Open Dialogue compared to treatment as usual for adults experiencing a mental health crisis: Protocol for the ODDESSI multi-site cluster randomised controlled trial.

Background 'Open Dialogue' is a social network model of crisis and continuing mental healthcare which involves elements of service delivery such as immediate response and a style of therapeutic meeting called network meetings. Although there are indications from non-randomised studies that it may help people in their recovery from severe mental health crises and improve long-term outcomes, this has yet to be tested in a randomised controlled trial. Methods This paper outlines the protocol for a multi-site cluster-randomised control trial assessing the clinical and cost-effectiveness of Open Dialogue compared to treatment as usual (TAU) for individuals presenting in crisis to six mental health services in England. The primary outcome is time to relapse, with secondary outcomes including measures of recovery and service use. Participants will be followed-up for two years, with data collected from electronic medical records and researcher-led interviews. The analysis will compare outcomes between treatment groups as well as investigating potential mediators of effect: shared decision-making and social network quality and size. Carers of a subsample of participants will be asked about their experiences of shared decision-making, carer burden, and satisfaction. Discussion This trial will provide evidence of whether Open Dialogue services implemented in the English mental health system is an effective alternative to current care and may have important implications for the organization of community mental health services. Trial registration: retrospectively registered (108 participants recruited of 570 target) on 20/12/2019, ISRCTN52653325. [Abstract copyright: Copyright © 2021. Published by Elsevier Inc.

A randomised controlled trial of the clinical and cost-effectiveness of a contingency management intervention for reduction of cannabis use and of relapse in early psychosis (CIRCLE): a study protocol for a randomised controlled trial

Background: Around 35–45 % of people in contact with services for a first episode of psychosis are using cannabis. Cannabis use is associated with delays in remission, poorer clinical outcomes, significant increases in the risk of relapse, and lower engagement in work or education. While there is a clear need for effective interventions, so far only very limited benefits have been achieved from psychological interventions. Contingency management (CM) is a behavioural intervention in which specified desired behavioural change is reinforced through financial rewards. CM is now recognised to have a substantial evidence base in some contexts and its adoption in the UK is advocated by the National Institute for Health and Care Excellence (NICE) guidance as a treatment for substance or alcohol misuse. However, there is currently little published data testing its effectiveness for reducing cannabis use in early psychosis. Methods: CIRCLE is a two-arm, rater-blinded randomised controlled trial (RCT) investigating the clinical and cost-effectiveness of a CM intervention for reducing cannabis use among young people receiving treatment from UK Early Intervention in Psychosis (EIP) services. EIP service users (n = 544) with a recent history of cannabis use will be recruited. The experimental group will receive 12 once-weekly CM sessions, and a voucher reward if urinalysis shows that they have not used cannabis in the previous week. Both the experimental and the control groups will be offered an Optimised Treatment as Usual (OTAU) psychoeducational package targeting cannabis use. Assessment interviews will be performed at consent, at 3 months, and at 18 months. The primary outcome is time to relapse, defined as admission to an acute mental health service. Secondary outcomes include proportion of cannabis-free urine samples during the intervention period, severity of positive psychotic symptoms, quality-adjusted life years, and engagement in work or education. Discussion: CIRCLE is a RCT of CM for cannabis use in young people with a recent history of psychosis (EIP service users) and recent cannabis use. It is designed to investigate whether the intervention is a clinically and cost-effective treatment for cannabis use. It is intended to inform future treatment delivery, particularly in EIP settings

Finding Concealed Active Faults: Extending the Southern Whidbey Island Fault across the Puget Lowland, Washington

The southern Whidbey Island fault zone (SWIF), as previously mapped using borehole data, potential field anomalies, and marine seismic reflection surveys, consists of three subparallel, northwest trending strands extending ~100 km from near Vancouver Island to the northern Puget Lowland. East of Puget Sound, the SWIF makes landfall between the cities of Seattle and Everett but is concealed beneath a thick mantle of young glacial deposits and vegetation. A ~20-km-wide, northwest trending swath of subparallel, low-amplitude aeromagnetic anomalies crosses this region of the Puget Lowland and is on strike with the SWIF. The most prominent aeromagnetic anomaly, the Cottage Lake lineament, extends at least 18 km and lies approximately on strike with the SWIF on Whidbey Island. Subtle scarps and topographic lineaments on Pleistocene surfaces, visible on high-resolution lidar topography at a number of locations along the SWIF, lie on or near these magnetic anomalies. In the field, scarps exhibit northeast-side-up and vertical relief of 1 to 5 m. Excavations across several lidar scarps lying on or near magnetic anomalies show evidence for multiple folding and faulting events since deglaciation, most likely above buried reverse/oblique faults. Excavations in areas away from magnetic anomalies do not show evidence of tectonic deformation. In total, paleoseismological evidence suggests that the SWIF produced at least four earthquakes since deglaciation about 16,400 years ago, the most recent less than 2700 years ago

Clinical and cost-effectiveness of contingency management for cannabis use in early psychosis: the CIRCLE randomised clinical trial

Cannabis is the most commonly used illicit substance amongst people with psychosis. Continued cannabis use following the onset of psychosis is associated with poorer functional and clinical outcomes. However, finding effective ways of intervening has been very challenging. We examined the clinical and cost-effectiveness of adjunctive contingency management (CM), which involves incentives for abstinence from cannabis use, in people with a recent diagnosis of psychosis. CIRCLE was a pragmatic multi-centre randomised controlled trial. Participants were recruited via Early Intervention in Psychosis (EIP) services across the Midlands and South East of England. They had had at least one episode of clinically diagnosed psychosis (affective or non-affective); were aged 18 to 36; reported cannabis use in at least 12 out of the previous 24 weeks; and were not currently receiving treatment for cannabis misuse, or subject to a legal requirement for cannabis testing. Participants were randomised via a secure web-based service 1:1 to either an experimental arm, involving 12 weeks of CM plus a six-session psychoeducation package, or a control arm receiving the psychoeducation package only. The total potential voucher reward in the CM intervention was £240. The primary outcome was time to acute psychiatric care, operationalised as admission to an acute mental health service (including community alternatives to admission). Primary outcome data were collected from patient records at 18 months post-consent by assessors masked to allocation. The trial was registered with the ISRCTN registry, number ISRCTN33576045. Five hundred fifty-one participants were recruited between June 2012 and April 2016. Primary outcome data were obtained for 272 (98%) in the CM (experimental) group and 259 (95%) in the control group. There was no statistically significant difference in time to acute psychiatric care (the primary outcome) (HR 1.03, 95% CI 0.76, 1.40) between groups. By 18 months, 90 (33%) of participants in the CM group, and 85 (30%) of the control groups had been admitted at least once to an acute psychiatric service. Amongst those who had experienced an acute psychiatric admission, the median time to admission was 196 days (IQR 82, 364) in the CM group and 245 days (IQR 99, 382) in the control group. Cost-effectiveness analyses suggest that there is an 81% likelihood that the intervention was cost-effective, mainly resulting from higher mean inpatient costs for the control group compared with the CM group; however, the cost difference between groups was not statistically significant. There were 58 adverse events, 27 in the CM group and 31 in the control group. Overall, these results suggest that CM is not an effective intervention for improving the time to acute psychiatric admission or reducing cannabis use in psychosis, at least at the level of voucher reward offered

Discovery, Characterization, and Structure–Activity Relationships of an Inhibitor of Inward Rectifier Potassium (Kir) Channels with Preference for Kir2.3, Kir3.X, and Kir7.1

The inward rectifier family of potassium (Kir) channels is comprised of at least 16 family members exhibiting broad and often overlapping cellular, tissue, or organ distributions. The discovery of disease-causing mutations in humans and experiments on knockout mice has underscored the importance of Kir channels in physiology and in some cases raised questions about their potential as drug targets. However, the paucity of potent and selective small-molecule modulators targeting specific family members has with few exceptions mired efforts to understand their physiology and assess their therapeutic potential. A growing body of evidence suggests that G protein-coupled inward rectifier K (GIRK) channels of the Kir3.X subfamily may represent novel targets for the treatment of atrial fibrillation. In an effort to expand the molecular pharmacology of GIRK, we performed a thallium (Tl+) flux-based high-throughput screen of a Kir1.1 inhibitor library for modulators of GIRK. One compound, termed VU573, exhibited 10-fold selectivity for GIRK over Kir1.1 (IC50 = 1.9 and 19 μM, respectively) and was therefore selected for further study. In electrophysiological experiments performed on Xenopus laevis oocytes and mammalian cells, VU573 inhibited Kir3.1/3.2 (neuronal GIRK) and Kir3.1/3.4 (cardiac GIRK) channels with equal potency and preferentially inhibited GIRK, Kir2.3, and Kir7.1 over Kir1.1 and Kir2.1.Tl+ flux assays were established for Kir2.3 and the M125R pore mutant of Kir7.1 to support medicinal chemistry efforts to develop more potent and selective analogs for these channels. The structure–activity relationships of VU573 revealed few analogs with improved potency, however two compounds retained most of their activity toward GIRK and Kir2.3 and lost activity toward Kir7.1. We anticipate that the VU573 series will be useful for exploring the physiology and structure–function relationships of these Kir channels

Stellar Structure Modeling using a Parallel Genetic Algorithm for Objective Global Optimization

Genetic algorithms are a class of heuristic search techniques that apply basic evolutionary operators in a computational setting. We have designed a fully parallel and distributed hardware/software implementation of the generalized optimization subroutine PIKAIA, which utilizes a genetic algorithm to provide an objective determination of the globally optimal parameters for a given model against an observational data set. We have used this modeling tool in the context of white dwarf asteroseismology, i.e., the art and science of extracting physical and structural information about these stars from observations of their oscillation frequencies. The efficient, parallel exploration of parameter-space made possible by genetic-algorithm-based numerical optimization led us to a number of interesting physical results: (1) resolution of a hitherto puzzling discrepancy between stellar evolution models and prior asteroseismic inferences of the surface helium layer mass for a DBV white dwarf; (2) precise determination of the central oxygen mass fraction in a white dwarf star; and (3) a preliminary estimate of the astrophysically important but experimentally uncertain rate for the ^12C(alpha,gamma)^16O nuclear reaction. These successes suggest that a broad class of computationally-intensive modeling applications could also benefit from this approach.Comment: 22 pages, minor changes, to appear in Journal of Computational Physics (JCPH2002-0129), software available at http://whitedwarf.org/parallel

Clinical consensus statement: Diagnosis and management of nasal valve compromise

OBJECTIVE: To create a clinical consensus statement to address ambiguities and disparities in the diagnosis and management of nasal valve compromise (NVC). SUBJECTS AND METHODS: An updated systematic review of the literature was conducted. In addition, a Modified Delphi Method was used to refine expert opinion and facilitate a consensus position. RESULTS: After two rounds of surveys and conference calls, 36 items reached consensus, six items reached near consensus, and 10 items reached no consensus. The categories that had the greatest percentage of consensus or near consensus items were as follows: definition, history and physical examination, outcome measures, and management. Conversely, the categories with greater percentage of no consensus items were adjunctive tests and coding. CONCLUSION: The consensus panel agreed that NVC is a distinct clinical entity that is best evaluated with history and physical examination findings. Endoscopy and photography are useful but not routinely indicated, whereas radiographic studies are not useful in evaluating NVC. Other objective nasal outcome measures may not be useful or accepted for NVC. Nasal steroid medication is not useful for treatment of NVC in the absence of rhinitis, and mechanical treatments may be useful in selected patients. Surgical treatment is the primary mode of treatment of NVC, but bill coding remains ambiguous and confusing

The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey: Baryon Acoustic Oscillations in the Data Release 9 Spectroscopic Galaxy Sample

We present measurements of galaxy clustering from the Baryon Oscillation Spectroscopic Survey (BOSS), which is part of the Sloan Digital Sky Survey III (SDSS-III). These use the Data Release 9 (DR9) CMASS sample, which contains 264,283 massive galaxies covering 3275 square degrees with an effective redshift z=0.57 and redshift range 0.43 < z < 0.7. Assuming a concordance Lambda-CDM cosmological model, this sample covers an effective volume of 2.2 Gpc^3, and represents the largest sample of the Universe ever surveyed at this density, n = 3 x 10^-4 h^-3 Mpc^3. We measure the angle-averaged galaxy correlation function and power spectrum, including density-field reconstruction of the baryon acoustic oscillation (BAO) feature. The acoustic features are detected at a significance of 5\sigma in both the correlation function and power spectrum. Combining with the SDSS-II Luminous Red Galaxy Sample, the detection significance increases to 6.7\sigma. Fitting for the position of the acoustic features measures the distance to z=0.57 relative to the sound horizon DV /rs = 13.67 +/- 0.22 at z=0.57. Assuming a fiducial sound horizon of 153.19 Mpc, which matches cosmic microwave background constraints, this corresponds to a distance DV(z=0.57) = 2094 +/- 34 Mpc. At 1.7 per cent, this is the most precise distance constraint ever obtained from a galaxy survey. We place this result alongside previous BAO measurements in a cosmological distance ladder and find excellent agreement with the current supernova measurements. We use these distance measurements to constrain various cosmological models, finding continuing support for a flat Universe with a cosmological constant.Comment: 33 page

Gravitational Waves From Known Pulsars: Results From The Initial Detector Era

We present the results of searches for gravitational waves from a large selection of pulsars using data from the most recent science runs (S6, VSR2 and VSR4) of the initial generation of interferometric gravitational wave detectors LIGO (Laser Interferometric Gravitational-wave Observatory) and Virgo. We do not see evidence for gravitational wave emission from any of the targeted sources but produce upper limits on the emission amplitude. We highlight the results from seven young pulsars with large spin-down luminosities. We reach within a factor of five of the canonical spin-down limit for all seven of these, whilst for the Crab and Vela pulsars we further surpass their spin-down limits. We present new or updated limits for 172 other pulsars (including both young and millisecond pulsars). Now that the detectors are undergoing major upgrades, and, for completeness, we bring together all of the most up-to-date results from all pulsars searched for during the operations of the first-generation LIGO, Virgo and GEO600 detectors. This gives a total of 195 pulsars including the most recent results described in this paper.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyAustralian Research CouncilInternational Science Linkages program of the Commonwealth of AustraliaCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Economia y CompetitividadConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsNetherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFOCUS Programme of Foundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space AdministrationOTKA of HungaryLyon Institute of Origins (LIO)National Research Foundation of KoreaIndustry CanadaProvince of Ontario through the Ministry of Economic Development and InnovationNational Science and Engineering Research Council CanadaCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationAstronom

Clinical and cost-effectiveness of contingency management for cannabis use in early psychosis: the CIRCLE randomised clinical trial

Background Cannabis is the most commonly used illicit substance among people with psychosis. Continued cannabis use following the onset of psychosis is associated with poorer functional and clinical outcomes. However, finding effective ways of intervening has been very challenging. We examined the clinical and cost-effectiveness of adjunctive contingency management (CM), which involves incentives for abstinence from cannabis use, in people with a recent diagnosis of psychosis. Methods CIRCLE was a pragmatic multi-centre randomised controlled trial. Participants were recruited via Early Intervention in Psychosis (EIP) services across the Midlands and South East of England. They had had at last one episode of clinically diagnosed psychosis (affective or non-affective); were aged 18 to 36; reported cannabis use in at least 12 out of the previous 24 weeks; and were not currently receiving treatment for cannabis misuse, or subject to a legal requirement for cannabis testing. Participants were randomised via a secure web-based service 1:1 to either an experimental arm, involving 12 weeks of CM plus a six-session psychoeducation package, or a control arm receiving the psychoeducation package only. The total potential voucher reward in the CM intervention was £240. The primary outcome was time to acute psychiatric care, operationalised as admission to an acute mental health service (including community alternatives to admission). Primary outcome data were collected from patient records at 18 months post-consent by assessors masked to allocation. The trial was registered with the ISRCTN registry, number ISRCTN33576045. Results: 551 participants were recruited between June 2012 and April 2016. Primary outcome data were obtained for 272 (98%) in the CM (experimental) group and 259 (95%) in the control group. There was no statistically significant difference in time to acute psychiatric care (the primary outcome) (HR 1.03, 95% CI 0.76, 1.40) between groups. By 18 months, 90 (33%) of participants in the CM group, and 85 (30%) of the control groups had been admitted at least once to an acute psychiatric service. Amongst those who had experienced an acute psychiatric admission, the median time to admission was 196 days (IQR 82, 364) in the CM group and 245 days (IQR 99,382) in the control group. Cost-effectiveness analyses suggest that there is an 81% likelihood that the intervention was cost-effective, mainly resulting from higher mean inpatient costs for the control group compared with the CM group, however the cost difference between groups was not statistically significant. There were 58 adverse events, 27 in the CM group and 31 in the control group. Conclusions Overall, these results suggest that CM is not an effective intervention for improving the time to acute psychiatric admission or reducing cannabis use in psychosis, at least at the level of voucher reward offered