Operation of a high purity germanium crystal in liquid argon as a Compton suppressed radiation spectrometer

A high purity germanium crystal was operated in liquid argon as a Compton suppressed radiation spectrometer. Spectroscopic quality resolution of less than 1% of the full-width half maximum of full energy deposition peaks was demonstrated. The construction of the small apparatus used to obtain these results is reported. The design concept is to use the liquid argon bath to both cool the germanium crystal to operating temperatures and act as a scintillating veto. The scintillation light from the liquid argon can veto cosmic-rays, external primordial radiation, and gamma radiation that does not fully deposit within the germanium crystal. This technique was investigated for its potential impact on ultra-low background gamma-ray spectroscopy. This work is based on a concept initially developed for future germanium-based neutrinoless double-beta decay experiments.Comment: Paper presented at the SORMA XI Conference, Ann Arbor, MI, May 200

REMCARE : pragmatic multi-centre randomised trial of reminiscence groups for people with dementia and their family carers : effectiveness and economic analysis

Background Joint reminiscence groups, involving people with dementia and family carers together, are popular, but the evidence-base is limited. This study aimed to assess the effectiveness and cost-effectiveness of joint reminiscence groups as compared to usual care. Methods This multi-centre, pragmatic randomised controlled trial had two parallel arms: intervention group and usual-care control group. A restricted dynamic method of randomisation was used, with an overall allocation ratio of 1:1, restricted to ensure viable sized intervention groups. Assessments, blind to treatment allocation, were carried out at baseline, three months and ten months (primary end-point), usually in the person's home. Participants were recruited in eight centres, mainly through NHS Memory Clinics and NHS community mental health teams. Included participants were community resident people with mild to moderate dementia (DSM-IV), who had a relative or other care-giver in regular contact, to act as informant and willing and able to participate in intervention. 71% carers were spouses. 488 people with dementia (mean age 77.5) were randomised: 268 intervention, 220 control; 350 dyads completed the study (206 intervention, 144 control). The intervention evaluated was joint reminiscence groups (with up to 12 dyads) weekly for twelve weeks; monthly maintenance sessions for further seven months. Sessions followed a published treatment manual and were held in a variety of community settings. Two trained facilitators in each centre were supported by volunteers. Primary outcome measures were self-reported quality of life for the person with dementia (QoL-AD), psychological distress for the carer (General Health Questionnaire, GHQ-28). Secondary outcome measures included: autobiographical memory and activities of daily living for the person with dementia; carer stress for the carer; mood, relationship quality and service use and costs for both. Results The intention to treat analysis (ANCOVA) identified no differences in outcome between the intervention and control conditions on primary or secondary outcomes (self-reported QoL-AD mean difference 0.07 (-1.21 to 1.35), F = 0.48, p = 0.53). Carers of people with dementia allocated to the reminiscence intervention reported a significant increase in anxiety on a General Health Questionnaire-28 sub-scale at the ten month end-point (mean difference 1.25 (0.25 to 2.26), F = 8.28, p = 0.04). Compliance analyses suggested improved autobiographical memory, quality of life and relationship quality for people with dementia attending more reminiscence sessions, however carers attending more groups showed increased care-giving stress. Economic analyses from a public sector perspective indicated that joint reminiscence groups are unlikely to be cost-effective. There were no significant adverse effects attributed to the intervention. Potential limitations of the study include less than optimal attendance at the group sessions—only 57% of participants attended at least half of the intervention sessions over the 10 month period, and a higher rate of study withdrawal in the control group. Conclusions This trial does not support the clinical effectiveness or cost-effectiveness of joint reminiscence groups. Possible beneficial effects for people with dementia who attend sessions as planned are offset by raised anxiety and stress in their carers. The reasons for these discrepant outcomes need to be explored further, and may necessitate reappraisal of the movement towards joint interventions

A Phase 2b randomised, controlled, partially blinded trial of the HIV Nucleoside Reverse Transcriptase Inhibitor BMS-986001 (AI467003): Weeks 24 and 48 Efficacy, Safety, Bone and Metabolic Results

Background BMS-986001 is a thymidine analogue nucleoside reverse transcriptase inhibitor (NRTI) designed to maintain in-vitro antiviral activity while minimising off-target effects. We assessed the efficacy and safety of BMS-986001 versus tenofovir disoproxil fumarate in treatment-naive patients with HIV-1. Methods In this phase 2b, randomised, active-controlled trial (AI467003), we recruited treatment-naive (no current or previous exposure to an antiretroviral drug for >1 week) adults (aged at least 18 years) with HIV-1 from 47 sites across Asia, Australia, Europe, North America, South Africa, and South America. Patients with plasma HIV-1 RNA greater than 5000 copies per mL and CD4 counts greater than 200 cells per μL were randomly assigned (2:2:2:3) to receive BMS-986001 100 mg, 200 mg, or 400 mg once a day or to receive tenofovir disoproxil fumarate 300 mg once a day; each allocation was given with efavirenz 600 mg once a day and lamivudine 300 mg once a day. Both patients and investigators were masked to BMS-986001 dose (achieved with similar looking placebo tablets), but not allocation up to and including week 48. The primary endpoints were the proportion of patients with plasma HIV-1 RNA less than 50 copies per mL and safety events (serious adverse events and adverse events leading to discontinuation) through week 24; the main analysis was with a modified intention-to-treat population. Resistance analysis was a secondary endpoint, and additional safety parameters were exploratory endpoints. This trial is registered with ClinicalTrials.gov, number NCT01489046, and the European Clinical Trials Database, number EudraCT 2011-003329-89. Findings Patients were recruited between Jan 25, 2012, and Oct 3, 2012; 757 patients were assessed for eligibility and 301 were randomly assigned to receive either BMS-986001 once a day (67 patients to 100 mg, 67 to 200 mg, and 66 to 400 mg) or tenofovir disoproxil fumarate (n=101). 297 patients received at least one dose of study drug. At week 24, 57 (88%) of 65 patients for whom there were data in the 100 mg group, 54 (81%) of 67 in the 200 mg group, 62 (94%) of 66 in the 400 mg group achieved HIV-1 RNA less than 50 copies per mL, compared with 88 (89%) of 99 in the tenofovir disoproxil fumarate group (modified intention-to-treat population). BMS-986001 was generally well tolerated through week 48. Two patients had BMS-986001-related serious adverse events (atypical drug eruption and thrombocytopenia) and two in the tenofovir disoproxil fumarate group had study drug-related serious adverse events (potential drug-induced liver injury and depression or lipodystrophy) that led to discontinuation. NRTI resistance-associated mutations were reported in four (2%) of 198 patients, and non-NRTI mutations in 17 (9%) of 198 patients receiving BMS-986001 versus none of 99 and one (1%) of 99 patients receiving tenofovir disoproxil fumarate, respectively. Compared with tenofovir disoproxil fumarate, individuals in the BMS-986001 groups showed a smaller decrease in lumbar spine and hip bone mineral density but greater accumulation of limb and trunk fat, subcutaneous and visceral adipose tissue, and increased total cholesterol. Interpretation BMS-986001 had similar efficacy to that of tenofovir disoproxil fumarate and was associated with a smaller decrease in bone mineral density; however, greater resistance and gains in both peripheral and central fat accumulation were recorded for the investigational drug. Bristol-Myers Squibb has discontinued its involvement in the development of BMS-986001, and future decisions on development will be made by Oncolys BioPharma

Measurement and modeling of cosmic ray exposure for SuperCDMS dark matter detectors.

Dark matter is an unknown type of matter that composes roughly 27% of the observable universe and, as cosmological structure models suggest, the earth should be passing through a “dark halo” of this unknown matter present in the Milky Way galaxy. As we pass through this halo, the Super Cryogenic Dark Matter Search (SuperCDMS) experiment aims to directly detect dark -matter particles. Though many dark matter particle candidates exist, SuperCDMS focuses on the detection of particles called WIMPS (weakly interacting massive particles) as predicted by super-symmetric theories beyond the standard model. Due to the high-sensitivity of the germanium detectors employed, shielding from cosmic rays is paramount, thus the measurements will be performed 6561 feet below ground at SNOLAB. While the experiment will be performed underground, fabrication of the germanium detectors will occur above ground. During this fabrication period, the germanium detectors are exposed to cosmic ray secondaries (i.e., neutrons, protons, and muons). These high-energy secondary particles can interact with the germanium nuclei in the detector crystals through a spallation process that breaks apart the nuclei resulting in unstable products. Of particular concern is the production of tritum that has a ling, 12 year half-life. The eventual beta decay of tritium will create a background contribution that diminishes the sensitivity to WIMP detection. A goal of this work is to model and predict cosmogenic exposure at the fabrication sites to account for this tritium production. Expected integrated cosmic ray fluxes were derived for three cosmic ray particles: secondary muons, protons, and neutrons, at ten different fabrication and experimental sites involved in the SuperCDMS experiment. In addition to the cosmic ray fluxes, location and time depend cosmic ray attenuation parameters were developed to account for three main variables: elevation, position with respect to the earth’s magnetic field, as well as time of exposure with respect to the sun’s 11 year solar cycle. In addition, for each of the ten fabrication sites a CRY simulation was developed and run to predict the constituent cosmic ray flux for each particle. A portable cosmic-ray muon detector will be shipped to each site to gather cosmic-ray exposure to confirm these predictions. This detector was assembled and cosmic ray fluxes were measured above ground at PNNL as well as in PNNL’s shallow underground laboratory

Design and Fabrication of Liquid Scintillator Counter

Pacific Northwest National Laboratory (PNNL) is currently developing an ultra-low background liquid scintillator counter (ULB LSC) in the shallow underground laboratory. At a depth of 35-meters water-equivalent, the underground laboratory has a multi-layered shielding to keep out cosmic-ray induced background. The ULB LSC, which is located in a clean room facility, is a multi-layered design made up of various materials, including plastic scintillator veto panels, borated polyethylene, lead and copper. These layers help lower the contributions of the terrestrial background and intrinsic background, resulting from the impurities present in the materials, to the overall background count rate observed by the detectors. After the completion of the instrument, the first liquid scintillation sample will be tested using a pulley-like design. The design consists of a sample holder which holds the vial in place as it is lowered down into a light guide. The second component of the design is a piece which helps lower the sample holder in the correct orientation into the light guide in order to maximize light output and collection efficiency. The system is designed using Solidworks, a computer aided design (CAD) program, and 3D printed using Acrylonitrile Butadiene Styrene (ABS) plastic. The design for the sample holder is based off of another more complex design originally made of copper. This simplified sample handling design will accelerate the project toward initial data collection, an important milestone toward validating the UBL LSC system concept