Technical Equivalency Documentation for a Newly Aquired Alpha Spectroscopy System

The response of a recently acquired Canberra{trademark} Alpha Analyst 'Blue' system (Chamber Number's 173-208) used by the Hazards Control, Radiation Safety Section, WBC/Spectroscopy Team has been studied with respect to an existing Canberra system. The existing Canberra system consists of thirty Alpha Analyst dual chambers Model XXXX comprising a total of sixty detectors (Chambers Number's 101-124 and 137-172). The existing chambers were previously compared to an older system consisting of thirty-six Model 7401 alpha spectrometry chambers (Chamber Number's 1-36) Chambers 101-124 and 137-172 are DOELAP accredited. The older system was previously DOELAP accredited for the routine Alpha Spectroscopy program used in LLNL's in vitro bioassay program. The newly acquired Alpha Analyst system operates on a network with software that controls and performs analysis of the current Alpha Analyst system (Chamber Number's 101-124 and 137-172). This exact same software is used for the current system and the newly acquired system and is DOELAP accredited. This document compares results from the existing Alpha System with the newer Alpha Analyst system

Incomplete inhibition of phosphorylation of 4E-BP1 as a mechanism of primary resistance to ATP-competitive mTOR inhibitors

The mammalian target of rapamycin (mTOR) regulates cell growth by integrating nutrient and growth factor signaling and is strongly implicated in cancer. But mTOR is not an oncogene, and which tumors will be resistant or sensitive to new ATP-competitive mTOR inhibitors now in clinical trials remains unknown. We screened a panel of over 600 human cancer cell lines to identify markers of resistance and sensitivity to the mTOR inhibitor PP242. RAS and PIK3CA mutations were the most significant genetic markers for resistance and sensitivity to PP242, respectively; colon origin was the most significant marker for resistance based on tissue type. Among colon cancer cell lines, those with KRAS mutations were most resistant to PP242, while those without KRAS mutations most sensitive. Surprisingly, cell lines with co-mutation of PIK3CA and KRAS had intermediate sensitivity. Immunoblot analysis of the signaling targets downstream of mTOR revealed that the degree of cellular growth inhibition induced by PP242 was correlated with inhibition of phosphorylation of the translational repressor 4E-BP1, but not ribosomal protein S6. In a tumor growth inhibition trial of PP242 in patient-derived colon cancer xenografts, resistance to PP242 induced inhibition of 4E-BP1 phosphorylation and xenograft growth was again observed in KRAS mutant tumors without PIK3CA co-mutation, compared to KRAS WT controls. We show that, in the absence of PIK3CA co-mutation, KRAS mutations are associated with resistance to PP242 and that this is specifically linked to changes in the level of phosphorylation of 4E-BP1

Power output estimation of a RM3 WEC with HF radar measured complex representative sea states

Wave tank model testing has been widely used to assess the performance of Wave Energy Converters (WEC) in different technology readiness levels (TRL). At early stage the use of simple wave conditions such as regular waves and parametric wave spectrum JONSWAP or Pierson-Moskowitz spectrum is acceptable. However at later stages there is a need to use site specific complex wave conditions representative of potential prototype deployment sites. In previous research, 10 different regrouping methods on HF radar measured wave spectrum were tested to find out the most representative sea states for tank testing. It has been shown that by using the K-means clustering technique, the characteristics of wave conditions can be well preserved [1, 2]. In order to assess the power capture performance of a typical WEC in these representative sea states, the RM3 point absorber has been simulated. By analysing how well the average power output predicted from different representative sea-state selection methods compares with the total power output prediction, it is shown that the non-directional wave spectrum K-means clustering method provides the most representative sea states and, for a point absorber, with a very accurate estimation of the total power output, which is not the case by using a traditional binning method. The importance of using the complex site-specific sea states rather than simplified parametric JONSWAP sea states to obtain the accurate total power estimation has also been shown

Anticipated health behaviour changes and perceived control in response to disclosure of genetic risk of breast and ovarian cancer: a quantitative survey study among women in the UK

BACKGROUND: Genetic risk assessment for breast cancer and ovarian cancer (BCOC) is expected to make major inroads into mainstream clinical practice. It is important to evaluate the potential impact on women ahead of its implementation in order to maximise health benefits, as predictive genetic testing without adequate support could lead to adverse psychological and behavioural responses to risk disclosure. OBJECTIVE: To examine anticipated health behaviour changes and perceived control to disclosure of genetic risk for BCOC and establish demographic and person-specific correlates of adverse anticipated responses in a population-based sample of women. DESIGN: Cross-sectional quantitative survey study carried out by the UK Office for National Statistics in January and March 2014. SETTING: Face-to-face computer-assisted interviews conducted by trained researchers in participants’ homes. PARTICIPANTS: 837 women randomly chosen from households across the UK identified from the Royal Mail’s Postcode Address File. OUTCOME MEASURES: Anticipated health behaviour change and perceived control to disclosure of BCOC risk. RESULTS: In response to a genetic test result, most women (72%) indicated ‘I would try harder to have a healthy lifestyle’, and over half (55%) felt ‘it would give me more control over my life’. These associations were independent of demographic factors or perceived risk of BCOC in Bonferroni-corrected multivariate analyses. However, a minority of women (14%) felt ‘it isn’t worth making lifestyle changes’ and that ‘I would feel less free to make choices in my life’ (16%) in response to BCOC risk disclosure. The former belief was more likely to be held by women who were educated below university degree level (P<0.001) after adjusting for other demographic and person-specific correlates. CONCLUSION: These findings indicate that women in the UK largely anticipate that they would engage in positive health behaviour changes in response to BCOC risk disclosure

Clcn7F318L/+ as a new mouse model of Albers-Schönberg disease

Dominant negative mutations in CLCN7, which encodes a homodimeric chloride channel needed for matrix acidification by osteoclasts, cause Albers-Schönberg disease (also known as autosomal dominant osteopetrosis type 2). More than 25 different CLCN7 mutations have been identified in patients affected with Albers-Schönberg disease, but only one mutation (Clcn7G213R) has been introduced in mice to create an animal model of this disease. Here we describe a mouse with a different osteopetrosis-causing mutation (Clcn7F318L). Compared to Clcn7+/+ mice, 12-week-old Clcn7F318L/+ mice have significantly increased trabecular bone volume, consistent with Clcn7F318L acting as a dominant negative mutation. Clcn7F318L/F318L and Clcn7F318L/G213R mice die by 1 month of age and resemble Clcn7 knockout mice, which indicate that p.F318L mutant protein is non-functional and p.F318L and p.G213R mutant proteins do not complement one another. Since it has been reported that treatment with interferon gamma (IFN-G) improves bone properties in Clcn7G213R/+ mice, we treated Clcn7F318L/+ mice with IFN-G and observed a decrease in osteoclast number and mineral apposition rate, but no overall improvement in bone properties. Our results suggest that the benefits of IFN-G therapy in patients with Albers-Schönberg disease may be mutation-specific

Multi-centre parallel arm randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based cognitive behavioural approach to managing fatigue in people with multiple sclerosis

Abstract (provisional) Background Fatigue is one of the most commonly reported and debilitating symptoms of multiple sclerosis (MS); approximately two-thirds of people with MS consider it to be one of their three most troubling symptoms. It may limit or prevent participation in everyday activities, work, leisure, and social pursuits, reduce psychological well-being and is one of the key precipitants of early retirement. Energy effectiveness approaches have been shown to be effective in reducing MS-fatigue, increasing self-efficacy and improving quality of life. Cognitive behavioural approaches have been found to be effective for managing fatigue in other conditions, such as chronic fatigue syndrome, and more recently, in MS. The aim of this pragmatic trial is to evaluate the clinical and cost-effectiveness of a recently developed group-based fatigue management intervention (that blends cognitive behavioural and energy effectiveness approaches) compared with current local practice. Methods This is a multi-centre parallel arm block-randomised controlled trial (RCT) of a six session group-based fatigue management intervention, delivered by health professionals, compared with current local practice. 180 consenting adults with a confirmed diagnosis of MS and significant fatigue levels, recruited via secondary/primary care or newsletters/websites, will be randomised to receive the fatigue management intervention or current local practice. An economic evaluation will be undertaken alongside the trial. Primary outcomes are fatigue severity, self-efficacy and disease-specific quality of life. Secondary outcomes include fatigue impact, general quality of life, mood, activity patterns, and cost-effectiveness. Outcomes in those receiving the fatigue management intervention will be measured 1 week prior to, and 1, 4, and 12 months after the intervention (and at equivalent times in those receiving current local practice). A qualitative component will examine what aspects of the fatigue management intervention participants found helpful/unhelpful and barriers to change. Discussion This trial is the fourth stage of a research programme that has followed the Medical Research Council guidance for developing and evaluating complex interventions. What makes the intervention unique is that it blends cognitive behavioural and energy effectiveness approaches. A potential strength of the intervention is that it could be integrated into existing service delivery models as it has been designed to be delivered by staff already working with people with MS. Service users will be involved throughout this research. Trial registration: Current Controlled Trials ISRCTN7651747

Schools and civil society : corporate or community governance

School improvement depends upon mediating the cultural conditions of learning as young people journey between their parochial worlds and the public world of cosmopolitan society. Governing bodies have a crucial role in including or diminishing the representation of different cultural traditions and in enabling or frustrating the expression of voice and deliberation of differences whose resolution is central to the mediation of and responsiveness to learning needs. A recent study of governing bodies in England and Wales argues that the trend to corporatising school governance will diminish the capacity of schools to learn how they can understand cultural traditions and accommodate them in their curricula and teaching strategies. A democratic, stakeholder model remains crucial to the effective practice of governing schools. By deliberating and reconciling social and cultural differences, governance constitutes the practices for mediating particular and cosmopolitan worlds and thus the conditions for engaging young people in their learning, as well as in the preparation for citizenship in civil society

Real-Time Hybrid Testing of a Floating Offshore Wind Turbine Using a Surrogate-Based Aerodynamic Emulator

Abstract Physical modelling of floating offshore wind turbines (FOWTs) is challenging due to the complexities associated with simultaneous application of two different scaling laws, governing the hydrodynamic and aerodynamic loading on the structure. To avoid these issues, this paper presents a real-time hybrid testing strategy in which a feedback-loop, consisting of an on-board fan, and control algorithm, is utilised to emulate the aerodynamic forces acting on the FOWT system. Here, we apply this strategy to a 70th-scale IEA Wind 15MW reference wind turbine mounted on a version of the VolturnUS-S platform. Unlike other similar methods, which directly simulate the aerodynamic loads for the fan’s control using an aerodynamic code running in parallel with the experiment, this example utilises a surrogate model trained on numerical model data calculated in advance. This strategy enables high fidelity numerical model data, or even physical data, to be included in the aerodynamic emulation, by removing the requirement for real-time simulation, and, therefore, potentially enables more accurate loading predictions to be used in the experiments. This paper documents the development of the real-time hybrid testing system in the Coastal Ocean And Sediment Transport (COAST) Laboratory at the University of Plymouth in the U.K., including the hardware, software and instrumentation set-up, and demonstrates the power of the surrogate-based aerodynamic emulator based on numerical data calculated using OpenFAST.</jats:p