and in plasma at 20, 10, and 5 p.p.m. (1.6- to 2.3-fold). In post hoc analysis, treated infants with lower metabolite levels at entry had an improved clinical outcome.ConclusioniNO causes dose-related increases in NO metabolites in the circulation as well as lung fluid, as evidenced by TA analysis, showing NO delivery to these compartments

Phonon downconversion to suppress correlated errors in superconducting qubits

Quantum error correction can preserve quantum information in the presence of local errors, but correlated errors are fatal. For superconducting qubits, high-energy particle impacts from background radioactivity produce energetic phonons that travel throughout the substrate and create excitations above the superconducting ground state, known as quasiparticles, which can poison all qubits on the chip. We use normal metal reservoirs on the chip back side to downconvert phonons to low energies where they can no longer poison qubits. We introduce a pump-probe scheme involving controlled injection of pair-breaking phonons into the qubit chips. We examine quasiparticle poisoning on chips with and without back-side metallization and demonstrate a reduction in the flux of pair-breaking phonons by over a factor of 20. We use a Ramsey interferometer scheme to simultaneously monitor quasiparticle parity on three qubits for each chip and observe a two-order of magnitude reduction in correlated poisoning due to background radiation.Comment: 24 pages, 17 figures, 5 table

Caribou Distribution During the Post-calving Period in Relation to Infrastructure in the Prudhoe Bay Oil Field, Alaska

There is concern that caribou (Rangifer tarandus) may avoid roads and facilities (i.e. infrastructure) in the Prudhoe Bay oil field (PBOF) in northern Alaska, and that this avoidance can have negative effects on the animals. We quantified the relationship between caribou distribution and PBOF infrastructure during the post-calving period (mid-June to mid-August) with aerial surveys from 1990 to 1995. We conducted four to eight surveys per year with complete coverage of the PBOF. We identified active oil field infrastructure and used a geographic information system (GIS) to construct ten 1 km wide concentric intervals surrounding the infrastructure. We tested whether caribou distribution is related to distance from infrastructure with a chi-squared habitat utilization-availability analysis and log-linear regression. We considered bull, calves, and total caribou of all sex/age classes separately. The habitat utilization-availability analysis indicated there was no consistent trend of attraction to or avoidance of infrastructure. Caribou frequently were more abundant than expected in the intervals close to infrastructure, and this trend was more pronounced for bulls and for total caribou of all sex/age classes than for calves. Log-linear regression (with Poisson error structure) of numbers of caribou and distance from infrastructure were also done, with and without combining data into the 1 km distance intervals. The analysis without intervals revealed no relationship between caribou distribution and distance from oil field infrastructure, or between caribou distribution and Julian date, year, or distance from the Beaufort Sea coast. The log-linear regression with caribou combined into distance intervals showed the density of bulls and total caribou of all sex/age classes declined with distance from infrastructure. Our results indicate that during the post-calving period: 1) caribou distribution is largely unrelated to distance from infrastructure; 2) caribou regularly use habitats in the PBOF; 3) caribou often occur close to infrastructure; and 4) caribou do not appear to avoid oil field infrastructure.On s'inquiète du fait que le caribou (Rangifer tarandus) pourrait éviter les routes et installations (c-à-d. les infrastructures) du champ pétrolifère de Prudhoe Bay dans l'Alaska septentrional et que ce comportement pourrait avoir des répercussions négatives sur les animaux. Des relevés aériens effectués de 1990 à 1995 ont permis de quantifier le rapport entre la distribution du caribou et les infrastructures du champ pétrolifère de Prudhoe Bay au cours de la période suivant immédiatement la mise bas (de mi-juin à mi-août). On a procédé à un nombre de relevés annuels allant de quatre à huit, couvrant toute la superficie du champ. On a identifié les infrastructures du champ pétrolifère qui étaient en activité et utilisé un système d'information géographique (SIG) pour construire dix anneaux concentriques de 1 km de large entourant chaque infrastructure. On a testé l'hypothèse que la distribution du caribou est indépendante de l'éloignement de l'infrastructure grâce au test de chi carré entre l'utilisation et la disponibilité de l'habitat, et à la régression log-linéaire. On a tenu compte séparément de la catégorie des mâles, de celle des veaux et de celle de la population totale, sexe et âge confondus. L'analyse de l'utilisation et de la disponibilité de l'habitat révélait qu'il n'y avait pas de schéma cohérent d'attrait ou d'évitement des infrastructures. Les caribous étaient souvent plus abondants que prévu dans les anneaux proches des infrastructures, et cette tendance était plus prononcée pour les mâles adultes et pour l'ensemble des catégories, sexe et âge confondus, que pour les veaux. On a fait les analyses par régression log-linéaire en regroupant et sans regrouper les données anneaux de 1 km de largeur. L'analyse sans regroupement montrait qu'il n'existe pas de rapport entre la distribution du caribou et l'éloignement des infrastructures du champ pétrolifère, ou entre la distribution du caribou et la date julienne ou même l'éloignement de la côte de la mer de Beaufort. L'analyse log-linéaire avec les caribous regroupés dans des anneaux concentriques montrait que la densité des mâles adultes de l'ensemble de la population, sexe et âge confondus, était plus élevée dans les anneaux jouxtant les infrastructures. Nos résultats indiquent que, durant la période suivant immédiatement la mise bas: (1) la distribution du caribou est dans une large mesure indépendante de l'éloignement des infrastructures; (2) le caribou utilise les habitats au sein du champ pétrolifère de Prudhoe Bay sur une base régulière; (3) le caribou se trouve fréquemment près des infrastructures; et (4) le caribou ne semble pas chercher à éviter les infrastructures du champ pétrolifère