The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Glass Furnace Combustion and Melting Research Facility.

The need for a Combustion and Melting Research Facility focused on the solution of glass manufacturing problems common to all segments of the glass industry was given high priority in the earliest version of the Glass Industry Technology Roadmap (Eisenhauer et al., 1997). Visteon Glass Systems and, later, PPG Industries proposed to meet this requirement, in partnership with the DOE/OIT Glass Program and Sandia National Laboratories, by designing and building a research furnace equipped with state-of-the-art diagnostics in the DOE Combustion Research Facility located at the Sandia site in Livermore, CA. Input on the configuration and objectives of the facility was sought from the entire industry by a variety of routes: (1) through a survey distributed to industry leaders by GMIC, (2) by conducting an open workshop following the OIT Glass Industry Project Review in September 1999, (3) from discussions with numerous glass engineers, scientists, and executives, and (4) during visits to glass manufacturing plants and research centers. The recommendations from industry were that the melting tank be made large enough to reproduce the essential processes and features of industrial furnaces yet flexible enough to be operated in as many as possible of the configurations found in industry as well as in ways never before attempted in practice. Realization of these objectives, while still providing access to the glass bath and combustion space for optical diagnostics and measurements using conventional probes, was the principal challenge in the development of the tank furnace design. The present report describes a facility having the requirements identified as important by members of the glass industry and equipped to do the work that the industry recommended should be the focus of research. The intent is that the laboratory would be available to U.S. glass manufacturers for collaboration with Sandia scientists and engineers on both precompetitive basic research and the solution of proprietary glass production problems. As a consequence of the substantial increase in scale and scope of the initial furnace concept in response to industry recommendations, constraints on funding of industrial programs by DOE, and reorientation of the Department's priorities, the OIT Glass Program is unable to provide the support for construction of such a facility. However, it is the present investigators' hope that a group of industry partners will emerge to carry the project forward, taking advantage of the detailed furnace design presented in this report. The engineering, including complete construction drawings, bill of materials, and equipment specifications, is complete. The project is ready to begin construction as soon as the quotations are updated. The design of the research melter closely follows the most advanced industrial practice, firing by natural gas with oxygen. The melting area is 13 ft x 6 ft, with a glass depth of 3 ft and an average height in the combustion space of 3 ft. The maximum pull rate is 25 tons/day, ranging from 100% batch to 100% cullet, continuously fed, with variable batch composition, particle size distribution, and raft configuration. The tank is equipped with bubblers to control glass circulation. The furnace can be fired in three modes: (1) using a single large burner mounted on the front wall, (2) by six burners in a staggered/opposed arrangement, three in each breast wall, and (3) by down-fired burners mounted in the crown in any combination with the front wall or breast-wall-mounted burners. Horizontal slots are provided between the tank blocks and tuck stones and between the breast wall and skewback blocks, running the entire length of the furnace on both sides, to permit access to the combustion space and the surface of the glass for optical measurements and sampling probes. Vertical slots in the breast walls provide additional access for measurements and sampling. The furnace and tank are to be fully instrumented with standard measuring equipment, such as flow meters, thermocouples, continuous gas composition analyzers, optical pyrometers, and a video camera. The output from the instruments is to be continuously recorded and simultaneously made available to other researchers via the Internet. A unique aspect of the research facility would be its access to the expertise in optical measurements in flames and high temperature reacting flows residing in the Sandia Combustion Research Facility. Development of new techniques for monitoring and control of glass melting would be a major focus of the work. The lab would be equipped with conventional and laser light sources and detectors for optical measurements of gas temperature, velocity, and gaseous species and, using new techniques to be developed in the Research Facility itself, glass temperature and glass composition

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

Background: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding: National Institute for Health Research Health Services and Delivery Research Programme

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme

Service user and carer involvement in physiotherapy practice, education and research: getting involved for a change

User involvement has become a dominant discourse in health and social care. Users are patients, carers or clients who are current or recent recipients of a service, or members of the public with an interest in the health of their communities. This distinction underlines the increasing concern of governments to involve citizens both in decisions about their individual care, and in collective decisions about the overall shape of services. Involvement is perceived to widen the views and experience informing decision-making; increase the acceptability of decisions made; and lead to more individual and community responsibility for health (WHO 2006). Physiotherapy forms part of the fabric of health provision and the profession needs to be aware of the drivers for involvement, and to be competent at involvement in all facets of its work.<br/

“Staying safe”–a narrative review of falls prevention in people with Parkinson’s–“PDSAFE”

Background: Parkinson’s disease demonstrates a spectrum of motor and non-motor symptoms. Falling is common and disabling. Current medical management shows minimal impact to reduce falls or fall-related risk factors, such as deficits in gait, strength, and postural instability. Despite evidence supporting rehabilitation in reducing fall risk factors, the most appropriate intervention to reduce overall fall rate remains inconclusive. This article aims to 1) synthesise current evidence and conceptual models of falls rehabilitation in Parkinson’s in a narrative review; and based on this evidence, 2) introduce the treatment protocol used in the falls prevention and multi-centre clinical trial “PDSAFE”. Method: Search of four bibliographic databases using the terms “Parkinson*” and “Fall*” combined with each of the following; “Rehab*, Balanc*, Strength*, Strateg*and Exercis*” and a framework for narrative review was followed. A total of 3557 papers were identified, 416 were selected for review. The majority report the impact of rehabilitation on isolated fall risk factors. Twelve directly measure the impact on overall fall rate. Discussion: Results were used to construct a narrative review with conceptual discussion based on the “International Classification of Functioning”, leading to presentation of the “PDSAFE” intervention protocol. Conclusions: Evidence suggests training single, fall risk factors may not affect overall fall rate. Combining with behavioural and strategy training in a functional, personalised multi-dimensional model, addressing all components of the “International Classification of Functioning” is likely to provide a greater influence on falls reduction. “PDSAFE” is a multi-dimensional, physiotherapist delivered, individually tailored, progressive, home-based programme. It is designed with a strong evidence-based approach and illustrates a model for the clinical delivery of the conceptual theory discussed.Implications for Rehabilitation Parkinson’s disease demonstrates a spectrum of motor and non-motor symptoms, where falling is common and disabling. Current medical and surgical management have minimal impact on falls, rehabilitation of falls risk factors has strong evidence but the most appropriate intervention to reduce overall fall rate remains inconclusive. Addressing all components of the International Classification of Function in a multifactorial model when designing falls rehabilitation interventions may be more effective at reducing fall rates in people with Parkinson’s than treating isolated risk factors. The clinical model for falls rehabilitation in people with Parkinson’s should be multi-dimensional.</p

“Staying safe”–a narrative review of falls prevention in people with Parkinson’s–“PDSAFE”

Background: Parkinson’s disease demonstrates a spectrum of motor and non-motor symptoms. Falling is common and disabling. Current medical management shows minimal impact to reduce falls or fall-related risk factors, such as deficits in gait, strength, and postural instability. Despite evidence supporting rehabilitation in reducing fall risk factors, the most appropriate intervention to reduce overall fall rate remains inconclusive. This article aims to 1) synthesise current evidence and conceptual models of falls rehabilitation in Parkinson’s in a narrative review; and based on this evidence, 2) introduce the treatment protocol used in the falls prevention and multi-centre clinical trial “PDSAFE”. Method: Search of four bibliographic databases using the terms “Parkinson*” and “Fall*” combined with each of the following; “Rehab*, Balanc*, Strength*, Strateg*and Exercis*” and a framework for narrative review was followed. A total of 3557 papers were identified, 416 were selected for review. The majority report the impact of rehabilitation on isolated fall risk factors. Twelve directly measure the impact on overall fall rate. Discussion: Results were used to construct a narrative review with conceptual discussion based on the “International Classification of Functioning”, leading to presentation of the “PDSAFE” intervention protocol. Conclusions: Evidence suggests training single, fall risk factors may not affect overall fall rate. Combining with behavioural and strategy training in a functional, personalised multi-dimensional model, addressing all components of the “International Classification of Functioning” is likely to provide a greater influence on falls reduction. “PDSAFE” is a multi-dimensional, physiotherapist delivered, individually tailored, progressive, home-based programme. It is designed with a strong evidence-based approach and illustrates a model for the clinical delivery of the conceptual theory discussed.Implications for Rehabilitation Parkinson’s disease demonstrates a spectrum of motor and non-motor symptoms, where falling is common and disabling. Current medical and surgical management have minimal impact on falls, rehabilitation of falls risk factors has strong evidence but the most appropriate intervention to reduce overall fall rate remains inconclusive. Addressing all components of the International Classification of Function in a multifactorial model when designing falls rehabilitation interventions may be more effective at reducing fall rates in people with Parkinson’s than treating isolated risk factors. The clinical model for falls rehabilitation in people with Parkinson’s should be multi-dimensional.</p

"Staying safe" - a narrative review of falls prevention in people with Parkinson's - "PDSAFE"

Background: Parkinson's disease demonstrates a spectrum of motor and non-motor symptoms. Falling is common and disabling. Current medical management shows minimal impact to reduce falls or fall-related risk factors, such as deficits in gait, strength, and postural instability. Despite evidence supporting rehabilitation in reducing fall risk factors, the most appropriate intervention to reduce overall fall rate remains inconclusive. This article aims to 1) synthesise current evidence and conceptual models of falls rehabilitation in Parkinson's in a narrative review; and based on this evidence, 2) introduce the treatment protocol used in the falls prevention and multi-centre clinical trial "PDSAFE". Method: Search of four bibliographic databases using the terms "Parkinson*" and "Fall*" combined with each of the following; "Rehab*, Balanc*, Strength*, Strateg*and Exercis*" and a framework for narrative review was followed. A total of 3557 papers were identified, 416 were selected for review. The majority report the impact of rehabilitation on isolated fall risk factors. Twelve directly measure the impact on overall fall rate. Discussion: Results were used to construct a narrative review with conceptual discussion based on the "International Classification of Functioning", leading to presentation of the "PDSAFE" intervention protocol. Conclusions: Evidence suggests training single, fall risk factors may not affect overall fall rate. Combining with behavioural and strategy training in a functional, personalised multi-dimensional model, addressing all components of the "International Classification of Functioning" is likely to provide a greater influence on falls reduction. "PDSAFE" is a multi-dimensional, physiotherapist delivered, individually tailored, progressive, home-based programme. It is designed with a strong evidence-based approach and illustrates a model for the clinical delivery of the conceptual theory discussed. Implications for Rehabilitation Parkinson's disease demonstrates a spectrum of motor and non-motor symptoms, where falling is common and disabling. Current medical and surgical management have minimal impact on falls, rehabilitation of falls risk factors has strong evidence but the most appropriate intervention to reduce overall fall rate remains inconclusive. Addressing all components of the International Classification of Function in a multifactorial model when designing falls rehabilitation interventions may be more effective at reducing fall rates in people with Parkinson's than treating isolated risk factors. The clinical model for falls rehabilitation in people with Parkinson's should be multi-dimensional.status: publishe