National Climate Policies: Aiming at the Factor 4 Target by 2050?

International Nuclear Information System (INIS)

Godard, Olivier

2016-01-01

The paper considers how the governments of midsize developed countries could define national strategies to control greenhouse gas emissions, assuming that such strategies are the product of cognitive and ethical choices relating to global climate scenarios and the rule for allocating shares of expected global climate damage to individual States. After evaluating the carbon value linked to each cognitive-ethical configuration, I identify the configurations that justify the target of dividing national emissions by 4 between 1990 and 2050 - a goal known as 'Factor 4'. Lastly, I examine the resulting constraints on the shape of the control trajectory leading to that target

Catching moving targets: cancer stem cell hierarchies, therapy-resistance & considerations for clinical intervention.

LENUS (Irish Health Repository)

Gasch, Claudia

2017-01-01

It is widely believed that targeting the tumour-initiating cancer stem cell (CSC) component of malignancy has great therapeutic potential, particularly in therapy-resistant disease. However, despite concerted efforts, CSC-targeting strategies have not been efficiently translated to the clinic. This is partly due to our incomplete understanding of the mechanisms underlying CSC therapy-resistance. In particular, the relationship between therapy-resistance and the organisation of CSCs as Stem-Progenitor-Differentiated cell hierarchies has not been widely studied. In this review we argue that modern clinical strategies should appreciate that the CSC hierarchy is a dynamic target that contains sensitive and resistant components and expresses a collection of therapy-resisting mechanisms. We propose that the CSC hierarchy at primary presentation changes in response to clinical intervention, resulting in a recurrent malignancy that should be targeted differently. As such, addressing the hierarchical organisation of CSCs into our bench-side theory should expedite translation of CSC-targeting to bed-side practice. In conclusion, we discuss strategies through which we can catch these moving clinical targets to specifically compromise therapy-resistant disease.

Imbalanced target prediction with pattern discovery on clinical data repositories.

Science.gov (United States)

Chan, Tak-Ming; Li, Yuxi; Chiau, Choo-Chiap; Zhu, Jane; Jiang, Jie; Huo, Yong

2017-04-20

Clinical data repositories (CDR) have great potential to improve outcome prediction and risk modeling. However, most clinical studies require careful study design, dedicated data collection efforts, and sophisticated modeling techniques before a hypothesis can be tested. We aim to bridge this gap, so that clinical domain users can perform first-hand prediction on existing repository data without complicated handling, and obtain insightful patterns of imbalanced targets for a formal study before it is conducted. We specifically target for interpretability for domain users where the model can be conveniently explained and applied in clinical practice. We propose an interpretable pattern model which is noise (missing) tolerant for practice data. To address the challenge of imbalanced targets of interest in clinical research, e.g., deaths less than a few percent, the geometric mean of sensitivity and specificity (G-mean) optimization criterion is employed, with which a simple but effective heuristic algorithm is developed. We compared pattern discovery to clinically interpretable methods on two retrospective clinical datasets. They contain 14.9% deaths in 1 year in the thoracic dataset and 9.1% deaths in the cardiac dataset, respectively. In spite of the imbalance challenge shown on other methods, pattern discovery consistently shows competitive cross-validated prediction performance. Compared to logistic regression, Naïve Bayes, and decision tree, pattern discovery achieves statistically significant (p-values repositories with imbalance and noise. The prediction results and interpretable patterns can provide insights in an agile and inexpensive way for the potential formal studies.

Impact of the national targeted Hepatitis A immunisation program in Australia: 2000-2014.

Science.gov (United States)

Thompson, Craig; Dey, Aditi; Fearnley, Emily; Polkinghorne, Benjamin; Beard, Frank

2017-01-03

In November 2005, hepatitis A vaccine was funded under the Australian National Immunisation Program for Aboriginal and Torres Strait Islander (Indigenous) children aged 12-24months in the targeted jurisdictions of Queensland, South Australia, Western Australia and the Northern Territory. We reviewed the epidemiology of hepatitis A from 2000 to 2014 using data from the Australian National Notifiable Diseases Surveillance System, the National Hospital Morbidity Database, and Australian Bureau of Statistics causes-of-death data. The impact of the national hepatitis A immunisation program was assessed by comparison of pre-vaccine (2000-2005) and post-vaccine time periods (2006-2014), by age group, Indigenous status and jurisdiction using incidence rate ratios (IRR) per 100,000 population and 95% confidence intervals (CI). The national pre-vaccine notification rate in Indigenous people was four times higher than the non-Indigenous rate, and declined from 8.41 per 100,000 (95% CI 5.03-11.79) pre-vaccine to 0.85 per 100,000 (95% CI 0.00-1.99) post-vaccine, becoming similar to the non-Indigenous rate. Notification and hospitalisation rates in Indigenous children aged <5years from targeted jurisdictions declined in the post-vaccine period when compared to the pre-vaccine period (notifications: IRR=0.07; 95% CI 0.04-0.13; hospitalisations: IRR=0.04; 95% CI 0.01-0.16). As did notification rates in Indigenous people aged 5-19 (IRR=0.08; 95% CI 0.05-0.13) and 20-49years (IRR=0.06; 95% CI 0.02-0.15) in targeted jurisdictions. For non-Indigenous people from targeted jurisdictions, notification rates decreased significantly in children aged <5years (IRR 0.47; 95% CI 0.31-0.71), and significantly more overall (IRR=0.43; 95% CI 0.39-0.47) compared to non-Indigenous people from non-targeted jurisdictions (IRR=0.60; 95% CI 0.56-0.64). The national hepatitis A immunisation program has had a significant impact in the targeted population with relatively modest vaccine coverage, with

Clinical trials in hospitalized heart failure patients: targeting interventions to optimal phenotypic subpopulations.

Science.gov (United States)

Vaduganathan, Muthiah; Butler, Javed; Roessig, Lothar; Fonarow, Gregg C; Greene, Stephen J; Metra, Marco; Cotter, Gadi; Kupfer, Stuart; Zalewski, Andrew; Sato, Naoki; Filippatos, Gerasimos; Gheorghiade, Mihai

2015-07-01

With one possible exception, the last decade of clinical trials in hospitalized heart failure (HHF) patients has failed to demonstrate improvement in long-term clinical outcomes. This trend necessitates a need to evaluate optimal drug development strategies and standards of trial conduct. It has become increasingly important to recognize the heterogeneity among HHF patients and the differential characterization of novel drug candidates. Targeting these agents to specific subpopulations may afford optimal net response related to the particular mode of action of the drug. Analyses of previous trials demonstrate profound differences in the baseline characteristics of patients enrolled across global regions and participating sites. Such differences may influence risks for events and interpretation of results. Therefore, the actual execution of trials and the epidemiology of HHF populations at the investigative sites must be taken into consideration. Collaboration among participating sites including the provision of registry data tailored to the planned development program will optimize trial conduct. Observational data prior to study initiation may enable sites to feedback and engage in protocol development to allow for feasible and valid clinical trial conduct. This site-centered, epidemiology-based network environment may facilitate studies in specific patient populations and promote optimal data collection and clear interpretation of drug safety and efficacy. This review summarizes the roundtable discussion held by a multidisciplinary team of representatives from academia, National Institutes of Health, industry, regulatory agencies, payers, and contract and academic research organizations to answer the question: Who should be targeted for novel therapies in HHF?

Identification of clinical target areas in the brainstem of prion‐infected mice

Science.gov (United States)

Mirabile, Ilaria; Jat, Parmjit S.; Brandner, Sebastian

2015-01-01

Aims While prion infection ultimately involves the entire brain, it has long been thought that the abrupt clinical onset and rapid neurological decline in laboratory rodents relates to involvement of specific critical neuroanatomical target areas. The severity and type of clinical signs, together with the rapid progression, suggest the brainstem as a candidate location for such critical areas. In this study we aimed to correlate prion pathology with clinical phenotype in order to identify clinical target areas. Method We conducted a comprehensive survey of brainstem pathology in mice infected with two distinct prion strains, which produce different patterns of pathology, in mice overexpressing prion protein (with accelerated clinical onset) and in mice in which neuronal expression was reduced by gene targeting (which greatly delays clinical onset). Results We identified specific brainstem areas that are affected by prion pathology during the progression of the disease. In the early phase of disease the locus coeruleus, the nucleus of the solitary tract, and the pre‐Bötzinger complex were affected by prion protein deposition. This was followed by involvement of the motor and autonomic centres of the brainstem. Conclusions Neurodegeneration in the locus coeruleus, the nucleus of the solitary tract and the pre‐Bötzinger complex predominated and corresponded to the manifestation of the clinical phenotype. Because of their fundamental role in controlling autonomic function and the overlap with clinical signs in sporadic Creutzfeldt–Jakob disease, we suggest that these nuclei represent key clinical target areas in prion diseases. PMID:25311251

Clinically targeted screening for congenital CMV - potential for integration into the National Hearing Screening Programme.

Science.gov (United States)

Kadambari, S; Luck, S; Davis, A; Williams, Ej; Berrington, J; Griffiths, Pd; Sharland, M

2013-10-01

Screening for a condition should only be undertaken if certain strict criteria are met. Congenital CMV (cCMV) is a leading cause of sensorineuronal hearing loss (SNHL) and meets many of these criteria, but is not currently screened for in the UK. Ganciclovir reduces CMV-induced progressive SNHL if treatment is begun in the first month of life. The Newborn Hearing Screening Programme (NHSP) has been shown to identify SNHL at the earliest possible age. The potential of integrating screening for cCMV into the NHSP is discussed to consolidate the link between screening, early diagnosis and management. The early diagnosis and treatment of cCMV may prevent a small proportion of late SNHL. In the absence of any screening programme, we provide evidence that clinically targeted screening through the NHSP is a potential option in the UK, enhancing the diagnostic pathway and enabling appropriate early treatment to reduce long-term morbidity. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

An Overview of the Target Fabrication Operations at Lawrence Livermore National Laboratory

International Nuclear Information System (INIS)

Hibbard, R L; Bono, M J

2005-01-01

The Target Engineering team at Lawrence Livermore National Laboratory (LLNL) builds precision laser targets for the National Ignition Facility (NIF) and the Omega Laser in Rochester, NY, and other experimental facilities. The physics requirements demand precision in these targets, which creates a constant need for innovative manufacturing processes. As experimental diagnostics improve, there is greater demand for precision in fabrication, assembly, metrology, and documentation of as-built targets. The team specializes in meso-scale fabrication with core competencies in diamond turning, assembly, and metrology. Figure 1 shows a typical diamond turning center. The team builds over 200 laser targets per year in batches of five to fifteen targets. Thus, all are small-lot custom builds, and most are novel designs requiring engineering and process development. Component materials are metals, polymers and low density aerogel foams. Custom fixturing is used to locate parts on the Diamond Turning Machines (DTM) and assembly stations. This ensures parts can be repeatably located during manufacturing operations. Most target builds involve a series of fabricating one surface with features and then relocating the components on another fixture to finish the opposite side of the component. These components are then assembled to complete multiple-component targets. These targets are typically built one at a time. Cost and efficiency are issues with production of targets, and the team is developing batch processing techniques to meet precision target specifications and cost goals. Three example target builds will highlight some of the fabrication and material issues faced at LLNL. A low temperature Rayleigh Taylor target shows how multiple precision targets can be fabricated out of a single large disk. The ignition double shell targets highlight the required manufacturing complexity. A low density aerogel target highlights some material handling and assembly issues. The metrology

Hydrodynamic instabilities in beryllium targets for the National Ignition Facility

Energy Technology Data Exchange (ETDEWEB)

Yi, S. A., E-mail: austinyi@lanl.gov; Simakov, A. N.; Wilson, D. C.; Olson, R. E.; Kline, J. L.; Batha, S. H. [Los Alamos National Laboratory, P.O. Box 1663, Los Alamos, New Mexico 87545 (United States); Clark, D. S.; Hammel, B. A.; Milovich, J. L.; Salmonson, J. D.; Kozioziemski, B. J. [Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, California 94551 (United States)

2014-09-15

Beryllium ablators offer higher ablation velocity, rate, and pressure than their carbon-based counterparts, with the potential to increase the probability of achieving ignition at the National Ignition Facility (NIF) [E. I. Moses et al., Phys. Plasmas 16, 041006 (2009)]. We present here a detailed hydrodynamic stability analysis of low (NIF Revision 6.1) and high adiabat NIF beryllium target designs. Our targets are optimized to fully utilize the advantages of beryllium in order to suppress the growth of hydrodynamic instabilities. This results in an implosion that resists breakup of the capsule, and simultaneously minimizes the amount of ablator material mixed into the fuel. We quantify the improvement in stability of beryllium targets relative to plastic ones, and show that a low adiabat beryllium capsule can be at least as stable at the ablation front as a high adiabat plastic target.

7 CFR 3402.4 - Food and agricultural sciences areas targeted for National Needs Graduate and Postdoctoral...

Science.gov (United States)

2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Food and agricultural sciences areas targeted for..., AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE FOOD AND AGRICULTURAL SCIENCES NATIONAL NEEDS... sciences areas targeted for National Needs Graduate and Postdoctoral Fellowship Grants Program support...

A combination of process of care and clinical target among type 2 diabetes mellitus patients in general medical clinics and specialist diabetes clinics at hospital levels.

Science.gov (United States)

Sieng, Sokha; Hurst, Cameron

2017-08-07

This study compares a combination of processes of care and clinical targets among patients with type 2 diabetes mellitus (T2DM) between specialist diabetes clinics (SDCs) and general medical clinics (GMCs), and how differences between these two types of clinics differ with hospital type (community, provincial and regional). Type 2 diabetes mellitus patient medical records were collected from 595 hospitals (499 community, 70 provincial, 26 regional) in Thailand between April 1 to June 30, 2012 resulting in a cross-sectional sample of 26,860 patients. Generalized linear mixed modeling was conducted to examine associations between clinic type and quality of care. The outcome variables of interest were split into clinical targets and process of care. A subsequent subgroup analysis was conducted to examine if the nature of clinical target and process of care differences between GMCs and SDCs varied with hospital type (regional, provincial, community). Regardless of the types of hospitals (regional, provincial, or community) patients attending SDCs were considerably more likely to have eye and foot exam. In terms of larger hospitals (regional and provincial) patients attending SDCs were more likely to achieve HbA1c exam, All FACE exam, BP target, and the Num7Q. Interestingly, SDCs performed better than GMCs at only provincial hospitals for LDL-C target and the All7Q. Finally, patients with T2DM who attended community hospital-GMCs had a better chance of achieving the blood pressure target than patients who attended community hospital-SDCs. Specialized diabetes clinics outperform general medical clinics for both regional and provincial hospitals for all quality of care indicators and the number of quality of care indicators achieved was never lower. However, this better performance of SDC was not observed in community hospital. Indeed, GMCs outperformed SDCs for some quality of care indicators in the community level setting.

Inertial confinement fusion target insertion concepts for the National Ignition Facility

International Nuclear Information System (INIS)

Laughon, G.J.; Schultz, K.R.

1996-01-01

The National Ignition Facility (NIF) will be used to demonstrate fusion ignition in a laboratory environment in order to support development of inertial fusion as a potential fusion energy source for civilian use. However, target insertion must first be addressed before inertial fusion can become a practical energy source. Since target insertion systems currently utilized are not suitable for multiple shots in quick succession, insertion concepts involving free-falling and artificially accelerated targets are developed and evaluated against a set of predetermined guidelines. It is shown that a system involving a fast retraction positioner would be suitable. 5 refs., 4 figs

National Ignition Facility Cryogenic Target Systems Interim Management Plan

International Nuclear Information System (INIS)

Warner, B

2002-01-01

Restricted availability of funding has had an adverse impact, unforeseen at the time of the original decision to projectize the National Ignition Facility (NIF) Cryogenic Target Handling Systems (NCTS) Program, on the planning and initiation of these efforts. The purpose of this document is to provide an interim project management plan describing the organizational structure and management processes currently in place for NCTS. Preparation of a Program Execution Plan (PEP) for NCTS has been initiated, and a current draft is provided as Attachment 1 to this document. The National Ignition Facility is a multi-megajoule laser facility being constructed at Lawrence Livermore National Laboratory (LLNL) by the National Nuclear Security Administration (NNSA) in the Department of Energy (DOE). Its primary mission is to support the Stockpile Stewardship Program (SSP) by performing experiments studying weapons physics, including fusion ignition. NIF also supports the missions of weapons effects, inertial fusion energy, and basic science in high-energy-density physics. NIF will be operated by LLNL under contract to the University of California (UC) as a national user facility. NIF is a low-hazard, radiological facility, and its operation will meet all applicable federal, state, and local Environmental Safety and Health (ES and H) requirements. The NCTS Interim Management Plan provides a summary of primary design criteria and functional requirements, current organizational structure, tracking and reporting procedures, and current planning estimates of project scope, cost, and schedule. The NIF Director controls the NIF Cryogenic Target Systems Interim Management Plan. Overall scope content and execution schedules for the High Energy Density Physics Campaign (SSP Campaign 10) are currently undergoing rebaselining and will be brought into alignment with resources expected to be available throughout the NNSA Future Years National Security Plan (FYNSP). The revised schedule for

Design of the target area for the National Ignition Facility

International Nuclear Information System (INIS)

Foley, R.J.; Karpenko, V.P.; Adams, C.H.

1997-01-01

The preliminary design of the target area for the National Ignition Facility has been completed. The target area is required to meet a challenging set of engineering system design requirements and user needs. The target area must provide the appropriate conditions before, during, and after each shot. The repeated introduction of large amounts of laser energy into the chamber and subsequent target emissions represent new design challenges for ICF facility design. Prior to each shot, the target area must provide the required target illumination, target chamber vacuum, diagnostics, and optically stable structures. During the shot, the impact of the target emissions on the target chamber, diagnostics, and optical elements is minimized and the workers and public are protected from excessive prompt radiation doses. After the shot, residual radioactivation is managed to allow the required accessibility. Diagnostic data is retrieved, operations and maintenance activities are conducted, and the facility is ready for the next shot. The target area subsystems include the target chamber, target positioner, structural systems, target diagnostics, environmental systems, and the final optics assembly. The engineering design of the major elements of the target area requires a unique combination of precision engineering, structural analysis, opto-mechanical design, random vibration suppression, thermal stability, materials engineering, robotics, and optical cleanliness. The facility has been designed to conduct both x- ray driven targets and to be converted at a later date for direct drive experiments. The NIF has been configured to provide a wide range of experimental environments for the anticipated user groups of the facility. The design status of the major elements of the target area is described

Quality of clinical trials: A moving target

Science.gov (United States)

Bhatt, Arun

2011-01-01

Quality of clinical trials depends on data integrity and subject protection. Globalization, outsourcing and increasing complexicity of clinical trials have made the target of achieving global quality challenging. The quality, as judged by regulatory inspections of the investigator sites, sponsors/contract research organizations and Institutional Review Board, has been of concern to the US Food and Drug Administration, as there has been hardly any change in frequency and nature of common deficiencies. To meet the regulatory expectations, the sponsors need to improve quality by developing systems with specific standards for each clinical trial process. The quality systems include: personnel roles and responsibilities, training, policies and procedures, quality assurance and auditing, document management, record retention, and reporting and corrective and preventive action. With an objective to improve quality, the FDA has planned new inspection approaches such as risk-based inspections, surveillance inspections, real-time oversight, and audit of sponsor quality systems. The FDA has partnered with Duke University for Clinical Trials Transformation Initiative, which will conduct research projects on design principles, data quality and quantity including monitoring, study start-up, and adverse event reporting. These recent initiatives will go a long way in improving quality of clinical trials. PMID:22145122

Recent developments in the target facilities at Argonne National Laboratory

International Nuclear Information System (INIS)

Greene, J.P.; Thomas, G.E.

1989-01-01

A description is given of recent developments in the target facility at Argonne National Laboratory (ANL). Highlights include equipment upgrades which enable us to provide enhanced capabilities for support of the Argonne Heavy-Ion ATLAS Accelerator Project. Also, future plans and additional equipment acquisitions will be discussed. (orig.)

Impacts of National Decarbonization Targets for Subnational Societal Priorities

Science.gov (United States)

Peng, W.; Iyer, G.

2017-12-01

Carbon mitigation has well-recognized linkages with other environmental and socioeconomic priorities, such as air pollution, economic development, employment, etc. While climate change is a global issue, many other societal priorities are local concerns. Since local efforts form the pillars of achieving co-benefits and avoiding dis-benefits at the national level, it is critical to go beyond national-level analyses and focus on the synergies and tradeoffs at the subnational level. Here we use the United States as an example to evaluate the impacts of mid-century national-level deep decarbonization target for state-level societal priorities. Based on the Global Change Assessment Model with state-level details for the US (GCAM-USA), we design two mid-century scenarios: A Reference scenario that assumes the U.S. undertakes no additional climate mitigation policy, and a Deep Decarbonization Scenario that assumes the U.S. achieves the NDC goal through 2025 (26-28% reduction relative to 2005 levels) and then follows a straight-line trajectory to 80% reductions in economy-wide GHG emissions by 2050 relative to 2005. We then compare these two scenarios for a variety of metrics of carbon mitigation and other societal priorities in 2050. We highlight two findings. First, the synergies and tradeoffs of carbon mitigation with other societal goals at the subnational level can be quite different from the national level. For example, while deep decarbonization could improve national energy security by reducing the overall dependence on energy imports, it may exacerbate energy independence goals for some states by increasing inter-state electricity imports. Second, achieving national-level decarbonization target could result in unequal regional impacts across states. We find uneven geographic impacts for air pollution (more co-reductions occur in the eastern states), economic costs (energy prices increase more in the northeastern states) and employment (jobs increase in the western

Recent developments in the target facilities at Argonne National Laboratory

International Nuclear Information System (INIS)

Greene, J.P.; Thomas, G.E.

1988-01-01

A description is given of recent developments in the target facility at Argonne National Laboratory. Highlights include equipment upgrades which enables us to provide enhanced capabilities for support of the Argonne Heavy-Ion ATLAS Accelerator Project. Also future plans and additional equipment acquisitions will be discussed. 3 refs., 3 tabs

Los Alamos contribution to target diagnostics on the National Ignition Facility

Energy Technology Data Exchange (ETDEWEB)

Mack, J.M.; Baker, D.A.; Caldwell, S.E. [and others

1994-07-01

The National Ignition Facility (NIF) will have a large suite of sophisticated target diagnostics. This will allow thoroughly diagnosed experiments to be performed both at the ignition and pre-ignition levels. As part of the national effort Los Alamos National Laboratory will design, construct and implement a number of diagnostics for the NIF. This paper describes Los Alamos contributions to the ``phase I diagnostics.`` Phase I represents the most fundamental and basic measurement systems that will form the core for most work on the NIF. The Los Alamos effort falls into four categories: moderate to hard X-ray (time resolved imaging neutron spectroscopy- primarily with neutron time of flight devices; burn diagnostics utilizing gamma ray measurements; testing measurement concepts on the TRIDENT laser system at Los Alamos. Because of the high blast, debris and radiation environment, the design of high resolution X-ray imaging systems present significant challenges. Systems with close target proximity require special protection and methods for such protection is described. The system design specifications based on expected target performance parameters is also described. Diagnosis of nuclear yield and burn will be crucial to the NIF operation. Nuclear reaction diagnosis utilizing both neutron and gamma ray detection is discussed. The Los Alamos TRIDENT laser system will be used extensively for the development of new measurement concepts and diagnostic instrumentation. Some its potential roles in the development of diagnostics for NIF are given.

Los Alamos contribution to target diagnostics on the National Ignition Facility

International Nuclear Information System (INIS)

Mack, J.M.; Baker, D.A.; Caldwell, S.E.

1994-01-01

The National Ignition Facility (NIF) will have a large suite of sophisticated target diagnostics. This will allow thoroughly diagnosed experiments to be performed both at the ignition and pre-ignition levels. As part of the national effort Los Alamos National Laboratory will design, construct and implement a number of diagnostics for the NIF. This paper describes Los Alamos contributions to the ''phase I diagnostics.'' Phase I represents the most fundamental and basic measurement systems that will form the core for most work on the NIF. The Los Alamos effort falls into four categories: moderate to hard X-ray (time resolved imaging neutron spectroscopy- primarily with neutron time of flight devices; burn diagnostics utilizing gamma ray measurements; testing measurement concepts on the TRIDENT laser system at Los Alamos. Because of the high blast, debris and radiation environment, the design of high resolution X-ray imaging systems present significant challenges. Systems with close target proximity require special protection and methods for such protection is described. The system design specifications based on expected target performance parameters is also described. Diagnosis of nuclear yield and burn will be crucial to the NIF operation. Nuclear reaction diagnosis utilizing both neutron and gamma ray detection is discussed. The Los Alamos TRIDENT laser system will be used extensively for the development of new measurement concepts and diagnostic instrumentation. Some its potential roles in the development of diagnostics for NIF are given

Target diagnostic system for the National Ignition Facility (NIF)

International Nuclear Information System (INIS)

Leeper, R.J.; Chandler, G.A.; Cooper, G.W.; Derzon, M.S.

1996-01-01

A review of recent progress on the design of a diagnostic system proposed for ignition target experiments on the National Ignition Facility (NIF) will be presented. This diagnostic package contains an extensive suite of optical, x-ray, gamma-ray, and neutron diagnostics that enable measurements of the performance of both direct and indirect driven NIF targets. The philosophy used in designing all of the diagnostics in the set has emphasized redundant and independent measurement of fundamental physical quantities relevant to the operation of the NIF target. A unique feature of these diagnostics is that they are being designed to be capable of operating, in the high radiation, EMP, and debris backgrounds expected on the NIF facility. The diagnostic system proposed can be categorized into three broad areas: laser characterization, hohlraum characterization, and capsule performance diagnostics. The operating principles of a representative instrument from each class of diagnostic employed in this package will be summarized and illustrated with data obtained in recent prototype diagnostic tests

National responses to global health targets: exploring policy transfer in the context of the UNAIDS '90-90-90' treatment targets in Ghana and Uganda.

Science.gov (United States)

McRobie, Ellen; Matovu, Fred; Nanyiti, Aisha; Nonvignon, Justice; Abankwah, Daniel Nana Yaw; Case, Kelsey K; Hallett, Timothy B; Hanefeld, Johanna; Conteh, Lesong

2018-01-01

Global health organizations frequently set disease-specific targets with the goal of eliciting adoption at the national-level; consideration of the influence of target setting on national policies, programme and health budgets is of benefit to those setting targets and those intended to respond. In 2014, the Joint United Nations Programme on HIV/AIDS set 'ambitious' treatment targets for country adoption: 90% of HIV-positive persons should know their status; 90% of those on treatment; 90% of those achieving viral suppression. Using case studies from Ghana and Uganda, we explore how the target and its associated policy content have been adopted at the national level. That is whether adoption is in rhetoric only or supported by programme, policy or budgetary changes. We review 23 (14 from Ghana, 9 from Uganda) national policy, operational and strategic documents for the HIV response and assess commitments to '90-90-90'. In-person semi-structured interviews were conducted with purposively sampled key informants (17 in Ghana, 20 in Uganda) involved in programme-planning and resource allocation within HIV to gain insight into factors facilitating adoption of 90-90-90. Interviews were transcribed and analysed thematically, inductively and deductively, guided by pre-existing policy theories, including Dolowitz and Marsh's policy transfer framework to describe features of the transfer and the Global Health Advocacy and Policy Project framework to explain observations. Regardless of notable resource constraints, transfer of the 90-90-90 targets was evident beyond rhetoric with substantial shifts in policy and programme activities. In both countries, there was evidence of attempts to minimize resource constraints by seeking programme efficiencies, prioritization of programme activities and devising domestic financing mechanisms; however, significant resource gaps persist. An effective health network, comprised of global and local actors, mediated the adoption and adaptation

Quality of clinical trials: A moving target

Directory of Open Access Journals (Sweden)

Arun Bhatt

2011-01-01

Full Text Available Quality of clinical trials depends on data integrity and subject protection. Globalization, outsourcing and increasing complexicity of clinical trials have made the target of achieving global quality challenging. The quality, as judged by regulatory inspections of the investigator sites, sponsors/contract research organizations and Institutional Review Board, has been of concern to the US Food and Drug Administration, as there has been hardly any change in frequency and nature of common deficiencies. To meet the regulatory expectations, the sponsors need to improve quality by developing systems with specific standards for each clinical trial process. The quality systems include: personnel roles and responsibilities, training, policies and procedures, quality assurance and auditing, document management, record retention, and reporting and corrective and preventive action. With an objective to improve quality, the FDA has planned new inspection approaches such as risk-based inspections, surveillance inspections, real-time oversight, and audit of sponsor quality systems. The FDA has partnered with Duke University for Clinical Trials Transformation Initiative, which will conduct research projects on design principles, data quality and quantity including monitoring, study start-up, and adverse event reporting. These recent initiatives will go a long way in improving quality of clinical trials.

Statistical inference on censored data for targeted clinical trials under enrichment design.

Science.gov (United States)

Chen, Chen-Fang; Lin, Jr-Rung; Liu, Jen-Pei

2013-01-01

For the traditional clinical trials, inclusion and exclusion criteria are usually based on some clinical endpoints; the genetic or genomic variability of the trial participants are not totally utilized in the criteria. After completion of the human genome project, the disease targets at the molecular level can be identified and can be utilized for the treatment of diseases. However, the accuracy of diagnostic devices for identification of such molecular targets is usually not perfect. Some of the patients enrolled in targeted clinical trials with a positive result for the molecular target might not have the specific molecular targets. As a result, the treatment effect may be underestimated in the patient population truly with the molecular target. To resolve this issue, under the exponential distribution, we develop inferential procedures for the treatment effects of the targeted drug based on the censored endpoints in the patients truly with the molecular targets. Under an enrichment design, we propose using the expectation-maximization algorithm in conjunction with the bootstrap technique to incorporate the inaccuracy of the diagnostic device for detection of the molecular targets on the inference of the treatment effects. A simulation study was conducted to empirically investigate the performance of the proposed methods. Simulation results demonstrate that under the exponential distribution, the proposed estimator is nearly unbiased with adequate precision, and the confidence interval can provide adequate coverage probability. In addition, the proposed testing procedure can adequately control the size with sufficient power. On the other hand, when the proportional hazard assumption is violated, additional simulation studies show that the type I error rate is not controlled at the nominal level and is an increasing function of the positive predictive value. A numerical example illustrates the proposed procedures. Copyright © 2013 John Wiley & Sons, Ltd.

Perception survey on the introduction of clinical performance examination as part of the national nursing licensing examination in Korea

Directory of Open Access Journals (Sweden)

Su Jin Shin

2017-10-01

Full Text Available Purpose The purpose of this study was to analyze opinions about the action plan for implementation of clinical performance exam as part of the national nursing licensing examination and presents the expected effects of the performance exam and aspects to consider regarding its implementation. Methods This study used a mixed-methods design. Quantitative data were collected by a questionnaire survey, while qualitative data were collected by focus group interviews with experts. The survey targeted 200 nursing professors and clinical nurses with more than 5 years of work experience, and the focus group interviews were conducted with 28 of professors, clinical instructors, and nurses at hospitals. Results First, nursing professors and clinical specialists agreed that the current written tests have limitations in evaluating examinees’ ability, and that the introduction of a clinical performance exam will yield positive results. Clinical performance exam is necessary to evaluate and improve nurses’ work ability, which means that the implementation of a performance exam is advisable if its credibility and validity can be verified. Second, most respondents chose direct performance exams using simulators or standardized patients as the most suitable format of the test. Conclusion In conclusion, the current national nursing licensing exam is somewhat limited in its ability to identify competent nurses. Thus, the time has come for us to seriously consider the introduction of a performance exam. The prerequisites for successfully implementing clinical performance exam as part of the national nursing licensing exam are a professional training process and forming a consortium to standardize practical training.

Enhanced clinical pharmacy service targeting tools: risk-predictive algorithms.

Science.gov (United States)

El Hajji, Feras W D; Scullin, Claire; Scott, Michael G; McElnay, James C

2015-04-01

This study aimed to determine the value of using a mix of clinical pharmacy data and routine hospital admission spell data in the development of predictive algorithms. Exploration of risk factors in hospitalized patients, together with the targeting strategies devised, will enable the prioritization of clinical pharmacy services to optimize patient outcomes. Predictive algorithms were developed using a number of detailed steps using a 75% sample of integrated medicines management (IMM) patients, and validated using the remaining 25%. IMM patients receive targeted clinical pharmacy input throughout their hospital stay. The algorithms were applied to the validation sample, and predicted risk probability was generated for each patient from the coefficients. Risk threshold for the algorithms were determined by identifying the cut-off points of risk scores at which the algorithm would have the highest discriminative performance. Clinical pharmacy staffing levels were obtained from the pharmacy department staffing database. Numbers of previous emergency admissions and admission medicines together with age-adjusted co-morbidity and diuretic receipt formed a 12-month post-discharge and/or readmission risk algorithm. Age-adjusted co-morbidity proved to be the best index to predict mortality. Increased numbers of clinical pharmacy staff at ward level was correlated with a reduction in risk-adjusted mortality index (RAMI). Algorithms created were valid in predicting risk of in-hospital and post-discharge mortality and risk of hospital readmission 3, 6 and 12 months post-discharge. The provision of ward-based clinical pharmacy services is a key component to reducing RAMI and enabling the full benefits of pharmacy input to patient care to be realized. © 2014 John Wiley & Sons, Ltd.

Target experimental area and systems of the Us national ignition facility

International Nuclear Information System (INIS)

Tobin, M.; Van Wonterghem, B.; MacGowan, B.J.; Hibbard, W.; Kalantar, D.; Lee, F.D.; Pittenger, L.; Wong, K.

2000-01-01

One of the major goals of the US National Ignition Facility is the demonstration of laser driven fusion ignition and burn of targets by inertial confinement and provide capability for a wide variety of high energy density physics experiments. The NIF target area houses the optical systems required to focus the 192 beamlets to a target precisely positioned at the center of the 10 meter diameter, 10-cm thick aluminum target chamber. The chamber serves as mounting surface for the 48 final optics assemblies, the target alignment and positioning equipment, and the target diagnostics. The internal surfaces of the chamber are protected by louvered steel beam dumps. The target area also provides the necessary shielding against target emission and environmental protection equipment. Despite its complexity, the design provides the flexibility to accommodate the needs of the various NIF user groups, such as direct and indirect drive irradiation geometries, modular final optics design, capability to handle cryogenic targets, and easily re-configurable diagnostic instruments. Efficient target area operations are ensured by using line-replaceable designs for systems requiring frequent inspection, maintenance and reconfiguration, such as the final optics, debris shields, phase plates and the diagnostic instruments. A precision diagnostic instrument manipulator (DIMS) allows fast removal and precise repositioning of diagnostic instruments. In addition we will describe several activities to enhance the target chamber availability, such as the target debris mitigation, the use of standard experimental configurations and the development of smart shot operations planning tools. (authors)

Bayesian Nonparametric Estimation of Targeted Agent Effects on Biomarker Change to Predict Clinical Outcome

Science.gov (United States)

Graziani, Rebecca; Guindani, Michele; Thall, Peter F.

2015-01-01

Summary The effect of a targeted agent on a cancer patient's clinical outcome putatively is mediated through the agent's effect on one or more early biological events. This is motivated by pre-clinical experiments with cells or animals that identify such events, represented by binary or quantitative biomarkers. When evaluating targeted agents in humans, central questions are whether the distribution of a targeted biomarker changes following treatment, the nature and magnitude of this change, and whether it is associated with clinical outcome. Major difficulties in estimating these effects are that a biomarker's distribution may be complex, vary substantially between patients, and have complicated relationships with clinical outcomes. We present a probabilistically coherent framework for modeling and estimation in this setting, including a hierarchical Bayesian nonparametric mixture model for biomarkers that we use to define a functional profile of pre-versus-post treatment biomarker distribution change. The functional is similar to the receiver operating characteristic used in diagnostic testing. The hierarchical model yields clusters of individual patient biomarker profile functionals, and we use the profile as a covariate in a regression model for clinical outcome. The methodology is illustrated by analysis of a dataset from a clinical trial in prostate cancer using imatinib to target platelet-derived growth factor, with the clinical aim to improve progression-free survival time. PMID:25319212

Clinical proteomics-driven precision medicine for targeted cancer therapy: current overview and future perspectives.

Science.gov (United States)

Zhou, Li; Wang, Kui; Li, Qifu; Nice, Edouard C; Zhang, Haiyuan; Huang, Canhua

2016-01-01

Cancer is a common disease that is a leading cause of death worldwide. Currently, early detection and novel therapeutic strategies are urgently needed for more effective management of cancer. Importantly, protein profiling using clinical proteomic strategies, with spectacular sensitivity and precision, offer excellent promise for the identification of potential biomarkers that would direct the development of targeted therapeutic anticancer drugs for precision medicine. In particular, clinical sample sources, including tumor tissues and body fluids (blood, feces, urine and saliva), have been widely investigated using modern high-throughput mass spectrometry-based proteomic approaches combined with bioinformatic analysis, to pursue the possibilities of precision medicine for targeted cancer therapy. Discussed in this review are the current advantages and limitations of clinical proteomics, the available strategies of clinical proteomics for the management of precision medicine, as well as the challenges and future perspectives of clinical proteomics-driven precision medicine for targeted cancer therapy.

Clinical target volume for rectal cancer. Preoperative radiotherapy

International Nuclear Information System (INIS)

Lorchel, F.; Bossel, J.F.; Baron, M.H.; Goubard, O.; Bartholomot, B.; Mantion, G.; Pelissier, E.P.; Maingon, P.

2001-01-01

The total meso-rectal excision allows the marked increase of the local control rate in rectal cancer. Therefore, the meso-rectal space is the usual field for the spread of rectal cancer cells. It could therefore be considered as the clinical target volume in the preoperative plan by the radiation oncologist. We propose to identify the mesorectum on anatomical structures of a treatment-position CT scan. (authors)

SU-F-J-160: Clinical Evaluation of Targeting Accuracy in Radiosurgery Using Tractography

Energy Technology Data Exchange (ETDEWEB)

Juh, R; Han, J; Kim, C; Oh, C [Seoul National University Bundang Hospital, Seongnamsi, GyeonggiDo (Korea, Republic of); Suh, T [The catholic university of Korea, Seoul (Korea, Republic of)

2016-06-15

Purpose: Focal radiosurgery is a common treatment modality for trigeminal neuralgia (TN), a neuropathic facial pain condition. Assessment of treatment effectiveness is primarily clinical, given the paucity of investigational tools to assess trigeminal nerve changes. The efficiency of radiosurgery is related to its highly precise targeting. We assessed clinically the targeting accuracy of radiosurgery with Gamma knife. We hypothesized that trigeminal tractography provides more information than 2D-MR imaging, allowing detection of unique, focal changes in the target area after radiosurgery. Methods: Sixteen TN patients (2 females, 4 males, average age 65.3 years) treated with Gamma Knife radiosurgery, 40 Gy/50% isodose line underwent 1.5Tesla MR trigeminal nerve. Target accuracy was assessed from deviation of the coordinates of the target compared with the center of enhancement on post MRI. Radiation dose delivered at the borders of contrast enhancement was evaluated. Results: The median deviation of the coordinates between the intended target and the center of contrast enhancement was within 1mm. The radiation doses fitting within the borders of the contrast enhancement the target ranged from 37.5 to 40 Gy. Trigeminal tractography accurately detected the radiosurgical target. Radiosurgery resulted in 47% drop in FA values at the target with no significant change in FA outside the target, suggesting that radiosurgery primarily affects myelin. Tractography was more sensitive, since FA changes were detected regardless of trigeminal nerve enhancement. Conclusion: The median deviation found in clinical assessment of gamma knife treatment for TN Is low and compatible with its high rate of efficiency. DTI parameters accurately detect the effects of focal radiosurgery on the trigeminal nerve, serving as an in vivo imaging tool to study TN. This study is a proof of principle for further assessment of DTI parameters to understand the pathophysiology of TN and treatment

Initiated chemical vapor deposited nanoadhesive for bonding National Ignition Facility's targets

Energy Technology Data Exchange (ETDEWEB)

Lee, Tom [Univ. of California, Berkeley, CA (United States)

2016-05-19

Currently, the target fabrication scientists in National Ignition Facility Directorate at Lawrence Livermore National Laboratory (LLNL) is studying the propagation force resulted from laser impulses impacting a target. To best study this, they would like the adhesive used to glue the target substrates to be as thin as possible. The main objective of this research project is to create adhesive glue bonds for NIF’s targets that are ≤ 1 μm thick. Polyglycidylmethacrylate (PGMA) thin films were coated on various substrates using initiated chemical vapor deposition (iCVD). Film quality studies using white light interferometry reveal that the iCVD PGMA films were smooth. The coated substrates were bonded at 150 °C under vacuum, with low inflow of Nitrogen. Success in bonding most of NIF’s mock targets at thicknesses ≤ 1 μm indicates that our process is feasible in bonding the real targets. Key parameters that are required for successful bonding were concluded from the bonding results. They include inert bonding atmosphere, sufficient contact between the PGMA films, and smooth substrates. Average bond strength of 0.60 MPa was obtained from mechanical shearing tests. The bonding failure mode of the sheared interfaces was observed to be cohesive. Future work on this project will include reattempt to bond silica aerogel to iCVD PGMA coated substrates, stabilize carbon nanotube forests with iCVD PGMA coating, and kinetics study of PGMA thermal crosslinking.

Targeting small airways in asthma: Improvement in clinical benefit?

DEFF Research Database (Denmark)

Ulrik, Charlotte Suppli; Lange, Peter

2010-01-01

Background and Aim:  Disease control is not achieved in a substantial proportion of patients with asthma. Recent advances in aerosol formulations and delivery devices may offer more effective therapy. This review will focus on the importance and potential clinical benefit of targeting the lung...... half the daily dose with no increased risk of systemic effects. Clinical studies of adults with asthma have shown a greater effect of ultrafine ICS, compared with non-ultrafine ICS, on quality of life, small airway patency, and markers of pulmonary and systemic inflammation, but no difference...... with regard to conventional clinical indices of lung function and asthma control. Conclusions:  Asthma patients treated with ultrafine ICS, compared with non-ultrafine ICS, have at least similar chance of achieving asthma control at a lower daily dose. Further clinical studies are needed to explore whether...

Targeting small airways in asthma: Improvement in clinical benefit?

DEFF Research Database (Denmark)

Ulrik, Charlotte Suppli; Lange, Peter

2010-01-01

Background and Aim: Disease control is not achieved in a substantial proportion of patients with asthma. Recent advances in aerosol formulations and delivery devices may offer more effective therapy. This review will focus on the importance and potential clinical benefit of targeting the lung...... half the daily dose with no increased risk of systemic effects. Clinical studies of adults with asthma have shown a greater effect of ultrafine ICS, compared with non-ultrafine ICS, on quality of life, small airway patency, and markers of pulmonary and systemic inflammation, but no difference...... with regard to conventional clinical indices of lung function and asthma control. Conclusions: Asthma patients treated with ultrafine ICS, compared with non-ultrafine ICS, have at least similar chance of achieving asthma control at a lower daily dose. Further clinical studies are needed to explore whether...

Prognostic significance of clinical seizures after cardiac arrest and target temperature management

DEFF Research Database (Denmark)

Lybeck, Anna; Friberg, Hans; Aneman, Anders

2017-01-01

AIM: Clinical seizures are common after cardiac arrest and predictive of a poor neurological outcome. Seizures may be myoclonic, tonic-clonic or a combination of seizure types. This study reports the incidence and prognostic significance of clinical seizures in the target temperature management (...

Targeting dormant micrometastases: rationale, evidence to date and clinical implications.

Science.gov (United States)

Hurst, Robert E; Bastian, Anja; Bailey-Downs, Lora; Ihnat, Michael A

2016-03-01

In spite of decades of research, cancer survival has increased only modestly. This is because most research is based on models of primary tumors. Slow recognition has begun that disseminated, dormant cancer cells (micrometastatic cells) that are generally resistant to chemotherapy are the culprits in recurrence, and until these are targeted effectively we can expect only slow progress in increasing overall survival from cancer. This paper reviews efforts to understand the mechanisms by which cancer cells can become dormant, and thereby identify potential targets and drugs either on the market or in clinical trials that purport to prevent metastasis. This review targets the most recent literature because several excellent reviews have covered the literature from more than two years ago. The paper also describes recent work in the authors' laboratories to develop a screening-based approach that does not require understanding of mechanisms of action or the molecular target. Success of this approach shows that targeting micrometastatic cells is definitely feasible.

Materials considerations for the National Spallation Neutron Source target

International Nuclear Information System (INIS)

Mansur, L.K.; DiStefano, J.R.; Farrell, K.; Lee, E.H.; Pawel, S.J.; Wechsler, M.S.

1997-08-01

The National Spallation Neutron Source (NSNS), in which neutrons are generated by bombarding a liquid mercury target with 1 GeV protons, will place extraordinary demands on materials performance. The target structural material will operate in an aggressive environment, subject to intense fluxes of high energy protons, neutrons, and other particles, while exposed to liquid mercury and to water. Components that require special consideration include the Hg liquid target container and protective shroud, beam windows, support structures, moderator containers, and beam tubes. In response to these demands a materials R and D program has been developed for the NSNS that includes: selection of materials; calculations of radiation damage; irradiations, post irradiation testing, and characterization; compatibility testing and characterization; design and implementation of a plan for monitoring of materials performance in service; and materials engineering and technical support to the project. Irradiations are being carried out in actual and simulated spallation environments. Compatibility experiments in Hg are underway to ascertain whether the phenomena of liquid metal embrittlement and temperature gradient mass transfer will be significant. Results available to date are assessed in terms of the design and operational performance of the facility

Tritium and ignition target management at the National Ignition Facility.

Science.gov (United States)

Draggoo, Vaughn

2013-06-01

Isotopic mixtures of hydrogen constitute the basic fuel for fusion targets of the National Ignition Facility (NIF). A typical NIF fusion target shot requires approximately 0.5 mmoles of hydrogen gas and as much as 750 GBq (20 Ci) of 3H. Isotopic mix ratios are specified according to the experimental shot/test plan and the associated test objectives. The hydrogen isotopic concentrations, absolute amounts, gas purity, configuration of the target, and the physical configuration of the NIF facility are all parameters and conditions that must be managed to ensure the quality and safety of operations. An essential and key step in the preparation of an ignition target is the formation of a ~60 μm thick hydrogen "ice" layer on the inner surface of the target capsule. The Cryogenic Target Positioning System (Cryo-Tarpos) provides gas handling, cyro-cooling, x-ray imaging systems, and related instrumentation to control the volumes and temperatures of the multiphase (solid, liquid, and gas) hydrogen as the gas is condensed to liquid, admitted to the capsule, and frozen as a single spherical crystal of hydrogen in the capsule. The hydrogen fuel gas is prepared in discrete 1.7 cc aliquots in the LLNL Tritium Facility for each ignition shot. Post-shot hydrogen gas is recovered in the NIF Tritium Processing System (TPS). Gas handling systems, instrumentation and analytic equipment, material accounting information systems, and the shot planning systems must work together to ensure that operational and safety requirements are met.

Assessing sample representativeness in randomized controlled trials: application to the National Institute of Drug Abuse Clinical Trials Network.

Science.gov (United States)

Susukida, Ryoko; Crum, Rosa M; Stuart, Elizabeth A; Ebnesajjad, Cyrus; Mojtabai, Ramin

2016-07-01

To compare the characteristics of individuals participating in randomized controlled trials (RCTs) of treatments of substance use disorder (SUD) with individuals receiving treatment in usual care settings, and to provide a summary quantitative measure of differences between characteristics of these two groups of individuals using propensity score methods. Design Analyses using data from RCT samples from the National Institute of Drug Abuse Clinical Trials Network (CTN) and target populations of patients drawn from the Treatment Episodes Data Set-Admissions (TEDS-A). Settings Multiple clinical trial sites and nation-wide usual SUD treatment settings in the United States. A total of 3592 individuals from 10 CTN samples and 1 602 226 individuals selected from TEDS-A between 2001 and 2009. Measurements The propensity scores for enrolling in the RCTs were computed based on the following nine observable characteristics: sex, race/ethnicity, age, education, employment status, marital status, admission to treatment through criminal justice, intravenous drug use and the number of prior treatments. Findings The proportion of those with ≥ 12 years of education and the proportion of those who had full-time jobs were significantly higher among RCT samples than among target populations (in seven and nine trials, respectively, at P difference in the mean propensity scores between the RCTs and the target population was 1.54 standard deviations and was statistically significant at P different from individuals receiving treatment in usual care settings. Notably, RCT participants tend to have more years of education and a greater likelihood of full-time work compared with people receiving care in usual care settings. © 2016 Society for the Study of Addiction.

Clinical Evaluation of Stereotactic Target Localization Using 3-Tesla MRI for Radiosurgery Planning

International Nuclear Information System (INIS)

MacFadden, Derek; Zhang Beibei; Brock, Kristy K.; Hodaie, Mojgan; Laperriere, Normand; Schwartz, Michael; Tsao, May; Stainsby, Jeffrey; Lockwood, Gina; Mikulis, David; Menard, Cynthia

2010-01-01

Purpose: Increasing the magnetic resonance imaging (MRI) field strength can improve image resolution and quality, but concerns remain regarding the influence on geometric fidelity. The objectives of the present study were to spatially investigate the effect of 3-Tesla (3T) MRI on clinical target localization for stereotactic radiosurgery. Methods and Materials: A total of 39 patients were enrolled in a research ethics board-approved prospective clinical trial. Imaging (1.5T and 3T MRI and computed tomography) was performed after stereotactic frame placement. Stereotactic target localization at 1.5T vs. 3T was retrospectively analyzed in a representative cohort of patients with tumor (n = 4) and functional (n = 5) radiosurgical targets. The spatial congruency of the tumor gross target volumes was determined by the mean discrepancy between the average gross target volume surfaces at 1.5T and 3T. Reproducibility was assessed by the displacement from an averaged surface and volume congruency. Spatial congruency and the reproducibility of functional radiosurgical targets was determined by comparing the mean and standard deviation of the isocenter coordinates. Results: Overall, the mean absolute discrepancy across all patients was 0.67 mm (95% confidence interval, 0.51-0.83), significantly .4), and the gross target volume surface mean displacements were similar within and between users. The overall average isocenter coordinate discrepancy for the functional targets at 1.5T and 3T was 0.33 mm (95% confidence interval, 0.20-0.48), with no patient-specific differences between the mean values (p >.2) or standard deviations (p >.1). Conclusion: Our results have provided clinically relevant evidence supporting the spatial validity of 3T MRI for use in stereotactic radiosurgery under the imaging conditions used.

Target experimental area and systems of the U.S. National Ignition Facility

International Nuclear Information System (INIS)

Tobin, M; Van Wonterghem, B; MacGowan, B J; Hibbard, W; Kalantar, D; Lee, F D; Pittenger, L; Wong, K

1999-01-01

One of the major goals of the US National Ignition Facility is the demonstration of laser driven fusion ignition and burn of targets by inertial confinement and provide capability for a wide variety of high energy density physics experiments. The NIF target area houses the optical systems required to focus the 192 beamlets to a target precisely positioned at the center of the 10 meter diameter, 10-cm thick aluminum target chamber. The chamber serves as mounting surface for the 48 final optics assemblies, the target alignment and positioning equipment, and the target diagnostics. The internal surfaces of the chamber are protected by louvered steel beam dumps. The target area also provides the necessary shielding against target emission and environmental protection equipment. Despite its complexity, the design provides the flexibility to accommodate the needs of the various NIF user groups, such as direct and indirect drive irradiation geometries, modular final optics design, capability to handle cryogenic targets, and easily re-configurable diagnostic instruments. Efficient target area operations are ensured by using line-replaceable designs for systems requiring frequent inspection, maintenance and reconfiguration, such as the final optics, debris shields, phase plates and the diagnostic instruments. A precision diagnostic instrument manipulator (DIMS) allows fast removal and precise repositioning of diagnostic instruments. In addition the authors describe several activities to enhance the target chamber availability, such as the target debris mitigation, the use of standard experimental configurations and the development of smart shot operations planning tools

Characteristics of adults with anxiety or depression treated at an internet clinic: comparison with a national survey and an outpatient clinic.

Science.gov (United States)

Titov, Nickolai; Andrews, Gavin; Kemp, Alice; Robinson, Emma

2010-05-28

There is concern that people seeking treatment over the Internet for anxiety or depressive disorders may not resemble the general population or have less severe disorders than patients attending outpatient clinics or cases identified in community surveys. Thus the response to treatment in Internet based trials might not generalize. We reviewed the characteristics of applicants to an Australian Internet-based treatment clinic for anxiety and depression, and compared this sample with people from a national epidemiological survey and a sample of patients at a specialist outpatient anxiety and depression clinic. Participants included 774 volunteers to an Internet clinic, 454 patients at a specialist anxiety disorders outpatient clinic, and 627 cases identified in a national epidemiological survey. Main measures included demographic characteristics, and severity of symptoms as measured by the Kessler 10-Item scale (K-10), the 12-item World Health Organisation Disability Assessment Schedule second edition (WHODAS-II), the Penn State Worry Questionnaire (PSWQ), the Body Sensations Questionnaire (BSQ), the Automatic Cognitions Questionnaire (ACQ), the Social Interaction Anxiety Scale (SIAS) and the Social Phobia Scale (SPS). The severity of symptoms of participants attending the two clinics was similar, and both clinic samples were more severe than cases in the epidemiological survey. The Internet clinic and national samples were older and comprised more females than those attending the outpatient clinic. The Internet clinic sample were more likely to be married than the other samples. The Internet clinic and outpatient clinic samples had higher levels of educational qualifications than the national sample, but employment status was similar across groups. The Internet clinic sample have disorders as severe as those attending an outpatient clinic, but with demographic characteristics more consistent with the national sample. These data indicate that the benefits of Internet

Characteristics of adults with anxiety or depression treated at an internet clinic: comparison with a national survey and an outpatient clinic.

Directory of Open Access Journals (Sweden)

Nickolai Titov

2010-05-01

Full Text Available There is concern that people seeking treatment over the Internet for anxiety or depressive disorders may not resemble the general population or have less severe disorders than patients attending outpatient clinics or cases identified in community surveys. Thus the response to treatment in Internet based trials might not generalize.We reviewed the characteristics of applicants to an Australian Internet-based treatment clinic for anxiety and depression, and compared this sample with people from a national epidemiological survey and a sample of patients at a specialist outpatient anxiety and depression clinic. Participants included 774 volunteers to an Internet clinic, 454 patients at a specialist anxiety disorders outpatient clinic, and 627 cases identified in a national epidemiological survey. Main measures included demographic characteristics, and severity of symptoms as measured by the Kessler 10-Item scale (K-10, the 12-item World Health Organisation Disability Assessment Schedule second edition (WHODAS-II, the Penn State Worry Questionnaire (PSWQ, the Body Sensations Questionnaire (BSQ, the Automatic Cognitions Questionnaire (ACQ, the Social Interaction Anxiety Scale (SIAS and the Social Phobia Scale (SPS.The severity of symptoms of participants attending the two clinics was similar, and both clinic samples were more severe than cases in the epidemiological survey. The Internet clinic and national samples were older and comprised more females than those attending the outpatient clinic. The Internet clinic sample were more likely to be married than the other samples. The Internet clinic and outpatient clinic samples had higher levels of educational qualifications than the national sample, but employment status was similar across groups.The Internet clinic sample have disorders as severe as those attending an outpatient clinic, but with demographic characteristics more consistent with the national sample. These data indicate that the benefits

Raising Public Awareness of Clinical Trials: Development of Messages for a National Health Communication Campaign.

Science.gov (United States)

Massett, Holly A; Dilts, David M; Bailey, Robert; Berktold, Jennifer; Ledsky, Rebecca; Atkinson, Nancy L; Mishkin, Grace; Denicoff, Andrea; Padberg, Rose Mary; Allen, Marin P; Silver, Karen; Carrington, Kelli; Johnson, Lenora E

2017-05-01

Clinical trials are essential for developing new and effective treatments and improving patient quality of life; however, many trials cannot answer their primary research questions because they fall short of their recruitment goals. This article reports the results of formative research conducted in two populations, the public and primary care physicians, to identify messages that may raise awareness and increase interest in clinical trials and be used in a national communication campaign. Results suggested that participants were primarily motivated to participate in clinical trials out of a self-interest to help themselves first. Messages illustrated that current treatments were tested via clinical trials, helped normalize trials as routine practices, and reduced concerns over trying something new first. Participants wanted messages that portray trials as state-of-the-art choices that offer some hope, show people like themselves, and are described in a clear, concise manner with actionable steps for them to take. The study revealed some differences in message salience, with healthy audiences exhibiting lower levels of interest. Our results suggest that targeted messages are needed, and that communication with primary health-care providers is an important and necessary component in raising patient awareness of the importance of clinical trials.

Implementation of the Polarized HD target at the Thomas Jefferson National Accelerator Facility

International Nuclear Information System (INIS)

Chaden Djalali; David Tedeschi

2007-01-01

The original goal of this proposal was to study frozen spin polarized targets (HD target and other technologies) and produce a conceptual design report for the implementation of such a target in the HALL B detector of the Thomas Jefferson National Accelerator Facility (JLab). During the first two years of the proposal, we came to the conclusion that the best suited target for JLab was a frozen spin target and helped with the design of such a target. We have not only achieved our original goal but have exceeded it by being involved in the actual building and testing of parts the target. The main reason for this success has been the hiring of a senior research associate, Dr. Oleksandr Dzyubak, who had more than 10 years of experience in the field of frozen spin polarized targets. The current grant has allowed the USC nuclear physics group to strengthen its role in the JLab collaboration and make important contribution to both the detector development and the scientific program

Review on clinical trials of targeted treatments in malignant mesothelioma

DEFF Research Database (Denmark)

Jakobsen, Jan Nyrop; Sørensen, Jens Benn

2011-01-01

Malignant mesothelioma (MM) is an aggressive tumor of the serosal surfaces with a poor prognosis. Advances in the understanding of tumor biology have led to the development of several targeted treatments, which have been evaluated in clinical trials. This article is a comprehensive review of all...

SU-E-J-34: Clinical Evaluation of Targeting Accuracy and Tractogrphy Delineation of Radiosurgery

Energy Technology Data Exchange (ETDEWEB)

Juh, R; Suh, T; Kim, Y; Han, J; Kim, C; Oh, C; Kim, D [Seoul National University Bundang Hospital (Korea, Republic of)

2014-06-01

Purpose: Focal radiosurgery is a common treatment modality for trigeminal neuralgia (TN), a neuropathic facial pain condition. Assessment of treatment effectiveness is primarily clinical, given the paucity of investigational tools to assess trigeminal nerve changes. The efficiency of radiosurgery is related to its highly precise targeting. We assessed clinically the targeting accuracy of radiosurgery with Gamma knife. We hypothesized that trigeminal tractography provides more information than 2D-MR imaging, allowing detection of unique, focal changes in the target area after radiosurgery. Methods: Sixteen TN patients (2 females, 4 male, average age 65.3 years) treated with Gamma Knife radiosurgery, 40 Gy/50% isodose line underwent 1.5Tesla MR trigeminal nerve . Target accuracy was assessed from deviation of the coordinates of the target compared with the center of enhancement on post MRI. Radiation dose delivered at the borders of contrast enhancement was evaluated Results: The median deviation of the coordinates between the intended target and the center of contrast enhancement was within 1mm. The radiation doses fitting within the borders of the contrast enhancement the target ranged from 37.5 to 40 Gy. Trigeminal tractography accurately detected the radiosurgical target. Radiosurgery resulted in 47% drop in FA values at the target with no significant change in FA outside the target, suggesting that radiosurgery primarily affects myelin. Tractography was more sensitive, since FA changes were detected regardless of trigeminal nerve enhancement Conclusion: The median deviation found in clinical assessment of gamma knife treatment for TN Is low and compatible with its high rate of efficiency. DTI parameters accurately detect the effects of focal radiosurgery on the trigeminal nerve, serving as an in vivo imaging tool to study TN. This study is a proof of principle for further assessment of DTI parameters to understand the pathophysiology of TN and treatment effects.

Completeness and validity in a national clinical thyroid cancer database

DEFF Research Database (Denmark)

Londero, Stefano Christian; Mathiesen, Jes Sloth; Krogdahl, Annelise

2014-01-01

cancer database: DATHYRCA. STUDY DESIGN AND SETTING: National prospective cohort. Denmark; population 5.5 million. Completeness of case ascertainment was estimated by the independent case ascertainment method using three governmental registries as a reference. The reabstracted record method was used...... to appraise the validity. For validity assessment 100 cases were randomly selected from the DATHYRCA database; medical records were used as a reference. RESULT: The database held 1934 cases of thyroid carcinoma and completeness of case ascertainment was estimated to 90.9%. Completeness of registration......BACKGROUND: Although a prospective national clinical thyroid cancer database (DATHYRCA) has been active in Denmark since January 1, 1996, no assessment of data quality has been performed. The purpose of the study was to evaluate completeness and data validity in the Danish national clinical thyroid...

Comprehensive target populations for current active safety systems using national crash databases.

Science.gov (United States)

Kusano, Kristofer D; Gabler, Hampton C

2014-01-01

The objective of active safety systems is to prevent or mitigate collisions. A critical component in the design of active safety systems is the identification of the target population for a proposed system. The target population for an active safety system is that set of crashes that a proposed system could prevent or mitigate. Target crashes have scenarios in which the sensors and algorithms would likely activate. For example, the rear-end crash scenario, where the front of one vehicle contacts another vehicle traveling in the same direction and in the same lane as the striking vehicle, is one scenario for which forward collision warning (FCW) would be most effective in mitigating or preventing. This article presents a novel set of precrash scenarios based on coded variables from NHTSA's nationally representative crash databases in the United States. Using 4 databases (National Automotive Sampling System-General Estimates System [NASS-GES], NASS Crashworthiness Data System [NASS-CDS], Fatality Analysis Reporting System [FARS], and National Motor Vehicle Crash Causation Survey [NMVCCS]) the scenarios developed in this study can be used to quantify the number of police-reported crashes, seriously injured occupants, and fatalities that are applicable to proposed active safety systems. In this article, we use the precrash scenarios to identify the target populations for FCW, pedestrian crash avoidance systems (PCAS), lane departure warning (LDW), and vehicle-to-vehicle (V2V) or vehicle-to-infrastructure (V2I) systems. Crash scenarios were derived using precrash variables (critical event, accident type, precrash movement) present in all 4 data sources. This study found that these active safety systems could potentially mitigate approximately 1 in 5 of all severity and serious injury crashes in the United States and 26 percent of fatal crashes. Annually, this corresponds to 1.2 million all severity, 14,353 serious injury (MAIS 3+), and 7412 fatal crashes. In addition

Clinical Research Nursing: A Critical Resource in the National Research Enterprise

Science.gov (United States)

Hastings, Clare E.; Fisher, Cheryl A.; McCabe, Margaret A.

2012-01-01

Translational clinical research has emerged as an important priority for the national research enterprise, with a clearly stated mandate to deliver prevention strategies, treatments and cures based on scientific innovations faster to the public. Within this national effort, a lack of consensus persists concerning the need for clinical nurses with expertise and specialized training in study implementation and the delivery of care to research participants. This paper reviews efforts to define and document the role of practicing nurses in implementing studies and coordinating clinical research in a variety of clinical settings and differentiates this clinical role from the role of nurses as scientists and principal investigators. We propose an agenda for building evidence that having nurses provide and coordinate study treatments and procedures can potentially improve research efficiency, participant safety, and the quality of research data. We also provide recommendations for the development of the emerging specialty of clinical research nursing. PMID:22172370

The physics basis for ignition using indirect-drive targets on the National Ignition Facility

International Nuclear Information System (INIS)

Lindl, John D.; Amendt, Peter; Berger, Richard L.; Glendinning, S. Gail; Glenzer, Siegfried H.; Haan, Steven W.; Kauffman, Robert L.; Landen, Otto L.; Suter, Laurence J.

2004-01-01

The 1990 National Academy of Science final report of its review of the Inertial Confinement Fusion Program recommended completion of a series of target physics objectives on the 10-beam Nova laser at the Lawrence Livermore National Laboratory as the highest-priority prerequisite for proceeding with construction of an ignition-scale laser facility, now called the National Ignition Facility (NIF). These objectives were chosen to demonstrate that there was sufficient understanding of the physics of ignition targets that the laser requirements for laboratory ignition could be accurately specified. This research on Nova, as well as additional research on the Omega laser at the University of Rochester, is the subject of this review. The objectives of the U.S. indirect-drive target physics program have been to experimentally demonstrate and predictively model hohlraum characteristics, as well as capsule performance in targets that have been scaled in key physics variables from NIF targets. To address the hohlraum and hydrodynamic constraints on indirect-drive ignition, the target physics program was divided into the Hohlraum and Laser-Plasma Physics (HLP) program and the Hydrodynamically Equivalent Physics (HEP) program. The HLP program addresses laser-plasma coupling, x-ray generation and transport, and the development of energy-efficient hohlraums that provide the appropriate spectral, temporal, and spatial x-ray drive. The HEP experiments address the issues of hydrodynamic instability and mix, as well as the effects of flux asymmetry on capsules that are scaled as closely as possible to ignition capsules (hydrodynamic equivalence). The HEP program also addresses other capsule physics issues associated with ignition, such as energy gain and energy loss to the fuel during implosion in the absence of alpha-particle deposition. The results from the Nova and Omega experiments approach the NIF requirements for most of the important ignition capsule parameters, including

[Contribution of Chilean research to the formulation of national clinical guidelines].

Science.gov (United States)

Núñez, Paulina F; Torres, Adrián C; Armas, Rodolfo M

2014-12-01

In Chile, 80 diseases were included in a health care system called Health Care Guarantees (GES) and clinical guidelines were elaborated for their management. To assess the scientific background of guidelines and if they were based on research financed by the Chilean National Commission for Science and Technology. The references of the 82 guidelines developed for 80 diseases were reviewed, registering their number, authors, country of origin and funding source. The guidelines had a total of 6,604 references. Of these, only 185 were Chilean (2.8%) and five (0.08%) originated from research financed by the National Commission for Science and Technology. The contribution of research funded by national agencies to the formulation of clinical guidelines is minimal.

75 FR 59276 - National Institute of Allergy and Infectious Diseases; Notice of Closed Meetings

Science.gov (United States)

2010-09-27

... Infectious Diseases Special Emphasis Panel; Targeted Clinical Trials To Reduce the Risk of Antimicrobial... Diseases Special Emphasis Panel; Targeted Clinical Trials To Reduce the Risk of Antimicrobial Resistance... Transplantation Research; 93.856, Microbiology and Infectious Diseases Research, National Institutes of Health...

CFD analysis of a liquid mercury target for the National Spallation Neutron Source

International Nuclear Information System (INIS)

Wendel, M.W.; Tov, M.S.

1997-01-01

Computational fluid dynamics (CFD) is being used to analyze the design of the National Spallation Neutron Source (NSNS) target. The target is subjected to the neutronic (internal) heat generation that results from the proton collisions with the mercury nuclei. The liquid mercury simultaneously serves as the neutronic target medium, transports away the heat generated within itself, and cools the metallic target structure. Recirculation and stagnation zones within the target are of particular concern because of the likelihood that they will result in local hot spots. These zones exist because the most feasible target designs include a complete U-turn flow redirection. Although the primary concern is that the target is adequately cooled, the pressure drop from inlet to outlet must also be considered because pressure drop directly affects structural loading and required pumping power. Various design options have been considered in an effort to satisfy these design criteria. Significant improvements to the design have been recommended based on the results. Detailed results are presented for the current target design including a comparison with published pressure-drop data. Comparisons are also made with forced convection heat transfer data for liquid mercury flow in circular tubes

The National Institute of Dental Research Clinical Dental Staff Fellowship.

Science.gov (United States)

Baum, Bruce J.; And Others

1988-01-01

A program in one of the National Institutes of Health offers clinical training fellowships as a means of training potential dental school faculty by providing both unique clinical skills and high-quality research experience. The program was developed in response to a perceived need for change in academic dentistry. (MSE)

Analysis of quality data based on national clinical databases

DEFF Research Database (Denmark)

Utzon, Jan; Petri, A.L.; Christophersen, S.

2009-01-01

extent the selection of patients, random variation, confounding and inconsistency may have influenced results. The aim of this article is to summarize aspects of clinical healthcare data analyses provided from the national clinical quality databases and to show how data may be presented in a way which......There is little agreement on the philosophy of measuring clinical quality in health care. How data should be analyzed and transformed to healthcare information is an ongoing discussion. To accept a difference in quality between health departments as a real difference, one should consider to which...

Clinical reasoning of Filipino physical therapists: Experiences in a developing nation.

Science.gov (United States)

Rotor, Esmerita R; Capio, Catherine M

2018-03-01

Clinical reasoning is essential for physical therapists to engage in the process of client care, and has been known to contribute to professional development. The literature on clinical reasoning and experiences have been based on studies from Western and developed nations, from which multiple influencing factors have been found. A developing nation, the Philippines, has distinct social, economic, political, and cultural circumstances. Using a phenomenological approach, this study explored experiences of Filipino physical therapists on clinical reasoning. Ten therapists working in three settings: 1) hospital; 2) outpatient clinic; and 3) home health were interviewed. Major findings were: a prescription-based referral system limited clinical reasoning; procedural reasoning was a commonly experienced strategy while diagnostic and predictive reasoning were limited; factors that influenced clinical reasoning included practice setting and the professional relationship with the referring physician. Physical therapists' responses suggested a lack of autonomy in practice that appeared to stifle clinical reasoning. Based on our findings, we recommend that the current regulations governing PT practice in the Philippines may be updated, and encourage educators to strengthen teaching approaches and strategies that support clinical reasoning. These recommendations are consistent with the global trend toward autonomous practice.

Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer.

Science.gov (United States)

Matsuda, Naoko; Lim, Bora; Wang, Xiaoping; Ueno, Naoto T

2017-04-01

Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast cancer. Areas covered: This review focuses on the role of the EGFR pathway and the investigational drugs that target EGFR for breast cancer. Expert opinion: Recent studies have indicated that EGFR targeted therapy for breast cancer has some promising effects for patients with triple-negative breast cancer, basal-like breast cancer, and inflammatory breast cancer. However, predictive and prognostic biomarkers for EGFR targeted therapy have not been identified. The overexpression or amplification of EGFR itself may not be the true factor of induction of the canonical pathway as an oncogenic driver of breast cancer. Instead, downstream, non-canonical pathways related to EGFR may contribute to some aspects of the biological behavior of breast cancer; therefore, the blockade of the receptor could result in sufficient suppression of downstream pathways to inhibit the aggressive behavior of breast cancer. Mechanistic studies to investigate the dynamic interaction between the EGFR pathway and non-canonical pathways are warranted.

Developing clinical practice guidelines: target audiences, identifying topics for guidelines, guideline group composition and functioning and conflicts of interest.

Science.gov (United States)

Eccles, Martin P; Grimshaw, Jeremy M; Shekelle, Paul; Schünemann, Holger J; Woolf, Steven

2012-07-04

Clinical practice guidelines are one of the foundations of efforts to improve health care. In 1999, we authored a paper about methods to develop guidelines. Since it was published, the methods of guideline development have progressed both in terms of methods and necessary procedures and the context for guideline development has changed with the emergence of guideline clearing houses and large scale guideline production organisations (such as the UK National Institute for Health and Clinical Excellence). It therefore seems timely to, in a series of three articles, update and extend our earlier paper. In this first paper we discuss: the target audience(s) for guidelines and their use of guidelines; identifying topics for guidelines; guideline group composition (including consumer involvement) and the processes by which guideline groups function and the important procedural issue of managing conflicts of interest in guideline development.

MR coronary angiography with breath-hold targeted volumes: preliminary clinical results

NARCIS (Netherlands)

R.J.M. van Geuns (Robert Jan); P.A. Wielopolski (Piotr); H.G. de Bruin (Hein); B.J.W.M. Rensing (Benno); M. Hulshoff (Maarten); P.M.A. van Ooijen (Peter); P.J. de Feyter (Pim); M. Oudkerk (Matthijs)

2000-01-01

textabstractPURPOSE: To assess the clinical value of a magnetic resonance (MR) coronary angiography strategy involving a small targeted volume to image one coronary segment in a single breath hold for the detection of greater than 50% stenosis. MATERIALS AND METHODS:

Inflammatory therapeutic targets in coronary atherosclerosis – from molecular biology to clinical application

Directory of Open Access Journals (Sweden)

Fabian eLinden

2014-11-01

Full Text Available Atherosclerosis is the leading cause of death worldwide. Over the past two decades, it has been clearly recognized that atherosclerosis is an inflammatory disease of the arterial wall. Accumulating data from animal experiments have supported this hypothesis, however, clinical applications making use of this knowledge remain scarce. In spite of optimal interventional and medical therapy, the risk for recurrent myocardial infarction remains by about 20% over three years after acute coronary syndromes, novel therapies to prevent atherogenesis or treat atherosclerosis are urgently needed. This review summarizes selected potential molecu-lar inflammatory targets that may be of clinical relevance. We also review recent and ongoing clinical trails that target inflammatory processes aiming at preventing adverse cardiovascular events. Overall, it seems surprising that translation of basic science into clinical practice has not been a great success. In conclusion, we propose to focus on specific efforts that promote translational science in order to improve outcome and prognosis of patients suffering from atherosclerosis.

Evaluation of Australian soup manufacturer compliance with national sodium reduction targets.

Science.gov (United States)

Levi, Rebecca; Probst, Yasmine; Crino, Michelle; Dunford, Elizabeth

2018-04-01

Packaged foods dominate Australia's food supply and are important contributors to nutrition-related disease. To help address this problem, the Food and Health Dialogue (FHD) was launched in 2009, setting voluntary sodium reduction targets for various categories of packaged foods. The aim of this study was to examine the food industry's progress and compliance with the FHD sodium reduction targets for soup products. Nutritional information was collected from product labels of all soup products available from four major Australian supermarkets annually between 2011 and 2014. Products were assigned to categories in line with those in the FHD. The proportion of soup products meeting sodium reduction targets was examined by (i) soup category; (ii) FHD participant status; and (iii) manufacturer. A 6% reduction in sodium levels in soups overall was found from 2011 to 2014 (P = 0.002). Significant reductions were observed for FHD participants (P < 0.05 for all) but not for non-participants. In 2014, 67% dry soups and 76% of wet soups met national sodium reduction targets. Despite the majority of soup products meeting the sodium reduction targets specified by the FHD, re-evaluation of the targets may be required to further reduce sodium levels in soups. Manufacturers participating in the FHD are likely to be driving sodium reductions in the Australian soup market, further highlighting the need for continued government leadership in this area to ensure all manufacturers are actively involved in the process. © 2017 Dietitians Association of Australia.

Reengineering the National Clinical and Translational Research Enterprise: The Strategic Plan of the National Clinical and Translational Science Awards Consortium

Science.gov (United States)

Reis, Steven E.; Berglund, Lars; Bernard, Gordon R.; Califf, Robert M.; FitzGerald, Garret A.; Johnson, Peter C.

2009-01-01

Advances in human health require the efficient and rapid translation of scientific discoveries into effective clinical treatments; this process in turn depends upon observational data gathered from patients, communities, and public-health research that can be used to guide basic scientific investigation. Such bidirectional translational science, however, faces unprecedented challenges due to the rapid pace of scientific and technological development, as well as the difficulties of negotiating increasingly complex regulatory and commercial environments that overlap the research domain. Further, numerous barriers to translational science have emerged among the nation’s academic research centers, including basic structural and cultural impediments to innovation and collaboration, shortages of trained investigators, and inadequate funding. To address these serious and systemic problems, in 2006, the National Institutes of Health created the Clinical and Translational Science Awards (CTSA) program, which aims to catalyze the transformation of biomedical research at a national level, speeding the discovery and development of therapies, fostering collaboration, engaging communities, and training succeeding generations of clinical and translational researchers. The authors report in detail on the planning process, begun in 2008, that was used to engage stakeholders and to identify, refine, and ultimately implement the CTSA program’s overarching strategic goals. They also discuss the implications and likely impact of this strategic planning process as it is applied among the nation’s academic health centers. PMID:20182119

Targets and criteria for the effective participation of national industry in a domestic nuclear power programme

International Nuclear Information System (INIS)

Py, J.P.

1986-01-01

The interest in maximum use of national resource is common to all countries, the highly industrialized as well as the developing ones. Although benefits can be expected from national participation in a domestic nuclear power programme and may not be limited to this programme, such national participation is restricted by constraining factors: economic, financial, technical and political. Considering the various natures of activities - design, procurement, manufacturing, erection -, their technical difficulties, their potential spin-off effects on the overall industrial development of a country, the paper reviews the materials and components of a nuclear power plants which can be selected as targets for domestic production. The paper also reviews criteria which must be considered in setting these Target materials and components in order to overcome restricting factors to national participation such as cost of national products, financing, investment capability, adequate market size, availability of qualified manpower, industrial capability and quality standards, availability of technology and know-how, conflicts of interests. Some concrete examples drawn from previous experience will illustrate France efforts to overcome these limiting factors [fr

Emergency recompression: clinical audit of service delivery at a national level.

Science.gov (United States)

Ross, John As; Sayer, Martin Dj

2009-03-01

Clinical audit is an essential element to the maintenance or improvement of delivery of any medical service. During the development phase of a National Recompression Registration Service for Scotland, clinical audit was initiated to provide a standardised tool to monitor the quality of outcome with respect to the severity of presentation. A functional audit process was an essential consideration for planned future measurement of treatment efficacy at local (single hyperbaric unit) and national (multiple hyperbaric units) scales. The audit process was designed to be undemanding, robust and informative, irrespective of the experience of treatment centre and of the clinician in charge of treatment. The clinical records from 104 cases of divers with decompression illness were used to derive and evaluate measures of severity and clinical outcome that could be used for audit and quality assurance. The various measures of disease severity were examined against clinical outcome and days spent in care after admission to a hyperbaric unit. An initial version of the clinical audit format that was developed from this process is presented.

Generalizing Evidence From Randomized Clinical Trials to Target Populations

Science.gov (United States)

Cole, Stephen R.; Stuart, Elizabeth A.

2010-01-01

Properly planned and conducted randomized clinical trials remain susceptible to a lack of external validity. The authors illustrate a model-based method to standardize observed trial results to a specified target population using a seminal human immunodeficiency virus (HIV) treatment trial, and they provide Monte Carlo simulation evidence supporting the method. The example trial enrolled 1,156 HIV-infected adult men and women in the United States in 1996, randomly assigned 577 to a highly active antiretroviral therapy and 579 to a largely ineffective combination therapy, and followed participants for 52 weeks. The target population was US people infected with HIV in 2006, as estimated by the Centers for Disease Control and Prevention. Results from the trial apply, albeit muted by 12%, to the target population, under the assumption that the authors have measured and correctly modeled the determinants of selection that reflect heterogeneity in the treatment effect. In simulations with a heterogeneous treatment effect, a conventional intent-to-treat estimate was biased with poor confidence limit coverage, but the proposed estimate was largely unbiased with appropriate confidence limit coverage. The proposed method standardizes observed trial results to a specified target population and thereby provides information regarding the generalizability of trial results. PMID:20547574

Biologics for Targeting Inflammatory Cytokines, Clinical Uses, and Limitations

Directory of Open Access Journals (Sweden)

Peleg Rider

2016-01-01

Full Text Available Proinflammatory cytokines are potent mediators of numerous biological processes and are tightly regulated in the body. Chronic uncontrolled levels of such cytokines can initiate and derive many pathologies, including incidences of autoimmunity and cancer. Therefore, therapies that regulate the activity of inflammatory cytokines, either by supplementation of anti-inflammatory recombinant cytokines or by neutralizing them by using blocking antibodies, have been extensively used over the past decades. Over the past few years, new innovative biological agents for blocking and regulating cytokine activities have emerged. Here, we review some of the most recent approaches of cytokine targeting, focusing on anti-TNF antibodies or recombinant TNF decoy receptor, recombinant IL-1 receptor antagonist (IL-1Ra and anti-IL-1 antibodies, anti-IL-6 receptor antibodies, and TH17 targeting antibodies. We discuss their effects as biologic drugs, as evaluated in numerous clinical trials, and highlight their therapeutic potential as well as emphasize their inherent limitations and clinical risks. We suggest that while systemic blocking of proinflammatory cytokines using biological agents can ameliorate disease pathogenesis and progression, it may also abrogate the hosts defense against infections. Moreover, we outline the rational need to develop new therapies, which block inflammatory cytokines only at sites of inflammation, while enabling their function systemically.

A survey of differentiation methods for national greenhouse gas reduction targets

Energy Technology Data Exchange (ETDEWEB)

Torvanger, Asbjoern; Godal, Odd

1999-11-01

The aim of the report is to contribute to exploring the potential differentiation methods for national greenhouse gas reduction targets. The Kyoto Protocol to the United Nations Framework Convention on Climate Change (UNFCCC) from 1997 established differentiation of targets among countries. A more systematic approach to differentiation would facilitate future negotiations. Three sources of methods or proposals are employed. The first are proposals from the Ad Hoc Group on the Berlin Mandate (AGBM) process from 1995 until the Kyoto Protocol was adopted in December 1997, in all 17 proposals were selected. The second source is the EU`s Triptique approach for differentiation of targets among its member states. The third source is recent academic literature where 8 contributions from the period 1992 to 1998 were included. The proposals are presented in a catalogue style. Based on 4 criteria on the usefulness of proposals or methods for future negotiations we have chosen 5 proposals, a Japanese, French, Norwegian, Brazilian in addition to the EU`s Triptique approach. Some numerical illustrations for the Baltic Sea region are presented. Given the joint Kyoto Protocol reduction target for the region we compare the burden sharing consequences for the proposals. For illustrations we employ the following fairness principles as differentiation methods: 1) The Sovereignty principle. 2) The Egalitarian principle. 3) The Ability to Pay principle. With the aim to evaluate the political feasibility of the various differentiation methods we compare the results across the countries in the Baltic Sea region and divide them into OECD and EIT countries. The outcome of the Kyoto Protocol is interpreted as an example of a politically feasible differentiation scheme. On the basis of the observations we find principles 1) and 2) less interesting. A ranking of the differentiation methods according to political feasibility is made and discussed. Among the countries in the Baltic Sea region

Implementation of Targeted Next Generation Sequencing in Clinical Diagnostics

DEFF Research Database (Denmark)

Larsen, Martin Jakob; Burton, Mark; Thomassen, Mads

Accurate mutation detection is essential in clinical genetic diagnostics of monogenic hereditary diseases. Targeted next generation sequencing (NGS) provides a promising and cost-effective alternative to Sanger sequencing and MLPA analysis currently used in most diagnostic laboratories. One...... of mutation positive controls previously characterized by Sanger/MLPA analysis. Agilent SureSelect Target-Enrichment kits were used for capturing a set of genes associated with hereditary breast and ovarian cancer syndrome and a compilation of genes involved in multiple rare single gene disorders......, respectively. For diagnostics, the sequencing coverage is essential, wherefore a minimum coverage of 30x per nucleotide in the coding regions was used as our primary quality criterion. For the majority of the included genes, we obtained adequate gene coverage, in which we were able to detect 100% of the known...

Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer

Science.gov (United States)

Matsuda, Naoko; Lim, Bora; Wang, Xiaoping; Ueno, Naoto T.

2018-01-01

Introduction Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast cancer. Areas covered This review focuses on the role of the EGFR pathway and the investigational drugs that target EGFR for breast cancer. Expert opinion Recent studies have indicated that EGFR targeted therapy for breast cancer has some promising effects for patients with triple-negative breast cancer, basal-like breast cancer, and inflammatory breast cancer. However, predictive and prognostic biomarkers for EGFR targeted therapy have not been identified. The overexpression or amplification of EGFR itself may not be the true factor of induction of the canonical pathway as an oncogenic driver of breast cancer. Instead, downstream, non-canonical pathways related to EGFR may contribute to some aspects of the biological behavior of breast cancer; therefore, the blockade of the receptor could result in sufficient suppression of downstream pathways to inhibit the aggressive behavior of breast cancer. Mechanistic studies to investigate the dynamic interaction between the EGFR pathway and non-canonical pathways are warranted. PMID:28271910

HIV/AIDS National Strategic Plans of Sub-Saharan African countries: an analysis for gender equality and sex-disaggregated HIV targets.

Science.gov (United States)

Sherwood, Jennifer; Sharp, Alana; Cooper, Bergen; Roose-Snyder, Beirne; Blumenthal, Susan

2017-12-01

National Strategic Plans (NSPs) for HIV/AIDS are country planning documents that set priorities for programmes and services, including a set of targets to quantify progress toward national and international goals. The inclusion of sex-disaggregated targets and targets to combat gender inequality is important given the high disease burden among young women and adolescent girls in Sub-Saharan Africa, yet no comprehensive gender-focused analysis of NSP targets has been performed. This analysis quantitatively evaluates national HIV targets, included in NSPs from eighteen Sub-Saharan African countries, for sex-disaggregation. Additionally, NSP targets aimed at reducing gender-based inequality in health outcomes are compiled and inductively coded to report common themes. On average, in the eighteen countries included in this analysis, 31% of NSP targets include sex-disaggregation (range 0-92%). Three countries disaggregated a majority (>50%) of their targets by sex. Sex-disaggregation in data reporting was more common for targets related to the early phases of the HIV care continuum: 83% of countries included any sex-disaggregated targets for HIV prevention, 56% for testing and linkage to care, 22% for improving antiretroviral treatment coverage, and 11% for retention in treatment. The most common target to reduce gender inequality was to prevent gender-based violence (present in 50% of countries). Other commonly incorporated target areas related to improving women's access to family planning, human and legal rights, and decision-making power. The inclusion of sex-disaggregated targets in national planning is vital to ensure that programmes make progress for all population groups. Improving the availability and quality of indicators to measure gender inequality, as well as evaluating programme outcomes by sex, is critical to tracking this progress. This analysis reveals an urgent need to set specific and separate targets for men and women in order to achieve an equitable

HIV/AIDS National Strategic Plans of Sub-Saharan African countries: an analysis for gender equality and sex-disaggregated HIV targets

Science.gov (United States)

Sherwood, Jennifer; Sharp, Alana; Cooper, Bergen; Roose-Snyder, Beirne; Blumenthal, Susan

2017-01-01

Abstract National Strategic Plans (NSPs) for HIV/AIDS are country planning documents that set priorities for programmes and services, including a set of targets to quantify progress toward national and international goals. The inclusion of sex-disaggregated targets and targets to combat gender inequality is important given the high disease burden among young women and adolescent girls in Sub-Saharan Africa, yet no comprehensive gender-focused analysis of NSP targets has been performed. This analysis quantitatively evaluates national HIV targets, included in NSPs from eighteen Sub-Saharan African countries, for sex-disaggregation. Additionally, NSP targets aimed at reducing gender-based inequality in health outcomes are compiled and inductively coded to report common themes. On average, in the eighteen countries included in this analysis, 31% of NSP targets include sex-disaggregation (range 0–92%). Three countries disaggregated a majority (>50%) of their targets by sex. Sex-disaggregation in data reporting was more common for targets related to the early phases of the HIV care continuum: 83% of countries included any sex-disaggregated targets for HIV prevention, 56% for testing and linkage to care, 22% for improving antiretroviral treatment coverage, and 11% for retention in treatment. The most common target to reduce gender inequality was to prevent gender-based violence (present in 50% of countries). Other commonly incorporated target areas related to improving women’s access to family planning, human and legal rights, and decision-making power. The inclusion of sex-disaggregated targets in national planning is vital to ensure that programmes make progress for all population groups. Improving the availability and quality of indicators to measure gender inequality, as well as evaluating programme outcomes by sex, is critical to tracking this progress. This analysis reveals an urgent need to set specific and separate targets for men and women in order to achieve

The "Conveyor Belt Effect": A Re-Assessment of the Impact of National Targets for Lifelong Learning.

Science.gov (United States)

Gorard, Stephen; Selwyn, Neil; Rees, Gareth

Although the National Targets for Education and Training in England and Wales include indicators for lifelong learning, and the progress towards the targets set for these indicators has been lauded by politicians and other observers, much of this apparent progress is actually accounted for by changes in these same indicators. However, once the…

Credentialism, National Targets, and the Learning Society: Perspectives on Educational Attainment in the UK Steel Industry.

Science.gov (United States)

Fuller, Alison; Unwin, Lorna

1999-01-01

The UK's National Learning Targets for Education and Training, embracing 11- to 21-year-olds, adults, and employers, promote a credentialist approach to economic and social development. This article shows how the steel industry measures up. Using qualifications-based targets as a proxy for adult workforce capability is misguided. (Contains 40…

MR coronary angiography with breath-hold targeted volumes : Preliminary clinical results

NARCIS (Netherlands)

van Geuns, R J; Wielopolski, P A; de Bruin, Hein G.; Rensing, B J; Hulshoff, Marc; van Ooijen, P M; de Feyter, P J; Oudkerk, M

2000-01-01

PURPOSE: To assess the clinical value of a magnetic resonance (MR) coronary angiography strategy involving a small targeted volume to image one coronary segment in a single breath hold for the detection of greater than 50% stenosis. MATERIALS AND METHODS: Thirty-eight patients referred for elective

Clinical and psychosocial predictors of exceeding target length of stay during inpatient stroke rehabilitation.

Science.gov (United States)

Lai, Wesley; Buttineau, Mackenzie; Harvey, Jennifer K; Pucci, Rebecca A; Wong, Anna P M; Dell'Erario, Linda; Bosnyak, Stephanie; Reid, Shannon; Salbach, Nancy M

2017-10-01

In Ontario, Canada, patients admitted to inpatient rehabilitation hospitals post-stroke are classified into rehabilitation patient groups based on age and functional level. Clinical practice guidelines, called quality-based procedures, recommend a target length of stay (LOS) for each group. The study objective was to evaluate the extent to which patients post-stroke at an inpatient rehabilitation hospital are meeting LOS targets and to identify patient characteristics that predict exceeding target LOS. A quantitative, longitudinal study from an inpatient rehabilitation hospital was conducted. Participants included adult patients (≥18 years) with stroke, admitted to an inpatient rehabilitation hospital between 2014 and 2015. The percentage of patients exceeding the recommended target LOS was determined. Logistic regression was performed to identify clinical and psychosocial patient characteristics associated with exceeding target LOS after adjusting for stroke severity. Of 165 patients, 38.8% exceeded their target LOS. Presence of ataxia, recurrent stroke, living alone, absence of a caregiver at admission, and acquiring a caregiver during hospital LOS was each associated with significantly higher odds of exceeding target LOS in comparison to patients without these characteristics after adjusting for stroke severity (p stroke-specific factors may be helpful to adjust LOS expectations and promote efficient resource allocation. This exploratory study was limited to findings from one inpatient rehabilitation hospital. Cross-validation of results using data-sets from multiple rehabilitation hospitals across Ontario is recommended.

Analysis of quality data based on national clinical databases

DEFF Research Database (Denmark)

Utzon, Jan; Petri, A.L.; Christophersen, S.

2009-01-01

There is little agreement on the philosophy of measuring clinical quality in health care. How data should be analyzed and transformed to healthcare information is an ongoing discussion. To accept a difference in quality between health departments as a real difference, one should consider to which...... extent the selection of patients, random variation, confounding and inconsistency may have influenced results. The aim of this article is to summarize aspects of clinical healthcare data analyses provided from the national clinical quality databases and to show how data may be presented in a way which...... is understandable to readers without specialised knowledge of statistics Udgivelsesdato: 2009/9/14...

The contribution of sectoral climate change mitigation options to national targets: a quantitative assessment of dairy production in Kenya

Science.gov (United States)

Brandt, Patric; Herold, Martin; Rufino, Mariana C.

2018-03-01

Reducing greenhouse gas (GHG) emissions from agriculture has become a critical target in national climate change policies. More than 80% of the countries in Sub-Saharan Africa (SSA) refer to the reduction of agricultural emissions, including livestock, in their nationally determined contribution (NDC) to mitigate climate change. The livestock sector in Kenya contributes largely to the gross domestic product and to GHG emissions from the land use sector. The government has recently pledged in its NDC to curb total GHG emissions by 30% by 2030. Quantifying and linking the mitigation potential of farm practices to national targets is required to support realistically the implementation of NDCs. Improvements in feed and manure management represent promising mitigation options for dairy production. This study aimed (i) to assess mitigation and food production benefits of feed and manure management scenarios, including land use changes covering Kenya’s entire dairy production region and (ii) to analyse the contribution of these practices to national targets on milk production and mitigation, and their biophysical feasibility given the availability of arable land. The results indicate that improving forage quality by increasing the use of Napier grass and supplementing dairy concentrates supports Kenya’s NDC target, reduces emission intensities by 26%-31%, partially achieves the national milk productivity target for 2030 by 38%-41%, and shows high feasibility given the availability of arable land. Covering manure heaps may reduce emissions from manure management by 68%. In contrast, including maize silage in cattle diets would not reduce emission intensities due to the risk of ten-fold higher emissions from the conversion of land required to grow additional maize. The shortage of arable land may render the implementation of these improved feed practices largely infeasible. This assessment provides the first quantitative estimates of the potential of feed

A targeted metabolomics approach for clinical diagnosis of inborn errors of metabolism.

Science.gov (United States)

Jacob, Minnie; Malkawi, Abeer; Albast, Nour; Al Bougha, Salam; Lopata, Andreas; Dasouki, Majed; Abdel Rahman, Anas M

2018-09-26

Metabolome, the ultimate functional product of the genome, can be studied through identification and quantification of small molecules. The global metabolome influences the individual phenotype through clinical and environmental interventions. Metabolomics has become an integral part of clinical research and allowed for another dimension of better understanding of disease pathophysiology and mechanism. More than 95% of the clinical biochemistry laboratory routine workload is based on small molecular identification, which can potentially be analyzed through metabolomics. However, multiple challenges in clinical metabolomics impact the entire workflow and data quality, thus the biological interpretation needs to be standardized for a reproducible outcome. Herein, we introduce the establishment of a comprehensive targeted metabolomics method for a panel of 220 clinically relevant metabolites using Liquid chromatography-tandem mass spectrometry (LC-MS/MS) standardized for clinical research. The sensitivity, reproducibility and molecular stability of each targeted metabolite (amino acids, organic acids, acylcarnitines, sugars, bile acids, neurotransmitters, polyamines, and hormones) were assessed under multiple experimental conditions. The metabolic tissue distribution was determined in various rat organs. Furthermore, the method was validated in dry blood spot (DBS) samples collected from patients known to have various inborn errors of metabolism (IEMs). Using this approach, our panel appears to be sensitive and robust as it demonstrated differential and unique metabolic profiles in various rat tissues. Also, as a prospective screening method, this panel of diverse metabolites has the ability to identify patients with a wide range of IEMs who otherwise may need multiple, time-consuming and expensive biochemical assays causing a delay in clinical management. Copyright © 2018 Elsevier B.V. All rights reserved.

National Database for Clinical Trials Related to Mental Illness (NDCT)

Data.gov (United States)

U.S. Department of Health & Human Services — The National Database for Clinical Trials Related to Mental Illness (NDCT) is an extensible informatics platform for relevant data at all levels of biological and...

[Targeting high-risk drugs to optimize clinical pharmacists' intervention].

Science.gov (United States)

Mouterde, Anne-Laure; Bourdelin, Magali; Maison, Ophélie; Coursier, Sandra; Bontemps, Hervé

2016-12-01

By the Order of 6 April 2011, the pharmacist must validate all the prescriptions containing "high-risk drugs" or those of "patients at risk". To optimize this clinical pharmacy activity, we identified high-risk drugs. A list of high-risk drugs has been established using literature, pharmacists' interventions (PI) performed in our hospital and a survey sent to hospital pharmacists. In a prospective study (analysis of 100 prescriptions for each high-risk drug selected), we have identified the most relevant to target. We obtained a statistically significant PI rate (P<0.05) for digoxin, oral anticoagulants direct, oral methotrexate and colchicine. This method of targeted pharmaceutical validation based on high-risk drugs is relevant to detect patients with high risk of medicine-related illness. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Rapid targeted somatic mutation analysis of solid tumors in routine clinical diagnostics.

Science.gov (United States)

Magliacane, Gilda; Grassini, Greta; Bartocci, Paola; Francaviglia, Ilaria; Dal Cin, Elena; Barbieri, Gianluca; Arrigoni, Gianluigi; Pecciarini, Lorenza; Doglioni, Claudio; Cangi, Maria Giulia

2015-10-13

Tumor genotyping is an essential step in routine clinical practice and pathology laboratories face a major challenge in being able to provide rapid, sensitive and updated molecular tests. We developed a novel mass spectrometry multiplexed genotyping platform named PentaPanel to concurrently assess single nucleotide polymorphisms in 56 hotspots of the 5 most clinically relevant cancer genes, KRAS, NRAS, BRAF, EGFR and PIK3CA for a total of 221 detectable mutations. To both evaluate and validate the PentaPanel performance, we investigated 1025 tumor specimens of 6 different cancer types (carcinomas of colon, lung, breast, pancreas, and biliary tract, and melanomas), systematically addressing sensitivity, specificity, and reproducibility of our platform. Sanger sequencing was also performed for all the study samples. Our data showed that PentaPanel is a high throughput and robust tool, allowing genotyping for targeted therapy selection of 10 patients in the same run, with a practical turnaround time of 2 working days. Importantly, it was successfully used to interrogate different DNAs isolated from routinely processed specimens (formalin-fixed paraffin embedded, frozen, and cytological samples), covering all the requirements of clinical tests. In conclusion, the PentaPanel platform can provide an immediate, accurate and cost effective multiplex approach for clinically relevant gene mutation analysis in many solid tumors and its utility across many diseases can be particularly relevant in multiple clinical trials, including the new basket trial approach, aiming to identify appropriate targeted drug combination strategies.

Multimodality molecular imaging - from target description to clinical studies

International Nuclear Information System (INIS)

Schober, O.; Rahbar, K.; Riemann, B.

2009-01-01

This highlight lecture was presented at the closing session of the Annual Congress of the European Association of Nuclear Medicine (EANM) in Munich on 15 October 2008. The Congress was a great success: there were more than 4,000 participants, and 1,597 abstracts were submitted. Of these, 1,387 were accepted for oral or poster presentation, with a rejection rate of 14%. In this article a choice was made from 100 of the 500 lectures which received the highest scores by the scientific review panel. This article outlines the major findings and trends at the EANM 2008, and is only a brief summary of the large number of outstanding abstracts presented. Among the great number of oral and poster presentations covering nearly all fields of nuclear medicine some headlines have to be defined highlighting the development of nuclear medicine in the 21st century. This review focuses on the increasing impact of molecular and multimodality imaging in the field of nuclear medicine. In addition, the question may be asked as to whether the whole spectrum of nuclear medicine is nothing other than molecular imaging and therapy. Furthermore, molecular imaging will and has to go ahead to multimodality imaging. In view of this background the review was structured according to the single steps of molecular imaging, i.e. from target description to clinical studies. The following topics are addressed: targets, radiochemistry and radiopharmacy, devices and computer science, animals and preclinical evaluations, and patients and clinical evaluations. (orig.)

A consensus-based guideline defining clinical target volume for primary disease in external beam radiotherapy for intact uterine cervical cancer

International Nuclear Information System (INIS)

Toita, Takafumi; Ohno, Tatsuya; Kaneyasu, Yuko

2011-01-01

The objective of this study was to develop a consensus-based guideline to define clinical target volume for primary disease (clinical target volume primary) in external beam radiotherapy for intact uterine cervical cancer. The working subgroup of the Japan Clinical Oncology Group (JCOG) Radiation Therapy Study Group began developing a guideline for primary clinical target volume in November 2009. The group consisted of 10 radiation oncologists and 2 gynecologic oncologists. The process started with comparing the contouring on computed tomographic images of actual cervical cancer cases among the members. This was followed by a comprehensive literature review that included primary research articles and textbooks as well as information on surgical procedures. Extensive discussion occurred in face-to-face meetings (three occasions) and frequent e-mail communications until a consensus was reached. The working subgroup reached a consensus on the definition for the clinical target volume primary. The clinical target volume primary consists of the gross tumor volume, uterine cervix, uterine corpus, parametrium, vagina and ovaries. Definitions for these component structures were determined. Anatomical boundaries in all directions were defined for the parametrium. Examples delineating these boundaries were prepared for the posterior border of the parametrium for various clinical situations (id est (i.e.) central tumor bulk, degree of parametrial involvement). A consensus-based guideline defining the clinical target volume primary was developed for external beam radiotherapy for intact uterine cervical cancer. This guideline will serve as a template for radiotherapy protocols in future clinical trials. It may also be used in actual clinical practice in the setting of highly precise external beam radiotherapy, including intensity-modulated radiotherapy. (author)

Use of clinical simulations for patient education: targeting an untapped audience.

Science.gov (United States)

Siwe, Karin; Berterö, Carina; Pugh, Carla; Wijma, Barbro

2009-01-01

In most cases, the health professional has been the target for simulation based learning curricula. We have developed a simulation based curriculum for patient education. In our curriculum lay-women learn how to perform the clinical female pelvic examination using a manikin-based trainer. Learner assessments show that prior negative expectations turned into positive expectations regarding future pelvic examinations.

External audit of clinical practice and medical decision making in a new Asian oncology center: Results and implications for both developing and developed nations

International Nuclear Information System (INIS)

Shakespeare, Thomas P.; Back, Michael F.; Lu, Jiade J.; Lee, Khai Mun; Mukherjee, Rahul K.

2006-01-01

Purpose: The external audit of oncologist clinical practice is increasingly important because of the incorporation of audits into national maintenance of certification (MOC) programs. However, there are few reports of external audits of oncology practice or decision making. Our institution (The Cancer Institute, Singapore) was asked to externally audit an oncology department in a developing Asian nation, providing a unique opportunity to explore the feasibility of such a process. Methods and Materials: We audited 100 randomly selected patients simulated for radiotherapy in 2003, using a previously reported audit instrument assessing clinical documentation/quality assurance and medical decision making. Results: Clinical documentation/quality assurance, decision making, and overall performance criteria were adequate 74.4%, 88.3%, and 80.2% of the time, respectively. Overall 52.0% of cases received suboptimal management. Multivariate analysis revealed palliative intent was associated with improved documentation/clinical quality assurance (p = 0.07), decision making (p 0.007), overall performance (p = 0.003), and optimal treatment rates (p 0.07); non-small-cell lung cancer or central nervous system primary sites were associated with better decision making (p = 0.001), overall performance (p = 0.03), and optimal treatment rates (p = 0.002). Conclusions: Despite the poor results, the external audit had several benefits. It identified learning needs for future targeting, and the auditor provided facilitating feedback to address systematic errors identified. Our experience was also helpful in refining our national revalidation audit instrument. The feasibility of the external audit supports the consideration of including audit in national MOC programs

HaloPlex Targeted Resequencing for Mutation Detection in Clinical Formalin-Fixed, Paraffin-Embedded Tumor Samples.

Science.gov (United States)

Moens, Lotte N J; Falk-Sörqvist, Elin; Ljungström, Viktor; Mattsson, Johanna; Sundström, Magnus; La Fleur, Linnéa; Mathot, Lucy; Micke, Patrick; Nilsson, Mats; Botling, Johan

2015-11-01

In recent years, the advent of massively parallel next-generation sequencing technologies has enabled substantial advances in the study of human diseases. Combined with targeted DNA enrichment methods, high sequence coverage can be obtained for different genes simultaneously at a reduced cost per sample, creating unique opportunities for clinical cancer diagnostics. However, the formalin-fixed, paraffin-embedded (FFPE) process of tissue samples, routinely used in pathology departments, results in DNA fragmentation and nucleotide modifications that introduce a number of technical challenges for downstream biomolecular analyses. We evaluated the HaloPlex target enrichment system for somatic mutation detection in 80 tissue fractions derived from 20 clinical cancer cases with paired tumor and normal tissue available in both FFPE and fresh-frozen format. Several modifications to the standard method were introduced, including a reduced target fragment length and two strand capturing. We found that FFPE material can be used for HaloPlex-based target enrichment and next-generation sequencing, even when starting from small amounts of DNA. By specifically capturing both strands for each target fragment, we were able to reduce the number of false-positive errors caused by FFPE-induced artifacts and lower the detection limit for somatic mutations. We believe that the HaloPlex method presented here will be broadly applicable as a tool for somatic mutation detection in clinical cancer settings. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Real-time non-rigid target tracking for ultrasound-guided clinical interventions

Science.gov (United States)

Zachiu, C.; Ries, M.; Ramaekers, P.; Guey, J.-L.; Moonen, C. T. W.; de Senneville, B. Denis

2017-10-01

Biological motion is a problem for non- or mini-invasive interventions when conducted in mobile/deformable organs due to the targeted pathology moving/deforming with the organ. This may lead to high miss rates and/or incomplete treatment of the pathology. Therefore, real-time tracking of the target anatomy during the intervention would be beneficial for such applications. Since the aforementioned interventions are often conducted under B-mode ultrasound (US) guidance, target tracking can be achieved via image registration, by comparing the acquired US images to a separate image established as positional reference. However, such US images are intrinsically altered by speckle noise, introducing incoherent gray-level intensity variations. This may prove problematic for existing intensity-based registration methods. In the current study we address US-based target tracking by employing the recently proposed EVolution registration algorithm. The method is, by construction, robust to transient gray-level intensities. Instead of directly matching image intensities, EVolution aligns similar contrast patterns in the images. Moreover, the displacement is computed by evaluating a matching criterion for image sub-regions rather than on a point-by-point basis, which typically provides more robust motion estimates. However, unlike similar previously published approaches, which assume rigid displacements in the image sub-regions, the EVolution algorithm integrates the matching criterion in a global functional, allowing the estimation of an elastic dense deformation. The approach was validated for soft tissue tracking under free-breathing conditions on the abdomen of seven healthy volunteers. Contact echography was performed on all volunteers, while three of the volunteers also underwent standoff echography. Each of the two modalities is predominantly specific to a particular type of non- or mini-invasive clinical intervention. The method demonstrated on average an accuracy of�

Reducing US cardiovascular disease burden and disparities through national and targeted dietary policies: A modelling study.

Directory of Open Access Journals (Sweden)

Jonathan Pearson-Stuttard

2017-06-01

Full Text Available Large socio-economic disparities exist in US dietary habits and cardiovascular disease (CVD mortality. While economic incentives have demonstrated success in improving dietary choices, the quantitative impact of different dietary policies on CVD disparities is not well established. We aimed to quantify and compare the potential effects on total CVD mortality and disparities of specific dietary policies to increase fruit and vegetable (F&V consumption and reduce sugar-sweetened beverage (SSB consumption in the US.Using the US IMPACT Food Policy Model and probabilistic sensitivity analyses, we estimated and compared the reductions in CVD mortality and socio-economic disparities in the US population potentially achievable from 2015 to 2030 with specific dietary policy scenarios: (a a national mass media campaign (MMC aimed to increase consumption of F&Vs and reduce consumption of SSBs, (b a national fiscal policy to tax SSBs to increase prices by 10%, (c a national fiscal policy to subsidise F&Vs to reduce prices by 10%, and (d a targeted policy to subsidise F&Vs to reduce prices by 30% among Supplemental Nutrition Assistance Program (SNAP participants only. We also evaluated a combined policy approach, combining all of the above policies. Data sources included the Surveillance, Epidemiology, and End Results Program, National Vital Statistics System, National Health and Nutrition Examination Survey, and published meta-analyses. Among the individual policy scenarios, a national 10% F&V subsidy was projected to be most beneficial, potentially resulting in approximately 150,500 (95% uncertainty interval [UI] 141,400-158,500 CVD deaths prevented or postponed (DPPs by 2030 in the US. This far exceeds the approximately 35,100 (95% UI 31,700-37,500 DPPs potentially attributable to a 30% F&V subsidy targeting SNAP participants, the approximately 25,800 (95% UI 24,300-28,500 DPPs for a 1-y MMC, or the approximately 31,000 (95% UI 26,800-35,300 DPPs for a 10

Design of a deuterium and tritium-ablator shock ignition target for the National Ignition Facility

International Nuclear Information System (INIS)

Terry, Matthew R.; Perkins, L. John; Sepke, Scott M.

2012-01-01

Shock ignition presents a viable path to ignition and high gain on the National Ignition Facility (NIF). In this paper, we describe the development of the 1D design of 0.5 MJ class, all-deuterium and tritium (fuel and ablator) shock ignition target that should be reasonably robust to Rayleigh-Taylor fluid instabilities, mistiming, and hot electron preheat. The target assumes “day one” NIF hardware and produces a yield of 31 MJ with reasonable allowances for laser backscatter, absorption efficiency, and polar drive power variation. The energetics of polar drive laser absorption require a beam configuration with half of the NIF quads dedicated to launching the ignitor shock, while the remaining quads drive the target compression. Hydrodynamic scaling of the target suggests that gains of 75 and yields 70 MJ may be possible.

A national survey of memory clinics in the Republic of Ireland.

Science.gov (United States)

Cahill, Suzanne; Pierce, Maria; Moore, Vanessa

2014-04-01

This national survey investigates the location, resourcing, staff composition, treatments, waiting time, and numbers of patients attending memory clinics (MCs) in the Republic of Ireland. It also explores Directors' attitudes to future service development including their views about the advantages and disadvantages of quality standards for MCs. An audio-taped telephone interview was conducted with the Directors. A total of 14 MCs were identified across the Republic of Ireland, ten of which are hospital-based and most of which offer diagnostic services and are located in Dublin. Nine MCs are medical consultant led and operate under the direction of either Old Age Psychiatrists or Geriatricians. Results show wide variation regarding the location, team size, service availability, and numbers of patients attending. The average number of patients attending in 2011 was 126. Only six clinics employ dedicated Allied Health Professionals. Less than half of the clinics are research active. Whilst most Directors welcomed the availability of national standards, several expressed concern that standards might, in the absence of funding, result in the closure of the most poorly resourced services. This survey provides valuable data on the main characteristics of all of the 14 MCs delivering services in the Republic of Ireland and raises critical and fundamental questions about the goals and outcomes of MC services. The survey data collected can be used by other countries for cross-national comparison.

Polyimide capsules may hold high pressure DT fuel without cryogenic support for the National Ignition Facility indirect-drive targets

International Nuclear Information System (INIS)

Sanchez, J.J.; Letts, S.A.

1997-01-01

New target designs for the Omega upgrade laser and ignition targets in the National Ignition Facility (NIF) require thick (80 - 100 microm) cryogenic fuel layers. The Omega upgrade target will require cryogenic handling after initial fill because of the high fill pressures and the thin capsule walls. For the NIF indirectly driven targets, a larger capsule size and new materials offer hope that they can be built, filled and stored in a manner similar to the targets used in the Nova facility without requiring cryogenic handling

Similar clinical benefits from below-target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial.

Science.gov (United States)

Lam, Phillip H; Dooley, Daniel J; Fonarow, Gregg C; Butler, Javed; Bhatt, Deepak L; Filippatos, Gerasimos S; Deedwania, Prakash; Forman, Daniel E; White, Michel; Fletcher, Ross D; Arundel, Cherinne; Blackman, Marc R; Adamopoulos, Chris; Kanonidis, Ioannis E; Aban, Inmaculada B; Patel, Kanan; Aronow, Wilbert S; Allman, Richard M; Anker, Stefan D; Pitt, Bertram; Ahmed, Ali

2018-02-01

To examine associations of below-target and target dose of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, with outcomes in patients with heart failure and reduced ejection fraction (HFrEF) in the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial. Two thousand five hundred and sixty-nine patients with HFrEF (ejection fraction ≤35%) were randomized to below-target (5-10 mg/day) dose placebo (n = 1284) or enalapril (n = 1285). One month post-randomization, blind up-titration to target (20 mg/day) dose was attempted for both study drugs in 2458 patients. Among the 1444 patients who achieved dose up-titration (placebo, n = 748; enalapril, n = 696; mean dose for both groups, 20.0 mg/day), target dose enalapril (vs. target dose placebo) was associated with a 9% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality [adjusted hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.60-0.81; P target dose (placebo, n = 486; enalapril, n = 528; mean dose for both groups, 8.8 mg/day), below-target dose enalapril (vs. below-target dose placebo) was associated with a 12% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 0.68; 95% CI 0.57-0.81; P target (vs. below-target) dose had no association with the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 1.04; 95% CI 0.87-1.23; P = 0.695). In patients with HFrEF, the clinical benefits of ACE inhibitors appear to be similar at both below-target and target doses. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

How is feedback from national clinical audits used? Views from English National Health Service trust audit leads.

Science.gov (United States)

Taylor, Angelina; Neuburger, Jenny; Walker, Kate; Cromwell, David; Groene, Oliver

2016-04-01

To explore how the output of national clinical audits in England is used by professionals and whether and how their impact could be enhanced. A mixed-methods study with the primary recipients of four national clinical audits of cancer care of 607 local audit leads, 274 (45%) completed a questionnaire and 32 participated in an interview. Our questions focused on how the audits were used and whether barriers existed to using the audits for local service improvement. We described variation in questionnaire responses between the audits using chi-squared tests. Results are reported as percentages with their 95% confidence intervals. Qualitative data were analysed using Framework analysis. More than 90% of survey respondents believed that the audit findings were relevant to their clinical work, and interviewees described how they used the audits for a range of purposes. Forty-two percent of survey respondents said they had changed their clinical practice, and 56% had implemented service improvements in response to the audits. The degree of change differed between the four audits, evident in both the questionnaire and the interview data. In the interviews, two recurring barriers emerged: (1) the importance of data quality, which, in turn, influenced the perceived relevance and validity of the audit data and therefore the ability to make changes based on it and (2) the need for clear presentation of benchmarked local performance data. The perceived authority and credibility of the professional bodies supporting the audits was a key factor underpinning the use of the audit findings. National cancer audit and feedback is used to improve services, but their impact could be enhanced by improving the data quality and relevance of feedback. © The Author(s) 2016.

Prevention of hepatocellular carcinoma: potential targets, experimental models, and clinical challenges

Science.gov (United States)

Hoshida, Yujin; Fuchs, Bryan C.; Tanabe, Kenneth K.

2013-01-01

Chronic fibrotic liver diseases such as viral hepatitis eventually develop liver cirrhosis, which causes occurrence of hepatocellular carcinoma (HCC). Given the limited therapeutic efficacy in advanced HCC, prevention of HCC development could be an effective strategy for improving patient prognosis. However, there is still no established therapy to meet the goal. Studies have elucidated a wide variety of molecular mechanisms and signaling pathways involved in HCC development. Genetically-engineered or chemically-treated experimental models of cirrhosis and HCC have been developed and shown their potential value in investigating molecular therapeutic targets and diagnostic biomarkers for HCC prevention. In this review, we overview potential targets of prevention and currently available experimental models, and discuss strategies to translate the findings into clinical practice. PMID:22873223

Recommendations for Clinical Pathology Data Generation, Interpretation, and Reporting in Target Animal Safety Studies for Veterinary Drug Development.

Science.gov (United States)

Siska, William; Gupta, Aradhana; Tomlinson, Lindsay; Tripathi, Niraj; von Beust, Barbara

Clinical pathology testing is routinely performed in target animal safety studies in order to identify potential toxicity associated with administration of an investigational veterinary pharmaceutical product. Regulatory and other testing guidelines that address such studies provide recommendations for clinical pathology testing but occasionally contain outdated analytes and do not take into account interspecies physiologic differences that affect the practical selection of appropriate clinical pathology tests. Additionally, strong emphasis is often placed on statistical analysis and use of reference intervals for interpretation of test article-related clinical pathology changes, with limited attention given to the critical scientific review of clinically, toxicologically, or biologically relevant changes. The purpose of this communication from the Regulatory Affairs Committee of the American Society for Veterinary Clinical Pathology is to provide current recommendations for clinical pathology testing and data interpretation in target animal safety studies and thereby enhance the value of clinical pathology testing in these studies.

MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis.

Science.gov (United States)

Kasivisvanathan, Veeru; Rannikko, Antti S; Borghi, Marcelo; Panebianco, Valeria; Mynderse, Lance A; Vaarala, Markku H; Briganti, Alberto; Budäus, Lars; Hellawell, Giles; Hindley, Richard G; Roobol, Monique J; Eggener, Scott; Ghei, Maneesh; Villers, Arnauld; Bladou, Franck; Villeirs, Geert M; Virdi, Jaspal; Boxler, Silvan; Robert, Grégoire; Singh, Paras B; Venderink, Wulphert; Hadaschik, Boris A; Ruffion, Alain; Hu, Jim C; Margolis, Daniel; Crouzet, Sébastien; Klotz, Laurence; Taneja, Samir S; Pinto, Peter; Gill, Inderbir; Allen, Clare; Giganti, Francesco; Freeman, Alex; Morris, Stephen; Punwani, Shonit; Williams, Norman R; Brew-Graves, Chris; Deeks, Jonathan; Takwoingi, Yemisi; Emberton, Mark; Moore, Caroline M

2018-05-10

Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; Pprostate cancer who had not undergone biopsy previously. (Funded by the National Institute for

Clinical efficacy of local targeted chemotherapy for triple-negative breast cancer

International Nuclear Information System (INIS)

He, Jinsong; Wang, Xianming; Guan, Hong; Chen, Weicai; Wang, Ming; Wu, Huisheng; Wang, Zun; Zhou, Ruming; Qiu, Shuibo

2011-01-01

The aim of the study was to evaluate the clinical efficacy of superselective intra-arterial targeted neo-adjuvant chemotherapy in the treatment of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)-negative (triple-negative) breast cancer. A total of 47 triple-negative breast cancer patients (29 at stage II, 13 at stage III and 5 at stage IV) were randomly assigned to two groups: targeted chemotherapy group (n=24) and control group (n=23). Patients in the targeted chemotherapy group received preoperative superselective intra-arterial chemotherapy with CEF regimen (C: cyclophosphamide [600 mg/m 2 ]; E: epirubicin [90 mg/m 2 ]; F: 5-fluorouracil [600 mg/m 2 ]), and those in the control group received routine neoadjuvant chemotherapy with CEF. The duration of the treatment, changes in lesions and the prognosis were determined. The average course of the treatment was 15 days in the targeted chemotherapy group which was significantly shorter than that in the control group (31 days) (P<0.01). The remission rate of lesions was 91.6% in the targeted chemotherapy group and 60.9% in the control group, respectively. Among these patients, 9 died within two years, including 2 (both at IV stage) in the targeted chemotherapy group and 7 (2 at stage II, 4 at stage III and 1 at stage IV) in the control group. As an neoadjuvant therapy, the superselective intra-arterial chemotherapy is effective for triple-negative breast cancer, with advantages of the short treatment course and favourable remission rates as well as prognoses

Visualization of target inspection data at the National Ignition Facility

Energy Technology Data Exchange (ETDEWEB)

Potter, Daniel, E-mail: potter15@llnl.gov [Lawrence Livermore National Laboratory (United States); Antipa, Nick, E-mail: antipa1@llnl.gov [Lawrence Livermore National Laboratory (United States)

2012-12-15

Highlights: Black-Right-Pointing-Pointer Target surfaces are measured using a phase-shifting diffraction interferometer. Black-Right-Pointing-Pointer Datasets are several gigabytes that consist of tens to hundreds of files. Black-Right-Pointing-Pointer Software tools that provide a high-level overview of the entire dataset. Black-Right-Pointing-Pointer Single datasets loaded into the visualization session can be individually rotated. Black-Right-Pointing-Pointer Multiple datasets with common features are found then datasets can be aligned. - Abstract: As the National Ignition Facility continues its campaign to achieve ignition, new methods and tools will be required to measure the quality of the target capsules used to achieve this goal. Techniques have been developed to measure capsule surface features using a phase-shifting diffraction interferometer and Leica Microsystems confocal microscope. These instruments produce multi-gigabyte datasets which consist of tens to hundreds of files. Existing software can handle viewing a small subset of an entire dataset, but none can view a dataset in its entirety. Additionally, without an established mode of transport that keeps the target capsules properly aligned throughout the assembly process, a means of aligning the two dataset coordinate systems is needed. The goal of this project is to develop web based software utilizing WebGL which will provide high level overview visualization of an entire dataset, with the capability to retrieve finer details on demand, in addition to facilitating alignment of multiple datasets with one another based on common features that have been visually identified by users of the system.

Anomalies in target-controlled infusion: an analysis after 20 years of clinical use.

Science.gov (United States)

Engbers, F H M; Dahan, A

2018-05-01

Although target-controlled infusion has been in use for more than two decades, its benefits are being obscured by anomalies in clinical practice caused by a number of important problems. These include: a variety of pharmacokinetic models available in open target-controlled infusion systems, which often confuse the user; the extrapolation of anthropomorphic data which provokes anomalous adjustments of dosing by such systems; and the uncertainty of regulatory requirements for the application of target-controlled infusion which causes uncontrolled exploitation of drugs and pharmacokinetic models in target-controlled infusion devices. Comparison of performance of pharmacokinetic models is complex and mostly inconclusive. However, a specific behaviour of a model in a target-controlled infusion system that is neither intended nor supported by scientific data can be considered an artefact or anomaly. Several of these anomalies can be identified in the current commercially available target-controlled infusion systems and are discussed in this review. © 2018 The Association of Anaesthetists of Great Britain and Ireland.

Clinical validation of targeted next-generation sequencing for inherited disorders.

Science.gov (United States)

Yohe, Sophia; Hauge, Adam; Bunjer, Kari; Kemmer, Teresa; Bower, Matthew; Schomaker, Matthew; Onsongo, Getiria; Wilson, Jon; Erdmann, Jesse; Zhou, Yi; Deshpande, Archana; Spears, Michael D; Beckman, Kenneth; Silverstein, Kevin A T; Thyagarajan, Bharat

2015-02-01

Although next-generation sequencing (NGS) can revolutionize molecular diagnostics, several hurdles remain in the implementation of this technology in clinical laboratories. To validate and implement an NGS panel for genetic diagnosis of more than 100 inherited diseases, such as neurologic conditions, congenital hearing loss and eye disorders, developmental disorders, nonmalignant diseases treated by hematopoietic cell transplantation, familial cancers, connective tissue disorders, metabolic disorders, disorders of sexual development, and cardiac disorders. The diagnostic gene panels ranged from 1 to 54 genes with most of panels containing 10 genes or fewer. We used a liquid hybridization-based, target-enrichment strategy to enrich 10 067 exons in 568 genes, followed by NGS with a HiSeq 2000 sequencing system (Illumina, San Diego, California). We successfully sequenced 97.6% (9825 of 10 067) of the targeted exons to obtain a minimum coverage of 20× at all bases. We demonstrated 100% concordance in detecting 19 pathogenic single-nucleotide variations and 11 pathogenic insertion-deletion mutations ranging in size from 1 to 18 base pairs across 18 samples that were previously characterized by Sanger sequencing. Using 4 pairs of blinded, duplicate samples, we demonstrated a high degree of concordance (>99%) among the blinded, duplicate pairs. We have successfully demonstrated the feasibility of using the NGS platform to multiplex genetic tests for several rare diseases and the use of cloud computing for bioinformatics analysis as a relatively low-cost solution for implementing NGS in clinical laboratories.

Resource implications of a national health target

DEFF Research Database (Denmark)

Jones, Peter; Sopina, Liza Elizaveta; Ashton, Toni

2014-01-01

Background The Shorter Stays in Emergency Departments health target was introduced in New Zealand in 2009. District Health Boards (DHBs) are expected to meet the target with no additional funding or incentives. The costs of implementing such targets have not previously been studied. Method A survey.......03), whereas expenditure in the hospital was not (r = 0.08, P = 0.75). Conclusion The fact that estimated expenditure on the target was over $50 million without additional funding suggests that DHBs were able to make savings through improved efficiencies and/or that funds were reallocated from other services...

Status and methodology of publicly available national HIV care continua and 90-90-90 targets: A systematic review.

Directory of Open Access Journals (Sweden)

Reuben Granich

2017-04-01

Full Text Available In 2014, the Joint United Nations Program on HIV/AIDS (UNAIDS issued treatment goals for human immunodeficiency virus (HIV. The 90-90-90 target specifies that by 2020, 90% of individuals living with HIV will know their HIV status, 90% of people with diagnosed HIV infection will receive antiretroviral treatment (ART, and 90% of those taking ART will be virally suppressed. Consistent methods and routine reporting in the public domain will be necessary for tracking progress towards the 90-90-90 target.For the period 2010-2016, we searched PubMed, UNAIDS country progress reports, World Health Organization (WHO, UNAIDS reports, national surveillance and program reports, United States President's Emergency Plan for AIDS Relief (PEPFAR Country Operational Plans, and conference presentations and/or abstracts for the latest available national HIV care continuum in the public domain. Continua of care included the number and proportion of people living with HIV (PLHIV who are diagnosed, on ART, and virally suppressed out of the estimated number of PLHIV. We ranked the described methods for indicators to derive high-, medium-, and low-quality continuum. For 2010-2016, we identified 53 national care continua with viral suppression estimates representing 19.7 million (54% of the 2015 global estimate of PLHIV. Of the 53, 6 (with 2% of global burden were high quality, using standard surveillance methods to derive an overall denominator and program data from national cohorts for estimating steps in the continuum. Only nine countries in sub-Saharan Africa had care continua with viral suppression estimates. Of the 53 countries, the average proportion of the aggregate of PLHIV from all countries on ART was 48%, and the proportion of PLHIV who were virally suppressed was 40%. Seven countries (Sweden, Cambodia, United Kingdom, Switzerland, Denmark, Rwanda, and Namibia were within 12% and 10% of achieving the 90-90-90 target for "on ART" and for "viral suppression

Antibodies to autoantigen targets in myasthenia and their value in clinical practice

Directory of Open Access Journals (Sweden)

S. I. Dedaev

2014-01-01

Full Text Available Myasthenia gravis is a classic autoimmune disease, which clinical manifestations in the form of weakness and abnormal muscle fatigue, due to the damaging effect of polyclonal antibodies to different structures of the neuromuscular synapse and muscles. The study of autoimmune substrate with myasthenia is routine in many clinics dealing with the problems of neuromuscular pathology, and the identification of high concentration of serum antibodies to a number of antigenic structures is the gold standard in diagnosis.Determination of serum antibodies to various autoimmune targets is an important tool in clinical practice. The majority of patients shows the high concentration of antibodies to AchR that gives the opportunity to use it as an important diagnostic criterion. The specificity of changes in the concentration of AchR-antibodies due to pathogenetic treatment allows to objectify the suppression of autoimmune aggression and evaluate the reliability of remission. However, the absence of AchR-antibodies when there are clear clinical and electromyography signs of myasthenia gravis suggests an autoimmune attack against a number of other targets, the most studied of which is the MuSK. On the contrary, patients with myasthenia gravis associated with thymoma, almost always have a higher level of AchR-antibodies. The presence of thymoma is accompanied by the generation of antibodies to titin and RyR, which is also observed in persons with late-onset myasthenia without thymoma. High concentration of antibodies to these structures can be interpreted as a reliable sign of thymoma in patients younger than 60 years.

Framework for the analysis of the low-carbon scenario 2020 to achieve the national carbon Emissions reduction target: Focused on educational facilities

International Nuclear Information System (INIS)

Koo, Choongwan; Kim, Hyunjoong; Hong, Taehoon

2014-01-01

Since the increase in greenhouse gas emissions has increased the global warming potential, an international agreement on carbon emissions reduction target (CERT) has been formulated in Kyoto Protocol (1997). This study aimed to develop a framework for the analysis of the low-carbon scenario 2020 to achieve the national CERT. To verify the feasibility of the proposed framework, educational facilities were used for a case study. This study was conducted in six steps: (i) selection of the target school; (ii) establishment of the reference model for the target school; (iii) energy consumption pattern analysis by target school; (iv) establishment of the energy retrofit model for the target school; (v) economic and environmental assessment through the life cycle cost and life cycle CO 2 analysis; and (vi) establishment of the low-carbon scenario in 2020 to achieve the national CERT. This study can help facility managers or policymakers establish the optimal retrofit strategy within the limited budget from a short-term perspective and the low-carbon scenario 2020 to achieve the national CERT from the long-term perspective. The proposed framework could be also applied to any other building type or country in the global environment

A 21st Century National Public Health System

Science.gov (United States)

2008-09-01

Security (DHS) released fifteen national planning scenarios in 2004 and the Target Capabilities List: A Companion to the National Preparedness Goal in...no clinical samples available from the first SARS patient in China to test for the virus; however, the second identified SARS case was a chef , Huang...Xingchu, who worked at a restaurant and was reported to have atypical pneumonia. As a chef , he came into regular contact with several types of

A Miniaturized Chemical Proteomic Approach for Target Profiling of Clinical Kinase Inhibitors in Tumor Biopsies

Science.gov (United States)

Chamrád, Ivo; Rix, Uwe; Stukalov, Alexey; Gridling, Manuela; Parapatics, Katja; Müller, André C.; Altiok, Soner; Colinge, Jacques; Superti-Furga, Giulio; Haura, Eric B.; Bennett, Keiryn L.

2014-01-01

While targeted therapy based on the idea of attenuating the activity of a preselected, therapeutically relevant protein has become one of the major trends in modern cancer therapy, no truly specific targeted drug has been developed and most clinical agents have displayed a degree of polypharmacology. Therefore, the specificity of anticancer therapeutics has emerged as a highly important but severely underestimated issue. Chemical proteomics is a powerful technique combining postgenomic drug-affinity chromatography with high-end mass spectrometry analysis and bioinformatic data processing to assemble a target profile of a desired therapeutic molecule. Due to high demands on the starting material, however, chemical proteomic studies have been mostly limited to cancer cell lines. Herein, we report a down-scaling of the technique to enable the analysis of very low abundance samples, as those obtained from needle biopsies. By a systematic investigation of several important parameters in pull-downs with the multikinase inhibitor bosutinib, the standard experimental protocol was optimized to 100 µg protein input. At this level, more than 30 well-known targets were detected per single pull-down replicate with high reproducibility. Moreover, as presented by the comprehensive target profile obtained from miniaturized pull-downs with another clinical drug, dasatinib, the optimized protocol seems to be extendable to other drugs of interest. Sixty distinct human and murine targets were finally identified for bosutinib and dasatinib in chemical proteomic experiments utilizing core needle biopsy samples from xenotransplants derived from patient tumor tissue. Altogether, the developed methodology proves robust and generic and holds many promises for the field of personalized health care. PMID:23901793

The first target experiments on the National Ignition Facility

International Nuclear Information System (INIS)

Landen, O.L.; Glenzer, S.H.; Froula, D.H.; Dewald, E.L.; Suter, L.J.; Schneider, M.B.; Hinkel, D.E.; Fernandez, J.C.; Kline, J.L.; Goldman, S.R.; Braun, D.G.; Celliers, P.M.; Moon, S.J.; Robey, H.S.; Lanier, N.E.; Glendinning, S.G.; Blue, B.E.; Wilde, B.H.; Jones, O.S.; Schein, J.; Divol, L.; Kalantar, D.H.; Campbell, K.M.; Holder, J.P.; McDonald, J.W.; Niemann, C.; Mackinnon, A.J.; Collins, G.W.; Bradley, D.K.; Eggert, J.H.; Hicks, D.G.; Gregori, G.; Kirkwood, R.K.; Young, B.K.; Foster, J.M.; Hansen, J.F.; Perry, T.S.; Munro, D.H.; Baldis, H.A.; Grim, G.P.; Heeter, R.F.; Hegelich, M.B.; Montgomery, D.S.; Rochau, G.A.; Olson, R.E.; Turner, R.E.; Workman, J.B.; Berger, R.L.; Cohen, B.I.; Kruer, W.L.; Langdon, A.B.; Langer, S.H.; Meezan, N.B.; Rose, H.A.; Still, C.H.; Williams, E.A.; Dodd, E.A.; Edwards, M.J.; Monteil, M.C.; Stevenson, R.M.; Thomas, B.R.; Coker, R.F.; Magelssen, G.R.; Rosen, P.A.; Stry, P.E.; Woods, D.; Weber, S.V.; Young, P.E.; Alvarez, S.; Armstrong, G.; Bahr, R.; Bourgade, G.L.; Bower, D.; Celeste, J.; Chrisp, M.; Compton, S.; Cox, J.; Constantin, C.; Costa, R.; Duncan, J.; Ellis, A.; Emig, J.; Gautier, C.; Greenwood, A.; Griffith, R.; Holdner, F.; Holtmeier, G.; Hargrove, D.; James, T.; Kamperschroer, J.; Kimbrough, J.; Landon, M.; Lee, F.D.; Malone, R.; May, M.; Montelongo, S.; Moody, J.; Ng, E.; Nikitin, A.; Pellinen, D.; Piston, K.; Poole, M.; Rekow, V.; Rhodes, M.; Shepherd, R.; Shiromizu, S.; Voloshin, D.; Warrick, A.; Watts, P.; Weber, F.; Young, P.; Arnold, P.

2007-01-01

A first set of shock timing, laser-plasma interaction, hohlraum energetics and hydrodynamic experiments have been performed using the first 4 beams of the National Ignition Facility (NIF), in support of indirect drive Inertial Confinement Fusion (ICF) and High Energy Density Physics (HEDP). In parallel, a robust set of optical and X-ray spectrometers, interferometer, calorimeters and imagers have been activated. The experiments have been undertaken with laser powers and energies of up to 8 TW and 17 kJ in flattop and shaped 1-9 ns pulses focused with various beam smoothing options. The experiments have demonstrated excellent agreement between measured and predicted laser-target coupling in foils and hohlraums, even when extended to a longer pulse regime unattainable at previous laser facilities, validated the predicted effects of beam smoothing on intense laser beam propagation in long scale-length plasmas and begun to test 3-dimensional codes by extending the study of laser driven hydrodynamic jets to 3-dimensional geometries. (authors)

The first target experiments on the National Ignition Facility

Energy Technology Data Exchange (ETDEWEB)

Landen, O.L.; Glenzer, S.H.; Froula, D.H.; Dewald, E.L.; Suter, L.J.; Schneider, M.B.; Hinkel, D.E.; Fernandez, J.C.; Kline, J.L.; Goldman, S.R.; Braun, D.G.; Celliers, P.M.; Moon, S.J.; Robey, H.S.; Lanier, N.E.; Glendinning, S.G.; Blue, B.E.; Wilde, B.H.; Jones, O.S.; Schein, J.; Divol, L.; Kalantar, D.H.; Campbell, K.M.; Holder, J.P.; McDonald, J.W.; Niemann, C.; Mackinnon, A.J.; Collins, G.W.; Bradley, D.K.; Eggert, J.H.; Hicks, D.G.; Gregori, G.; Kirkwood, R.K.; Young, B.K.; Foster, J.M.; Hansen, J.F.; Perry, T.S.; Munro, D.H.; Baldis, H.A.; Grim, G.P.; Heeter, R.F.; Hegelich, M.B.; Montgomery, D.S.; Rochau, G.A.; Olson, R.E.; Turner, R.E.; Workman, J.B.; Berger, R.L.; Cohen, B.I.; Kruer, W.L.; Langdon, A.B.; Langer, S.H.; Meezan, N.B.; Rose, H.A.; Still, C.H.; Williams, E.A.; Dodd, E.A.; Edwards, M.J.; Monteil, M.C.; Stevenson, R.M.; Thomas, B.R.; Coker, R.F.; Magelssen, G.R.; Rosen, P.A.; Stry, P.E.; Woods, D.; Weber, S.V.; Young, P.E.; Alvarez, S.; Armstrong, G.; Bahr, R.; Bourgade, G.L.; Bower, D.; Celeste, J.; Chrisp, M.; Compton, S.; Cox, J.; Constantin, C.; Costa, R.; Duncan, J.; Ellis, A.; Emig, J.; Gautier, C.; Greenwood, A.; Griffith, R.; Holdner, F.; Holtmeier, G.; Hargrove, D.; James, T.; Kamperschroer, J.; Kimbrough, J.; Landon, M.; Lee, F.D.; Malone, R.; May, M.; Montelongo, S.; Moody, J.; Ng, E.; Nikitin, A.; Pellinen, D.; Piston, K.; Poole, M.; Rekow, V.; Rhodes, M.; Shepherd, R.; Shiromizu, S.; Voloshin, D.; Warrick, A.; Watts, P.; Weber, F.; Young, P.; Arnold, P

2007-08-15

A first set of shock timing, laser-plasma interaction, hohlraum energetics and hydrodynamic experiments have been performed using the first 4 beams of the National Ignition Facility (NIF), in support of indirect drive Inertial Confinement Fusion (ICF) and High Energy Density Physics (HEDP). In parallel, a robust set of optical and X-ray spectrometers, interferometer, calorimeters and imagers have been activated. The experiments have been undertaken with laser powers and energies of up to 8 TW and 17 kJ in flattop and shaped 1-9 ns pulses focused with various beam smoothing options. The experiments have demonstrated excellent agreement between measured and predicted laser-target coupling in foils and hohlraums, even when extended to a longer pulse regime unattainable at previous laser facilities, validated the predicted effects of beam smoothing on intense laser beam propagation in long scale-length plasmas and begun to test 3-dimensional codes by extending the study of laser driven hydrodynamic jets to 3-dimensional geometries. (authors)

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in clinical practice

DEFF Research Database (Denmark)

Sturgeon, Catharine M; Hoffman, Barry R; Chan, Daniel W

2008-01-01

BACKGROUND: This report presents updated National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines summarizing quality requirements for the use of tumor markers. METHODS: One subcommittee developed guidelines for analytical quality relevant to serum and tissue-based tumor...... questions to ensure selection of the appropriate test, adherence to good clinical and laboratory practices (e.g., minimization of the risk of incorrect patient and/or specimen identification, tube type, or timing), use of internationally standardized and well-characterized methods, careful adherence...... records. Also mandatory is extensive validation encompassing all stages of analysis before introduction of new technologies such as microarrays and mass spectrometry. Provision of high-quality tumor marker services is facilitated by dialogue involving researchers, diagnostic companies, clinical...

Experience of targeted Usher exome sequencing as a clinical test

Science.gov (United States)

Besnard, Thomas; García-García, Gema; Baux, David; Vaché, Christel; Faugère, Valérie; Larrieu, Lise; Léonard, Susana; Millan, Jose M; Malcolm, Sue; Claustres, Mireille; Roux, Anne-Françoise

2014-01-01

We show that massively parallel targeted sequencing of 19 genes provides a new and reliable strategy for molecular diagnosis of Usher syndrome (USH) and nonsyndromic deafness, particularly appropriate for these disorders characterized by a high clinical and genetic heterogeneity and a complex structure of several of the genes involved. A series of 71 patients including Usher patients previously screened by Sanger sequencing plus newly referred patients was studied. Ninety-eight percent of the variants previously identified by Sanger sequencing were found by next-generation sequencing (NGS). NGS proved to be efficient as it offers analysis of all relevant genes which is laborious to reach with Sanger sequencing. Among the 13 newly referred Usher patients, both mutations in the same gene were identified in 77% of cases (10 patients) and one candidate pathogenic variant in two additional patients. This work can be considered as pilot for implementing NGS for genetically heterogeneous diseases in clinical service. PMID:24498627

Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies

Science.gov (United States)

2017-10-01

prostate cancer . Cancer Res 70: 7992-8002, 2010 8. Nelson PS: Molecular states underlying an- drogen receptor activation: A framework for thera- peutics...targeting androgen signaling in prostate cancer . J Clin Oncol 30:644-646, 2012 9. Thadani-Mulero M, Nanus DM, Giannakakou P: Androgen receptor on the... prostate cancer . Clin Cancer Res 21:795-807, 2015 17. van Soest RJ, de Morrée ES, Kweldam CF, et al: Targeting the androgen receptor confers in vivo

Patients with advanced and metastatic renal cell carcinoma treated with targeted therapy in the Czech Republic: twenty cancer centres, six agents, one database.

Science.gov (United States)

Poprach, Alexandr; Bortlíček, Zbyněk; Büchler, Tomáš; Melichar, Bohuslav; Lakomý, Radek; Vyzula, Rostislav; Brabec, Petr; Svoboda, Marek; Dušek, Ladislav; Gregor, Jakub

2012-12-01

The incidence and mortality of renal cell carcinoma (RCC) in the Czech Republic are among the highest in the world. Several targeted agents have been recently approved for the treatment of advanced/metastatic RCC. Presentation of a national clinical database for monitoring and assessment of patients with advanced/metastatic RCC treated with targeted therapy. The RenIS (RENal Information System, http://renis.registry.cz ) registry is a non-interventional post-registration database of epidemiological and clinical data of patients with RCC treated with targeted therapies in the Czech Republic. Twenty cancer centres eligible for targeted therapy administration participate in the project. As of November 2011, six agents were approved and reimbursed from public health insurance, including bevacizumab, everolimus, pazopanib, sorafenib, sunitinib, and temsirolimus. As of 10 October 2011, 1,541 patients with valid records were entered into the database. Comparison with population-based data from the Czech National Cancer Registry revealed that RCC patients treated with targeted therapy are significantly younger (median age at diagnosis 59 vs. 66 years). Most RenIS registry patients were treated with sorafenib and sunitinib, many patients sequentially with both agents. Over 10 % of patients were also treated with everolimus in the second or third line. Progression-free survival times achieved were comparable to phase III clinical trials. The RenIS registry has become an important tool and source of information for the management of cancer care and clinical practice, providing comprehensive data on monitoring and assessment of RCC targeted therapy on a national level.

A novel clinically translatable fluorescent nanoparticle for targeted molecular imaging of tumors in living subjects.

Science.gov (United States)

Gao, Jinhao; Chen, Kai; Luong, Richard; Bouley, Donna M; Mao, Hua; Qiao, Tiecheng; Gambhir, Sanjiv S; Cheng, Zhen

2012-01-11

The use of quantum dots (QDs) in biomedical research has grown tremendously, yet successful examples of clinical applications are absent due to many clinical concerns. Here, we report on a new type of stable and biocompatible dendron-coated InP/ZnS core/shell QD as a clinically translatable nanoprobe for molecular imaging applications. The QDs (QD710-Dendron) were demonstrated to hold several significant features: near-infrared (NIR) emission, high stability in biological media, suitable size with possible renal clearance, and ability of extravasation. More importantly, a pilot mouse toxicity study confirmed that QD710-Dendron lacks significant toxicity at the doses tested. The acute tumor uptake of QD710-Dendron resulted in good contrast from the surrounding nontumorous tissues, indicating the possibility of passive targeting of the QDs. The highly specific targeting of QD710-Dendron-RGD(2) to integrin α(v)β(3)-positive tumor cells resulted in high tumor uptake and long retention of the nanoprobe at tumor sites. In summary, QD710-Dendron and RGD-modified nanoparticles demonstrate small size, high stability, biocompatibility, favorable in vivo pharmacokinetics, and successful tumor imaging properties. These features satisfy the requirements for clinical translation and should promote efforts to further investigate the possibility of using QD710-Dendron-based nanoprobes in the clinical setting in the near future. © 2011 American Chemical Society

panelcn.MOPS: Copy-number detection in targeted NGS panel data for clinical diagnostics.

Science.gov (United States)

Povysil, Gundula; Tzika, Antigoni; Vogt, Julia; Haunschmid, Verena; Messiaen, Ludwine; Zschocke, Johannes; Klambauer, Günter; Hochreiter, Sepp; Wimmer, Katharina

2017-07-01

Targeted next-generation-sequencing (NGS) panels have largely replaced Sanger sequencing in clinical diagnostics. They allow for the detection of copy-number variations (CNVs) in addition to single-nucleotide variants and small insertions/deletions. However, existing computational CNV detection methods have shortcomings regarding accuracy, quality control (QC), incidental findings, and user-friendliness. We developed panelcn.MOPS, a novel pipeline for detecting CNVs in targeted NGS panel data. Using data from 180 samples, we compared panelcn.MOPS with five state-of-the-art methods. With panelcn.MOPS leading the field, most methods achieved comparably high accuracy. panelcn.MOPS reliably detected CNVs ranging in size from part of a region of interest (ROI), to whole genes, which may comprise all ROIs investigated in a given sample. The latter is enabled by analyzing reads from all ROIs of the panel, but presenting results exclusively for user-selected genes, thus avoiding incidental findings. Additionally, panelcn.MOPS offers QC criteria not only for samples, but also for individual ROIs within a sample, which increases the confidence in called CNVs. panelcn.MOPS is freely available both as R package and standalone software with graphical user interface that is easy to use for clinical geneticists without any programming experience. panelcn.MOPS combines high sensitivity and specificity with user-friendliness rendering it highly suitable for routine clinical diagnostics. © 2017 The Authors. Human Mutation published by Wiley Periodicals, Inc.

THE NATIONAL ONCOLOGICAL PROGRAM IMPLEMENTATION – EXPERIENCE IN THE VLADIMIR REGION (TO THE 70TH ANNIVERSARY OF THE REGIONAL CLINICAL ONCOLOGICAL DISPENSARY

Directory of Open Access Journals (Sweden)

A. G. Zirin

2017-01-01

Full Text Available By 2010, on the background of the steady increase in the incidence of malignant tumors in the Vladimir area, primary oncological care level worked inefficiently.Condition of material and technical base of the Vladimir Regional Clinical Oncological Dispensary was also unsatisfactory. All these problems required solution in the form of the National Oncology Program realization in the region. The National Oncological Program has begun to work in the Vladimir region since 2011. Target indicators of the oncological program implementation by 2015 were established. They are: Increase of 5-year survival value of patients with malignant tumors after diagnosis date to 51.4%; Increase the number of malignant tumors early detection cases at the I–II stages up to 51%; Decrease the mortality rate of working age population to 99 per 100 000; Decrease of mortality within one year from the first time of cancer diagnosis to 27%. The following main objectives such as radically improved the material and technical base of oncology dispensary; modern methods of prevention, diagnosis and patients treatment improvement and introduction; the system providing population cancer care focused on the cancer early detection and the specialized combined antitumor treatment provision are realized in order to achieve these goals. The implementation of the tasks allowed to achieve positive dynamics of Vladimir region population cancer care indicators. All the main targets of the National Oncology Program for the Vladimir region were achieved successfully. Implementation of the National Oncology Program has had an extremely positive effect on the cancer services development of, as well as for the health of the entire population of the Vladimir region.

Profiling cancer gene mutations in clinical formalin-fixed, paraffin-embedded colorectal tumor specimens using targeted next-generation sequencing.

Science.gov (United States)

Zhang, Liangxuan; Chen, Liangjing; Sah, Sachin; Latham, Gary J; Patel, Rajesh; Song, Qinghua; Koeppen, Hartmut; Tam, Rachel; Schleifman, Erica; Mashhedi, Haider; Chalasani, Sreedevi; Fu, Ling; Sumiyoshi, Teiko; Raja, Rajiv; Forrest, William; Hampton, Garret M; Lackner, Mark R; Hegde, Priti; Jia, Shidong

2014-04-01

The success of precision oncology relies on accurate and sensitive molecular profiling. The Ion AmpliSeq Cancer Panel, a targeted enrichment method for next-generation sequencing (NGS) using the Ion Torrent platform, provides a fast, easy, and cost-effective sequencing workflow for detecting genomic "hotspot" regions that are frequently mutated in human cancer genes. Most recently, the U.K. has launched the AmpliSeq sequencing test in its National Health Service. This study aimed to evaluate the clinical application of the AmpliSeq methodology. We used 10 ng of genomic DNA from formalin-fixed, paraffin-embedded human colorectal cancer (CRC) tumor specimens to sequence 46 cancer genes using the AmpliSeq platform. In a validation study, we developed an orthogonal NGS-based resequencing approach (SimpliSeq) to assess the AmpliSeq variant calls. Validated mutational analyses revealed that AmpliSeq was effective in profiling gene mutations, and that the method correctly pinpointed "true-positive" gene mutations with variant frequency >5% and demonstrated high-level molecular heterogeneity in CRC. However, AmpliSeq enrichment and NGS also produced several recurrent "false-positive" calls in clinically druggable oncogenes such as PIK3CA. AmpliSeq provided highly sensitive and quantitative mutation detection for most of the genes on its cancer panel using limited DNA quantities from formalin-fixed, paraffin-embedded samples. For those genes with recurrent "false-positive" variant calls, caution should be used in data interpretation, and orthogonal verification of mutations is recommended for clinical decision making.

Tau-Centric Targets and Drugs in Clinical Development for the Treatment of Alzheimer’s Disease

Directory of Open Access Journals (Sweden)

Francesco Panza

2016-01-01

Full Text Available The failure of several Phase II/III clinical trials in Alzheimer’s disease (AD with drugs targeting β-amyloid accumulation in the brain fuelled an increasing interest in alternative treatments against tau pathology, including approaches targeting tau phosphatases/kinases, active and passive immunization, and anti-tau aggregation. The most advanced tau aggregation inhibitor (TAI is methylthioninium (MT, a drug existing in equilibrium between a reduced (leuco-methylthioninium and oxidized form (MT+. MT chloride (methylene blue was investigated in a 24-week Phase II clinical trial in 321 patients with mild to moderate AD that failed to show significant positive effects in mild AD patients, although long-term observations (50 weeks and biomarker studies suggested possible benefit. The dose of 138 mg/day showed potential benefits on cognitive performance of moderately affected AD patients and cerebral blood flow in mildly affected patients. Further clinical evidence will come from the large ongoing Phase III trials for the treatment of AD and the behavioral variant of frontotemporal dementia on a new form of this TAI, more bioavailable and less toxic at higher doses, called TRx0237. More recently, inhibitors of tau acetylation are being actively pursued based on impressive results in animal studies obtained by salsalate, a clinically used derivative of salicylic acid.

Evaluation of Peritumoral Edema in the Delineation of Radiotherapy Clinical Target Volumes for Glioblastoma

International Nuclear Information System (INIS)

Chang, Eric L.; Akyurek, Serap; Avalos, Tedde C; Rebueno, Neal C; Spicer, Chris C; Garcia, John C; Famiglietti, Robin; Allen, Pamela K.; Chao, K.S. Clifford; Mahajan, Anita; Woo, Shiao Y.; Maor, Moshe H.

2007-01-01

Purpose: To evaluate the spatial relationship between peritumoral edema and recurrence pattern in patients with glioblastoma (GBM). Methods and Materials: Forty-eight primary GBM patients received three-dimensional conformal radiotherapy that did not intentionally include peritumoral edema within the clinical target volume between July 2000 and June 2001. All 48 patients have subsequently recurred, and their original treatment planning parameters were used for this study. New theoretical radiation treatment plans were created for the same 48 patients, based on Radiation Therapy Oncology Group (RTOG) target delineation guidelines that specify inclusion of peritumoral edema. Target volume and recurrent tumor coverage, as well as percent volume of normal brain irradiated, were assessed for both methods of target delineation using dose-volume histograms. Results: A comparison between the location of recurrent tumor and peritumoral edema volumes from all 48 cases failed to show correlation by linear regression modeling (r 2 0.0007; p = 0.3). For patients with edema >75 cm 3 , the percent volume of brain irradiated to 46 Gy was significantly greater in treatment plans that intentionally included peritumoral edema compared with those that did not (38% vs. 31%; p = 0.003). The pattern of failure was identical between the two sets of plans (40 central, 3 in-field, 3 marginal, and 2 distant recurrence). Conclusion: Clinical target volume delineation based on a 2-cm margin rather than on peritumoral edema did not seem to alter the central pattern of failure for patients with GBM. For patients with peritumoral edema >75 cm 3 , using a constant 2-cm margin resulted in a smaller median percent volume of brain being irradiated to 30 Gy, 46 Gy, and 50 Gy compared with corresponding theoretical RTOG plans that deliberately included peritumoral edema

Reformulation of a clinical-dose system for carbon-ion radiotherapy treatment planning at the National Institute of Radiological Sciences, Japan

Science.gov (United States)

Inaniwa, Taku; Kanematsu, Nobuyuki; Matsufuji, Naruhiro; Kanai, Tatsuaki; Shirai, Toshiyuki; Noda, Koji; Tsuji, Hiroshi; Kamada, Tadashi; Tsujii, Hirohiko

2015-04-01

At the National Institute of Radiological Sciences (NIRS), more than 8,000 patients have been treated for various tumors with carbon-ion (C-ion) radiotherapy in the past 20 years based on a radiobiologically defined clinical-dose system. Through clinical experience, including extensive dose escalation studies, optimum dose-fractionation protocols have been established for respective tumors, which may be considered as the standards in C-ion radiotherapy. Although the therapeutic appropriateness of the clinical-dose system has been widely demonstrated by clinical results, the system incorporates several oversimplifications such as dose-independent relative biological effectiveness (RBE), empirical nuclear fragmentation model, and use of dose-averaged linear energy transfer to represent the spectrum of particles. We took the opportunity to update the clinical-dose system at the time we started clinical treatment with pencil beam scanning, a new beam delivery method, in 2011. The requirements for the updated system were to correct the oversimplifications made in the original system, while harmonizing with the original system to maintain the established dose-fractionation protocols. In the updated system, the radiation quality of the therapeutic C-ion beam was derived with Monte Carlo simulations, and its biological effectiveness was predicted with a theoretical model. We selected the most used C-ion beam with αr = 0.764 Gy-1 and β = 0.0615 Gy-2 as reference radiation for RBE. The C-equivalent biological dose distribution is designed to allow the prescribed survival of tumor cells of the human salivary gland (HSG) in entire spread-out Bragg peak (SOBP) region, with consideration to the dose dependence of the RBE. This C-equivalent biological dose distribution is scaled to a clinical dose distribution to harmonize with our clinical experiences with C-ion radiotherapy. Treatment plans were made with the original and the updated clinical-dose systems, and both

Target volume definition for external beam partial breast radiotherapy: Clinical, pathological and technical studies informing current approaches

International Nuclear Information System (INIS)

Kirby, Anna M.; Coles, Charlotte E.; Yarnold, John R.

2010-01-01

Partial breast irradiation (PBI) is currently under investigation in several phase III trials and, following a recent consensus statement, its use off-study may increase despite ongoing uncertainty regarding optimal target volume definition. We review the clinical, pathological and technical evidence for target volume definition in external beam partial breast irradiation (EB-PBI). The optimal method of tumour bed (TB) delineation requires X-ray CT imaging of implanted excision cavity wall markers. The definition of clinical target volume (CTV) as TB plus concentric 15 mm margins is based on the anatomical distribution of multifocal and multicentric disease around the primary tumour in mastectomy specimens, and the clinical locations of local tumour relapse (LR) after breast conservation surgery. If the majority of LR originate from foci of residual invasive and/or intraduct disease in the vicinity of the TB after complete microscopic resection, CTV margin logically takes account of the position of primary tumour within the surgical resection specimen. The uncertain significance of independent primary tumours as sources of preventable LR, and of wound healing responses in stimulating LR, increases the difficulties in defining optimal CTV. These uncertainties may resolve after long-term follow-up of current PBI trials. By contrast, a commonly used 10 mm clinical to planning target volume (PTV) margin has a stronger evidence base, although departmental set-up errors need to be confirmed locally. A CTV-PTV margin >10 mm may be required in women with larger breasts and/or large seromas, whilst the role of image-guided radiotherapy with or without TB markers in reducing CTV-PTV margins needs to be explored.

A National Strategy to Develop Pragmatic Clinical Trials Infrastructure

Science.gov (United States)

Guise, Jeanne‐Marie; Dolor, Rowena J.; Meissner, Paul; Tunis, Sean; Krishnan, Jerry A.; Pace, Wilson D.; Saltz, Joel; Hersh, William R.; Michener, Lloyd; Carey, Timothy S.

2014-01-01

Abstract An important challenge in comparative effectiveness research is the lack of infrastructure to support pragmatic clinical trials, which compare interventions in usual practice settings and subjects. These trials present challenges that differ from those of classical efficacy trials, which are conducted under ideal circumstances, in patients selected for their suitability, and with highly controlled protocols. In 2012, we launched a 1‐year learning network to identify high‐priority pragmatic clinical trials and to deploy research infrastructure through the NIH Clinical and Translational Science Awards Consortium that could be used to launch and sustain them. The network and infrastructure were initiated as a learning ground and shared resource for investigators and communities interested in developing pragmatic clinical trials. We followed a three‐stage process of developing the network, prioritizing proposed trials, and implementing learning exercises that culminated in a 1‐day network meeting at the end of the year. The year‐long project resulted in five recommendations related to developing the network, enhancing community engagement, addressing regulatory challenges, advancing information technology, and developing research methods. The recommendations can be implemented within 24 months and are designed to lead toward a sustained national infrastructure for pragmatic trials. PMID:24472114

Individual-level outcomes from a national clinical leadership development programme.

Science.gov (United States)

Patton, Declan; Fealy, Gerard; McNamara, Martin; Casey, Mary; Connor, Tom O; Doyle, Louise; Quinlan, Christina

2013-08-01

A national clinical leadership development programme was instituted for Irish nurses and midwives in 2010. Incorporating a development framework and leadership pathway and a range of bespoke interventions for leadership development, including workshops, action-learning sets, mentoring and coaching, the programme was introduced at seven pilot sites in the second half of 2011. The programme pilot was evaluated with reference to structure, process and outcomes elements, including individual-level programme outcomes. Evaluation data were generated through focus groups and group interviews, individual interviews and written submissions. The data provided evidence of nurses' and midwives' clinical leadership development through self and observer-reported behaviours and dispositions including accounts of how the programme participants developed and displayed particular clinical leadership competencies. A key strength of the new programme was that it involved interventions that focussed on specific leadership competencies to be developed within the practice context.

National survey of pain clinics in Croatia: Organization and services.

Science.gov (United States)

Fidahić, Mahir; Dogan, Katarina; Sapunar, Damir; Puljak, Livia

2015-01-01

To analyze organization and therapeutic procedures administered in tertiary outpatient pain clinics in Croatia. Data about organization of pain clinics, its personnel, equipment, continuing medical education, therapeutic procedures, research activities and relations with pharmaceutical industry were collected using questionnaires. Twenty-two Croatian pain clinics were included in the study. Most of the pain clinics employ exclusively anesthesiologists and nurses. The most frequently prescribed therapeutic procedures in pain clinics were pharmacotherapy, transcutaneous electrical nerve stimulation, acupuncture and trigger point injections. Almost all pain clinics provide educational material for patients. Most of the pain clinics have regular interactions with pharmaceutical companies. Prescribing decisions were based mostly on information from scientific meetings, research articles and consultations with colleagues. Information sources which are considered to be the gold standard--the systematic reviews of The Cochrane Collaboration--were used less frequently (n=12; 57%) than advertising materials from pharmaceutical companies (n=16; 76%). Few physicians and other pain clinics staff had scientific degrees or academic titles or were involved in a research project. The national study about pain clinics in Croatia pointed out that there is room for improvement of their organization and services. Pain clinics should employ health-care professionals with diverse backgrounds. They should offer treatments backed by the highest-level of scientific evidence. Since pain is a major public health issue, pain clinic staff should engage more in research to contribute to the growing field of pain research, to enhance capacities for pain research in Croatia, to incorporate scientific evidence into their daily decision-making and to enable evidence-based practice. Copyright © 2015 by Academy of Sciences and Arts of Bosnia and Herzegovina.

National survey of pain clinics in Croatia: Organization and services

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Mahir Fidahić

2015-05-01

Full Text Available Objective. To analyze organization and therapeutic procedures administered in tertiary outpatient pain clinics in Croatia. Methods. Data about organization of pain clinics, its personnel, equipment, continuing medical education, therapeutic procedures, research activities and relations with pharmaceutical industry were collected using questionnaires. Results. Twenty-two Croatian pain clinics were included in the study. Most of the pain clinics employ exclusively anesthesiologists and nurses. The most frequently prescribed therapeutic procedures in pain clinics were pharmacotherapy, transcutaneous electrical nerve stimulation, acupuncture and trigger point injections. Almost all pain clinics provide educational material for patients. Most of the pain clinics have regular interactions with pharmaceutical companies. Prescribing decisions were based mostly on information from scientific meetings, research articles and consultations with colleagues. Information sources which are considered to be the gold standard – the systematic reviews of The Cochrane Collaboration – were used less frequently (n=12; 57% than advertising materials from pharmaceutical companies (n=16; 76%. Few physicians and other pain clinics staff had scientific degrees or academic titles or were involved in a research project. Conclusion. The national study about pain clinics in Croatia pointed out that there is room for improvement of their organization and services. Pain clinics should employ health-care professionals with diverse backgrounds. They should offer treatments backed by the highest-level of scientific evidence. Since pain is a major public health issue, pain clinic staff should engage more in research to contribute to the growing field of pain research, to enhance capacities for pain research in Croatia, to incorporate scientific evidence into their daily decision-making and to enable evidence-based practice.

A Criticality Safety Study on Storing Unirradiated Cintichem-Type Targets at Sandia National Laboratories

International Nuclear Information System (INIS)

Romero, D.J.; Parma, E.J.; Busch, R.D.

1999-01-01

This criticality safety analysis is performed to determine the effective multiplication factor (k eff ) for a storage cabinet filled with unirradiated Cintichem-type targets. These targets will be used to produce 99 Mo at Sandia National Laboratories and will be stored on-site prior to irradiation in the Annular Core Research Reactor. The analysis consisted of using the Monte Carlo code MCNP (Version 4A) to model and predict the k eff for the proposed dry storage configuration under credible loss of geometry and moderator control. Effects of target pitch, non-uniform loading, and target internal/external flooding are evaluated. Further studies were done with deterministic methods to verify the results obtained from MCNP and to obtain a clearer understanding of the parameters affecting system criticality. The diffusion accelerated neutral particle transport code ONEDANT was used to model the target in a one-dimensional, infinite half-slab geometry and determine the critical slab thickness. Hand calculations were also completed to determine the critical slab thickness with modified one-group, and one-group, two region approximations. Results obtained from ONEDANT and the hand calculations were compared to applicable cases in a commonly used criticality safety analysis handbook. Overall, the critical slab thicknesses obtained in the deterministic analysis were much larger than the dimensions of the cabinet and further support the predictions by MCNP that a critical system cannot be attained for the base case or in conditions where loss of geometry and moderation control occur

Small Molecule Sequential Dual-Targeting Theragnostic Strategy (SMSDTTS): from Preclinical Experiments towards Possible Clinical Anticancer Applications.

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Li, Junjie; Oyen, Raymond; Verbruggen, Alfons; Ni, Yicheng

2013-01-01

Hitting the evasive tumor cells proves challenging in targeted cancer therapies. A general and unconventional anticancer approach namely small molecule sequential dual-targeting theragnostic strategy (SMSDTTS) has recently been introduced with the aims to target and debulk the tumor mass, wipe out the residual tumor cells, and meanwhile enable cancer detectability. This dual targeting approach works in two steps for systemic delivery of two naturally derived drugs. First, an anti-tubulin vascular disrupting agent, e.g., combretastatin A4 phosphate (CA4P), is injected to selectively cut off tumor blood supply and to cause massive necrosis, which nevertheless always leaves peripheral tumor residues. Secondly, a necrosis-avid radiopharmaceutical, namely (131)I-hypericin ((131)I-Hyp), is administered the next day, which accumulates in intratumoral necrosis and irradiates the residual cancer cells with beta particles. Theoretically, this complementary targeted approach may biologically and radioactively ablate solid tumors and reduce the risk of local recurrence, remote metastases, and thus cancer mortality. Meanwhile, the emitted gamma rays facilitate radio-scintigraphy to detect tumors and follow up the therapy, hence a simultaneous theragnostic approach. SMSDTTS has now shown promise from multicenter animal experiments and may demonstrate unique anticancer efficacy in upcoming preliminary clinical trials. In this short review article, information about the two involved agents, the rationale of SMSDTTS, its preclinical antitumor efficacy, multifocal targetability, simultaneous theragnostic property, and toxicities of the dose regimens are summarized. Meanwhile, possible drawbacks, practical challenges and future improvement with SMSDTTS are discussed, which hopefully may help to push forward this strategy from preclinical experiments towards possible clinical applications.

The relation between societal factors and different forms of prejudice: A cross-national approach on target-specific and generalized prejudice.

Science.gov (United States)

Meeusen, Cecil; Kern, Anna

2016-01-01

The goal of this paper was to investigate the generalizability of prejudice across contexts by analyzing associations between different types of prejudice in a cross-national perspective and by investigating the relation between country-specific contextual factors and target-specific prejudices. Relying on the European Social Survey (2008), results indicated that prejudices were indeed positively associated, confirming the existence of a generalized prejudice component. Next to substantial cross-national differences in associational strength, also within country variance in target-specific associations was observed. This suggested that the motivations for prejudice largely vary according to the intergroup context. Two aspects of the intergroup context - economic conditions and cultural values - showed to be related to generalized and target-specific components of prejudice. Future research on prejudice and context should take an integrative approach that considers both the idea of generalized and specific prejudice simultaneously. Copyright © 2015 Elsevier Inc. All rights reserved.

Federated queries of clinical data repositories: Scaling to a national network.

Science.gov (United States)

Weber, Griffin M

2015-06-01

Federated networks of clinical research data repositories are rapidly growing in size from a handful of sites to true national networks with more than 100 hospitals. This study creates a conceptual framework for predicting how various properties of these systems will scale as they continue to expand. Starting with actual data from Harvard's four-site Shared Health Research Information Network (SHRINE), the framework is used to imagine a future 4000 site network, representing the majority of hospitals in the United States. From this it becomes clear that several common assumptions of small networks fail to scale to a national level, such as all sites being online at all times or containing data from the same date range. On the other hand, a large network enables researchers to select subsets of sites that are most appropriate for particular research questions. Developers of federated clinical data networks should be aware of how the properties of these networks change at different scales and design their software accordingly. Copyright © 2015 Elsevier Inc. All rights reserved.

Nighttime assaults: using a national emergency department monitoring system to predict occurrence, target prevention and plan services

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Bellis Mark A

2012-09-01

Full Text Available Abstract Background Emergency department (ED data have the potential to provide critical intelligence on when violence is most likely to occur and the characteristics of those who suffer the greatest health impacts. We use a national experimental ED monitoring system to examine how it could target violence prevention interventions towards at risk communities and optimise acute responses to calendar, holiday and other celebration-related changes in nighttime assaults. Methods A cross-sectional examination of nighttime assault presentations (6.01 pm to 6.00 am; n = 330,172 over a three-year period (31st March 2008 to 30th March 2011 to English EDs analysing changes by weekday, month, holidays, major sporting events, and demographics of those presenting. Results Males are at greater risk of assault presentation (adjusted odds ratio [AOR] 3.14, 95% confidence intervals [CIs] 3.11-3.16; P 2 = 0.918; P  Conclusions To date, the role of ED data has focused on helping target nightlife police activity. Its utility is much greater; capable of targeting and evaluating multi-agency life course approaches to violence prevention and optimising frontline resources. National ED data are critical for fully engaging health services in the prevention of violence.

Targeted drugs for pulmonary arterial hypertension: a network meta-analysis of 32 randomized clinical trials

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Gao XF

2017-05-01

Full Text Available Xiao-Fei Gao,1 Jun-Jie Zhang,1,2 Xiao-Min Jiang,1 Zhen Ge,1,2 Zhi-Mei Wang,1 Bing Li,1 Wen-Xing Mao,1 Shao-Liang Chen1,2 1Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 2Department of Cardiology, Nanjing Heart Center, Nanjing, People’s Republic of China Background: Pulmonary arterial hypertension (PAH is a devastating disease and ultimately leads to right heart failure and premature death. A total of four classical targeted drugs, prostanoids, endothelin receptor antagonists (ERAs, phosphodiesterase 5 inhibitors (PDE-5Is, and soluble guanylate cyclase stimulator (sGCS, have been proved to improve exercise capacity and hemodynamics compared to placebo; however, direct head-to-head comparisons of these drugs are lacking. This network meta-analysis was conducted to comprehensively compare the efficacy of these targeted drugs for PAH.Methods: Medline, the Cochrane Library, and other Internet sources were searched for randomized clinical trials exploring the efficacy of targeted drugs for patients with PAH. The primary effective end point of this network meta-analysis was a 6-minute walk distance (6MWD.Results: Thirty-two eligible trials including 6,758 patients were identified. There was a statistically significant improvement in 6MWD, mean pulmonary arterial pressure, pulmonary vascular resistance, and clinical worsening events associated with each of the four targeted drugs compared with placebo. Combination therapy improved 6MWD by 20.94 m (95% confidence interval [CI]: 6.94, 34.94; P=0.003 vs prostanoids, and 16.94 m (95% CI: 4.41, 29.47; P=0.008 vs ERAs. PDE-5Is improved 6MWD by 17.28 m (95% CI: 1.91, 32.65; P=0.028 vs prostanoids, with a similar result with combination therapy. In addition, combination therapy reduced mean pulmonary artery pressure by 3.97 mmHg (95% CI: -6.06, -1.88; P<0.001 vs prostanoids, 8.24 mmHg (95% CI: -10.71, -5.76; P<0.001 vs ERAs, 3.38 mmHg (95% CI: -6.30, -0.47; P=0.023 vs

XML-based clinical data standardisation in the National Health Service Scotland

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Raluca Bunduchi

2006-12-01

Full Text Available The objective of this paper is to clarify the role that socio-economic factors played in shaping the development of XML-based clinical data standards in the National Health Service in Scotland from 2000 to 2004. The paper discusses the NHS Scotland approach to clinical data standardisation, emphasising the actors involved, their choices during the standard development process and the factors that have shaped these choices. The case suggests that the NHS Scotland approach to clinical data standardisation is shaped by strong political pressures for fast development of an integrated electronic patient care system, economic pressures for high efficiency and cost reductions, and organisational requirements for strong clinical support. Such economic, political and organisational pressures explain the informal approach to standard development, the emphasis on fast system development and strong clinical involvement. At the same time, market factors explain the low commitment of the IT vendors, which might have otherwise put significant pressure onNHSScotland to pursue a more formalised standardisation approach within an internationally recognised standard-setting body.

Current Molecular Targeted Therapy in Advanced Gastric Cancer: A Comprehensive Review of Therapeutic Mechanism, Clinical Trials, and Practical Application

Directory of Open Access Journals (Sweden)

Kaichun Li

2016-01-01

Full Text Available Despite the great progress in the treatment of gastric cancer, it is still the third leading cause of cancer death worldwide. Patients often miss the opportunity for a surgical cure, because the cancer has already developed into advanced cancer when identified. Compared to best supportive care, chemotherapy can improve quality of life and prolong survival time, but the overall survival is often short. Due to the molecular study of gastric cancer, new molecular targeted drugs have entered the clinical use. Trastuzumab, an antibody targeting human epidermal growth factor receptor 2 (HER2, can significantly improve survival in advanced gastric cancer patients with HER2 overexpression. Second-line treatment of advanced gastric cancer with ramucirumab, an antibody targeting VEGFR-2, alone or in combination with paclitaxel, has been proved to provide a beneficial effect. The VEGFR-2 tyrosine kinase inhibitor, apatinib, can improve the survival of advanced gastric cancer patients after second-line chemotherapy failure. Unfortunately, none of the EGFR targeting antibodies (cetuximab or panitumumab, VEGF targeting monoclonal antibodies (bevacizumab, mTOR inhibitor (everolimus, or HGF/MET pathway targeting drugs has a significant survival benefit. Many other clinical trials based on molecular markers are underway. This review will summarize targeted therapies for advanced gastric cancer.

Clinical efficacy and management of monoclonal antibodies targeting CD38 and SLAMF7 in multiple myeloma

DEFF Research Database (Denmark)

van de Donk, Niels W C J; Moreau, Philippe; Plesner, Torben

2016-01-01

Immunotherapeutic strategies are emerging as promising therapeutic approaches in multiple myeloma (MM), with several monoclonal antibodies in advanced stages of clinical development. Of these agents, CD38-targeting antibodies have marked single agent activity in extensively pretreated MM...... of therapeutic antibodies with immunofixation and serum protein electrophoresis assays may lead to underestimation of complete response. Strategies to mitigate interference, based on shifting the therapeutic antibody band, are in development. Furthermore, daratumumab, and probably also other CD38-targeting...

Heterogeneity in head and neck IMRT target design and clinical practice

International Nuclear Information System (INIS)

Hong, Theodore S.; Tomé, Wolfgang A.; Harari, Paul M.

2012-01-01

Purpose: To assess patterns of H and N IMRT practice with particular emphasis on elective target delineation. Materials and methods: Twenty institutions with established H and N IMRT expertise were solicited to design clinical target volumes for the identical H and N cancer case. To limit contouring variability, a primary tonsil GTV and ipsilateral level II node were pre-contoured. Participants were asked to accept this GTV, and contour their recommended CTV and PTV. Dose prescriptions, contouring time, and recommendations regarding chemotherapy were solicited. Results: All 20 institutions responded. Remarkable heterogeneity in H and N IMRT design and practice was identified. Seventeen of 20 centers recommended treatment of bilateral necks whereas 3/20 recommended treatment of the ipsilateral neck only. The average CTV volume was 250 cm 3 (range 37–676 cm 3 ). Although there was high concordance in coverage of ipsilateral neck levels II and III, substantial variation was identified for levels I, V, and the contralateral neck. Average CTV expansion was 4.1 mm (range 0–15 mm). Eight of 20 centers recommended chemotherapy (cisplatin), whereas 12/20 recommended radiation alone. Responders prescribed on average 69 and 68 Gy to the tumor and metastatic node GTV, respectively. Average H and N target volume contouring time was 102.5 min (range 60–210 min). Conclusion: This study identifies substantial heterogeneity in H and N IMRT target definition, prescription, neck treatment, and use of chemotherapy among practitioners with established H and N IMRT expertise. These data suggest that continued efforts to standardize and simplify the H and N IMRT process are desirable for the safe and effective global advancement of H and N IMRT practice.

Subsidies to target specialist outreach services into more remote locations: a national cross-sectional study.

Science.gov (United States)

O'Sullivan, Belinda G; McGrail, Matthew R; Stoelwinder, Johannes U

2017-07-01

Objective Targeting rural outreach services to areas of highest relative need is challenging because of the higher costs it imposes on health workers to travel longer distances. This paper studied whether subsidies have the potential to support the provision of specialist outreach services into more remote locations. Methods National data about subsidies for medical specialist outreach providers as part of the Wave 7 Medicine in Australia: Balancing Employment and Life (MABEL) Survey in 2014. Results Nearly half received subsidies: 19% (n=110) from a formal policy, namely the Australian Government Rural Health Outreach Fund (RHOF), and 27% (n=154) from other sources. Subsidised specialists travelled for longer and visited more remote locations relative to the non-subsidised group. In addition, compared with non-subsidised specialists, RHOF-subsidised specialists worked in priority areas and provided equally regular services they intended to continue, despite visiting more remote locations. Conclusion This suggests the RHOF, although limited to one in five specialist outreach providers, is important to increase targeted and stable outreach services in areas of highest relative need. Other subsidies also play a role in facilitating remote service distribution, but may need to be more structured to promote regular, sustained outreach practice. What is known about this topic? There are no studies describing subsidies for specialist doctors to undertake rural outreach work and whether subsidies, including formal and structured subsidies via the Australian Government RHOF, support targeted outreach services compared with no financial support. What does this paper add? Using national data from Australia, we describe subsidisation among specialist outreach providers and show that specialists subsidised via the RHOF or another source are more likely to provide remote outreach services. What are the implications for practitioners? Subsidised specialist outreach providers are

Image-aided Suicide Gene Therapy Utilizing Multifunctional hTERT-targeting Adenovirus for Clinical Translation in Hepatocellular Carcinoma.

Science.gov (United States)

Kim, Yun-Hee; Kim, Kyung Tae; Lee, Sang-Jin; Hong, Seung-Hee; Moon, Ju Young; Yoon, Eun Kyung; Kim, Sukyoung; Kim, Eun Ok; Kang, Se Hun; Kim, Seok Ki; Choi, Sun Il; Goh, Sung Ho; Kim, Daehong; Lee, Seong-Wook; Ju, Mi Ha; Jeong, Jin Sook; Kim, In-Hoo

2016-01-01

Trans-splicing ribozyme enables to sense and reprogram target RNA into therapeutic transgene and thereby becomes a good sensing device for detection of cancer cells, judging from transgene expression. Previously we proposed PEPCK-Rz-HSVtk (PRT), hTERT targeting trans-splicing ribozyme (Rz) driven by liver-specific promoter phosphoenolpyruvate carboxykinase (PEPCK) with downstream suicide gene, herpes simplex virus thymidine kinase (HSVtk) for hepatocellular carcinoma (HCC) gene therapy. Here, we describe success of a re-engineered adenoviral vector harboring PRT in obtaining greater antitumor activity with less off-target effect for clinical application as a theranostics. We introduced liver-selective apolipoprotein E (ApoE) enhancer to the distal region of PRT unit to augment activity and liver selectivity of PEPCK promoter, and achieved better transduction into liver cancer cells by replacement of serotype 35 fiber knob on additional E4orf1-4 deletion of E1&E3-deleted serotype 5 back bone. We demonstrated that our refined adenovirus harboring PEPCK/ApoE-Rz-HSVtk (Ad-PRT-E) achieved great anti-tumor efficacy and improved ability to specifically target HCC without damaging normal hepatocytes. We also showed noninvasive imaging modalities were successfully employed to monitor both how well a therapeutic gene (HSVtk) was expressed inside tumor and how effectively a gene therapy took an action in terms of tumor growth. Collectively, this study suggests that the advanced therapeutic adenoviruses Ad-PRT-E and its image-aided evaluation system may lead to the powerful strategy for successful clinical translation and the development of clinical protocols for HCC therapy.

A consensus-based guideline defining the clinical target volume for pelvic lymph nodes in external beam radiotherapy for uterine cervical cancer

International Nuclear Information System (INIS)

Toita, Takafumi; Ohno, Tatsuya; Kaneyasu, Yuko

2010-01-01

The objective of this study was to develop a consensus-based guideline as well as an atlas defining pelvic nodal clinical target volumes in external beam radiotherapy for uterine cervical cancer. A working subgroup to establish the consensus-based guideline on clinical target volumes for uterine cervical cancer was formulated by the Radiation Therapy Study Group of the Japan Clinical Oncology Group in July 2008. The working subgroup consisted of seven radiation oncologists. The process resulting in the consensus included a comparison of contouring on CT images among the members, reviewing of published textbooks and the relevant literature and a distribution analysis of metastatic nodes on computed tomography/magnetic resonance imaging of actual patients. The working subgroup defined the pelvic nodal clinical target volumes for cervical cancer and developed an associated atlas. As a basic criterion, the lymph node clinical target volume was defined as the area encompassed by a 7 mm margin around the applicable pelvic vessels. Modifications were made in each nodal area to cover adjacent adipose tissues at risk of microscopic nodal metastases. Although the bones and muscles were excluded, the bowel was not routinely excluded in the definition. Each of the following pelvic node regions was defined: common iliac, external iliac, internal iliac, obturator and presacral. Anatomical structures bordering each lymph node region were defined for six directions; anterior, posterior, lateral, medial, cranial and caudal. Drafts of the definition and the atlas were reviewed by members of the JCOG Gynecologic Cancer Study Group (GCSG). We developed a consensus-based guideline defining the pelvic node clinical target volumes that included an atlas. The guideline will be continuously updated to reflect the ongoing changes in the field. (author)

Consensus Guidelines for Delineation of Clinical Target Volume for Intensity-Modulated Pelvic Radiotherapy for the Definitive Treatment of Cervix Cancer

International Nuclear Information System (INIS)

Lim, Karen; Small, William; Portelance, Lorraine; Creutzberg, Carien; Juergenliemk-Schulz, Ina M.; Mundt, Arno; Mell, Loren K.; Mayr, Nina; Viswanathan, Akila; Jhingran, Anuja; Erickson, Beth; De Los Santos, Jennifer; Gaffney, David; Yashar, Catheryn; Beriwal, Sushil; Wolfson, Aaron

2011-01-01

Purpose: Accurate target definition is vitally important for definitive treatment of cervix cancer with intensity-modulated radiotherapy (IMRT), yet a definition of clinical target volume (CTV) remains variable within the literature. The aim of this study was to develop a consensus CTV definition in preparation for a Phase 2 clinical trial being planned by the Radiation Therapy Oncology Group. Methods and Materials: A guidelines consensus working group meeting was convened in June 2008 for the purposes of developing target definition guidelines for IMRT for the intact cervix. A draft document of recommendations for CTV definition was created and used to aid in contouring a clinical case. The clinical case was then analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with kappa statistics as a measure of agreement between participants. Results: Nineteen experts in gynecological radiation oncology generated contours on axial magnetic resonance images of the pelvis. Substantial STAPLE agreement sensitivity and specificity values were seen for gross tumor volume (GTV) delineation (0.84 and 0.96, respectively) with a kappa statistic of 0.68 (p < 0.0001). Agreement for delineation of cervix, uterus, vagina, and parametria was moderate. Conclusions: This report provides guidelines for CTV definition in the definitive cervix cancer setting for the purposes of IMRT, building on previously published guidelines for IMRT in the postoperative setting.

Reformulation of a clinical-dose system for carbon-ion radiotherapy treatment planning at the National Institute of Radiological Sciences, Japan

International Nuclear Information System (INIS)

Inaniwa, Taku; Kanematsu, Nobuyuki; Matsufuji, Naruhiro; Shirai, Toshiyuki; Noda, Koji; Kanai, Tatsuaki; Tsuji, Hiroshi; Kamada, Tadashi; Tsujii, Hirohiko

2015-01-01

At the National Institute of Radiological Sciences (NIRS), more than 8,000 patients have been treated for various tumors with carbon-ion (C-ion) radiotherapy in the past 20 years based on a radiobiologically defined clinical-dose system. Through clinical experience, including extensive dose escalation studies, optimum dose-fractionation protocols have been established for respective tumors, which may be considered as the standards in C-ion radiotherapy. Although the therapeutic appropriateness of the clinical-dose system has been widely demonstrated by clinical results, the system incorporates several oversimplifications such as dose-independent relative biological effectiveness (RBE), empirical nuclear fragmentation model, and use of dose-averaged linear energy transfer to represent the spectrum of particles. We took the opportunity to update the clinical-dose system at the time we started clinical treatment with pencil beam scanning, a new beam delivery method, in 2011. The requirements for the updated system were to correct the oversimplifications made in the original system, while harmonizing with the original system to maintain the established dose-fractionation protocols. In the updated system, the radiation quality of the therapeutic C-ion beam was derived with Monte Carlo simulations, and its biological effectiveness was predicted with a theoretical model. We selected the most used C-ion beam with α r = 0.764 Gy −1 and β = 0.0615 Gy −2 as reference radiation for RBE. The C-equivalent biological dose distribution is designed to allow the prescribed survival of tumor cells of the human salivary gland (HSG) in entire spread-out Bragg peak (SOBP) region, with consideration to the dose dependence of the RBE. This C-equivalent biological dose distribution is scaled to a clinical dose distribution to harmonize with our clinical experiences with C-ion radiotherapy. Treatment plans were made with the original and the updated clinical-dose systems, and both

Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets- An Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development

Science.gov (United States)

Ilekis, John V.; Tsilou, Ekaterini; Fisher, Susan; Abrahams, Vikki M.; Soares, Michael J.; Cross, James C.; Zamudio, Stacy; Illsley, Nicholas P.; Myatt, Leslie; Colvis, Christine; Costantine, Maged M.; Haas, David M.; Sadovsky, Yoel; Weiner, Carl; Rytting, Erik; Bidwell, Gene

2016-01-01

Although much progress is being made in understanding the molecular pathways in the placenta involved in the pathophysiology of pregnancy related disorders, a significant gap exists in utilizing this information for developing new drug therapies to improve pregnancy outcome. On March 5–6, 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health sponsored a two day workshop titled Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets to begin to address this gap. Particular emphasis was given in the identification of important molecular pathways that could serve as drug targets and the advantages and disadvantages of targeting these particular pathways. This article is a summary of the proceedings of this workshop. A broad number of topics were covered ranging from basic placental biology to clinical trials. This included research in the basic biology of placentation, such as trophoblast migration and spiral artery remodeling, and trophoblast sensing and response to infectious and non-infectious agents. Research findings in these areas will be critical for formulating developing future treatments and developing therapies for the prevention of a number of pregnancy disorders of placental origin including preeclampsia, fetal growth restriction, and uterine inflammation. Research was also presented summarizing ongoing clinical efforts in the U.S. and in Europe testing novel interventions for preeclampsia and fetal growth restriction, including agents such as oral arginine supplementation, sildenafil, pravastatin, gene therapy using virally-delivered vascular endothelial growth factor, and oxygen supplementation therapy. Strategies were also proposed to improve fetal growth by enhancing nutrient transport to the fetus by modulating their placental transporters, as well as targeting placental mitochondrial dysfunction and oxidative stress to improve placental health. The roles

Use of national clinical databases for informing and for evaluating health care policies.

Science.gov (United States)

Black, Nick; Tan, Stefanie

2013-02-01

Policy-makers and analysts could make use of national clinical databases either to inform or to evaluate meso-level (organisation and delivery of health care) and macro-level (national) policies. Reviewing the use of 15 of the best established databases in England, we identify and describe four published examples of each use. These show that policy-makers can either make use of the data itself or of research based on the database. For evaluating policies, the major advantages are the huge sample sizes available, the generalisability of the data, its immediate availability and historic information. The principal methodological challenges involve the need for risk adjustment and time-series analysis. Given their usefulness in the policy arena, there are several reasons why national clinical databases have not been used more, some due to a lack of 'push' by their custodians and some to the lack of 'pull' by policy-makers. Greater exploitation of these valuable resources would be facilitated by policy-makers' and custodians' increased awareness, minimisation of legal restrictions on data use, improvements in the quality of databases and a library of examples of applications to policy. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Energy performance certificates and 3-dimensional city models as a means to reach national targets – A case study of the city of Kiruna

International Nuclear Information System (INIS)

Johansson, Tim; Vesterlund, Mattias; Olofsson, Thomas; Dahl, Jan

2016-01-01

Highlights: • Visualization of energy use is a useful tool for energy advisors. • Feature Manipulation Engine can be used for visualization of data from energy certificates. • Multi data visualization from the energy certificates can be preformed. • Future scenarios can be calculated and analyzed. • The case study shows that the national levels for energy reduction will be hard to fulfill. - Abstract: Enhanced dissemination of information regarding energy saving and climate change targeted toward property owners is considered to be an important strategy in order to reach the Swedish national target of energy efficiency in the building sector by 2050. Here the municipality energy advisors and the national register for energy performance certificates can facilitate the mitigation of energy use in the building stock. So far few studies have focused on the practical road map to the national target of energy use on the city/district level and to the communication aspects with stakeholders in the creation of energy city models. In this paper a city energy model is developed based on the requests and need for visualization from a group of energy advisors. Six different scenarios are studied in order to analyze the possibility of reaching the energy targets specified by the government in the town of Kiruna. The results show that: (1) it is possible to automatically create city energy models using extract, transform and load tools based on spatial and non-spatial data from national registers and databases; (2) city energy models improve the understanding of energy use in buildings and can therefore be a valuable tool for energy advisors, real estate companies and urban planners. The case study of Kiruna showed that the proposed energy saving measures in the energy performance certificates need to be implemented and new buildings in the urban transformation must be of high energy standard in order to reach the national target in Kiruna.

Targeted hepatic sonography during clinic visits for detection of fatty liver in overweight children: a pilot study.

Science.gov (United States)

Perito, Emily R; Tsai, Patrika M; Hawley, Sarah; Lustig, Robert H; Feldstein, Vickie A

2013-04-01

The purpose of this study was to assess the feasibility and utility of targeted hepatic sonography to evaluate for hepatic steatosis during a subspecialty clinic visit. In this pilot study, we performed targeted hepatic sonography on 25 overweight children aged 7 to 17 years consecutively seen in a pediatric obesity clinic. Long-axis images of the right lobe of the liver and a split-screen image of liver and spleen were taken. Images were interpreted in real time by the radiologist and shown to the family. Demographics, clinical measurements, and laboratory parameters were also collected from the specialty clinic visit on the same day. Sonography required a median of 4 minutes during the visit (interquartile range, 3-5 minutes). All consented patients completed the study. The median alanine aminotransferase (ALT) level was 23 U/L in those with no steatosis (n = 14), 26 U/L with mild steatosis (n = 6), and 41 U/L with moderate/marked steatosis (n = 5). Children with ALT levels of 25 to 50 U/L had very variable sonographic measures of hepatic steatosis. When the participants were categorized by the overall degree of fatty liver, hepatic steatosis was significantly associated with the aspartate aminotransferase level (P = .028), ALT level (P = .003), and diastolic blood pressure (P = .05) but did not correlate with age, sex, Latino race, or insulin resistance. Targeted hepatic sonography added information not apparent from routine ALT screening and provided immediate feedback to clinicians and families about the effect of obesity on end organs. This examination could be a feasible, informative addition to screening for children at high risk for nonalcoholic fatty liver disease who are seen in clinics that specialize in obesity.

Characterization of third-harmonic target plan irradiance on the National Ignition Facility Beamlet demonstration project

International Nuclear Information System (INIS)

Wegner, P.J.; Van Wonterghem, B.M.; Dixit, S.N.; Henesian, M.A.; Barker, C.E.; Thompson, C.E.; Seppala, L.G.; Caird, J.A.

1997-01-01

The Beamlet laser is a single-aperture prototype for the National Ignition Facility (NIF). We have recently installed and activated a 55 m 3 vacuum vessel and associated diagnostic package at the output of the Beamlet that we are using to characterize target plane irradiance at high power. Measurements obtained both with and without a kinoform diffractive optic are reported. Dependences on critical laser parameters including output power, spatial filtering, and wavefront correction are discussed and compared with simulations

Utilize target motion to cover clinical target volume (ctv) - a novel and practical treatment planning approach to manage respiratory motion

International Nuclear Information System (INIS)

Jin Jianyue; Ajlouni, Munther; Kong Fengming; Ryu, Samuel; Chetty, Indrin J.; Movsas, Benjamin

2008-01-01

Purpose: To use probability density function (PDF) to model motion effects and incorporate this information into treatment planning for lung cancers. Material and methods: PDFs were calculated from the respiratory motion traces of 10 patients. Motion effects were evaluated by convolving static dose distributions with various PDFs. Based on a differential dose prescription with relatively lower dose to the clinical target volume (CTV) than to the gross tumor volume (GTV), two approaches were proposed to incorporate PDFs into treatment planning. The first approach uses the GTV-based internal target volume (ITV) as the planning target volume (PTV) to ensure full dose to the GTV, and utilizes the motion-induced dose gradient to cover the CTV. The second approach employs an inhomogeneous static dose distribution within a minimized PTV to best match the prescription dose gradient. Results: Motion effects on dose distributions were minimal in the anterior-posterior (AP) and lateral directions: a 10-mm motion only induced about 3% of dose reduction in the peripheral target region. The motion effect was remarkable in the cranial-caudal direction. It varied with the motion amplitude, but tended to be similar for various respiratory patterns. For the first approach, a 10-15 mm motion would adequately cover the CTV (presumed to be 60-70% of the GTV dose) without employing the CTV in planning. For motions 15-mm. An example of inhomogeneous static dose distribution in a reduced PTV was given, and it showed significant dose reduction in the normal tissue without compromising target coverage. Conclusions: Respiratory motion-induced dose gradient can be utilized to cover the CTV and minimize the lung dose without the need for more sophisticated technologies

Optimized beryllium target design for indirectly driven inertial confinement fusion experiments on the National Ignition Facility

Energy Technology Data Exchange (ETDEWEB)

Simakov, Andrei N., E-mail: simakov@lanl.gov; Wilson, Douglas C.; Yi, Sunghwan A.; Kline, John L.; Batha, Steven H. [Los Alamos National Laboratory, P.O. Box 1663, Los Alamos, New Mexico 87545 (United States); Clark, Daniel S.; Milovich, Jose L.; Salmonson, Jay D. [Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, California 94551 (United States)

2014-02-15

For indirect drive inertial confinement fusion, Beryllium (Be) ablators offer a number of important advantages as compared with other ablator materials, e.g., plastic and high density carbon. In particular, the low opacity and relatively high density of Be lead to higher rocket efficiencies giving a higher fuel implosion velocity for a given X-ray drive; and to higher ablation velocities providing more ablative stabilization and reducing the effect of hydrodynamic instabilities on the implosion performance. Be ablator advantages provide a larger target design optimization space and can significantly improve the National Ignition Facility (NIF) [J. D. Lindl et al., Phys. Plasmas 11, 339 (2004)] ignition margin. Herein, we summarize the Be advantages, briefly review NIF Be target history, and present a modern, optimized, low adiabat, Revision 6 NIF Be target design. This design takes advantage of knowledge gained from recent NIF experiments, including more realistic levels of laser-plasma energy backscatter, degraded hohlraum-capsule coupling, and the presence of cross-beam energy transfer.

Conceptual design of low activation target chamber and components for the National Ignition Facility

International Nuclear Information System (INIS)

Streckert, H.H.; Schultz, K.R.; Sager, G.T.; Kantner, R.D.

1996-01-01

The baseline design for the target chamber and chamber components for the National Ignition Facility (NIF) consists of aluminum alloy structural material. Low activation composite chamber and components have important advantages including enhanced environmental and safety characteristics and improved accessibility due to reduced neutron-induced radioactivity. A low activation chamber can be fabricated from carbon fiber reinforced epoxy using thick wall laminate technology similar to submarine bow dome fabrication for the U.S. Navy. A risk assessment analysis indicates that a composite chamber has a reasonably high probability of success, but that an aluminum alloy chamber represents a lower risk. Use of low activation composite materials for several chamber components such as the final optics assemblies, the target positioner and inserter, the diagnostics manipulator tubes, and the optics beam tubes would offer an opportunity to make significant reductions in post-shot radiation dose rate with smaller, less immediate impact on the NIF design. 7 refs., 3 figs

Possible version of the compression degradation of the thermonuclear indirect-irradiation targets at the national ignition facility and a reason for the failure of ignition

Energy Technology Data Exchange (ETDEWEB)

Rozanov, V. B., E-mail: rozanov@sci.lebedev.ru; Vergunova, G. A., E-mail: verg@sci.lebedev.ru [Russian Academy of Sciences, Lebedev Physical Institute (Russian Federation)

2017-01-15

The main parameters of compression of a target and tendencies at change in the irradiation conditions are determined by analyzing the published results of experiments at the megajoule National Ignition Facility (NIF) on the compression of capsules in indirect-irradiation targets by means of the one-dimensional RADIAN program in the spherical geometry. A possible version of the “failure of ignition” of an indirect-irradiation target under the NIF conditions is attributed to radiation transfer. The application of onedimensional model to analyze the National Ignition Campaign (NIC) experiments allows identifying conditions corresponding to the future ignition regime and distinguishing them from conditions under which ignition does not occur.

Clinical applicability and cost of a 46-gene panel for genomic analysis of solid tumours: Retrospective validation and prospective audit in the UK National Health Service.

Directory of Open Access Journals (Sweden)

Angela Hamblin

2017-02-01

Full Text Available Single gene tests to predict whether cancers respond to specific targeted therapies are performed increasingly often. Advances in sequencing technology, collectively referred to as next generation sequencing (NGS, mean the entire cancer genome or parts of it can now be sequenced at speed with increased depth and sensitivity. However, translation of NGS into routine cancer care has been slow. Healthcare stakeholders are unclear about the clinical utility of NGS and are concerned it could be an expensive addition to cancer diagnostics, rather than an affordable alternative to single gene testing.We validated a 46-gene hotspot cancer panel assay allowing multiple gene testing from small diagnostic biopsies. From 1 January 2013 to 31 December 2013, solid tumour samples (including non-small-cell lung carcinoma [NSCLC], colorectal carcinoma, and melanoma were sequenced in the context of the UK National Health Service from 351 consecutively submitted prospective cases for which treating clinicians thought the patient had potential to benefit from more extensive genetic analysis. Following histological assessment, tumour-rich regions of formalin-fixed paraffin-embedded (FFPE sections underwent macrodissection, DNA extraction, NGS, and analysis using a pipeline centred on Torrent Suite software. With a median turnaround time of seven working days, an integrated clinical report was produced indicating the variants detected, including those with potential diagnostic, prognostic, therapeutic, or clinical trial entry implications. Accompanying phenotypic data were collected, and a detailed cost analysis of the panel compared with single gene testing was undertaken to assess affordability for routine patient care. Panel sequencing was successful for 97% (342/351 of tumour samples in the prospective cohort and showed 100% concordance with known mutations (detected using cobas assays. At least one mutation was identified in 87% (296/342 of tumours. A locally

Reaching national consensus on the core clinical skill outcomes for family medicine postgraduate training programmes in South Africa.

Science.gov (United States)

Akoojee, Yusuf; Mash, Robert

2017-05-26

Family physicians play a significant role in the district health system and need to be equipped with a broad range of clinical skills in order to meet the needs and expectations of the communities they serve. A previous study in 2007 reached national consensus on the clinical skills that should be taught in postgraduate family medicine training prior to the introduction of the new speciality. Since then, family physicians have been trained, employed and have gained experience of working in the district health services. The national Education and Training Committee of the South African Academy of Family Physicians, therefore, requested a review of the national consensus on clinical skills for family medicine training. A Delphi technique was used to reach national consensus in a panel of 17 experts: family physicians responsible for training, experienced family physicians in practice and managers responsible for employing family physicians. Consensus was reached on 242 skills from which the panel decided on 211 core skills, 28 elective skills and 3 skills to be deleted from the previous list. The panel was unable to reach consensus on 11 skills. The findings will guide training programmes on the skills to be addressed and ensure consistency across training programmes nationally. The consensus will also guide formative assessment as documented in the national portfolio of learning and summative assessment in the national exit examination. The consensus will be of interest to other countries in the region where training programmes in family medicine are developing.

National turnaround time survey: professional consensus standards for optimal performance and thresholds considered to compromise efficient and effective clinical management.

Science.gov (United States)

McKillop, Derek J; Auld, Peter

2017-01-01

Background Turnaround time can be defined as the time from receipt of a sample by the laboratory to the validation of the result. The Royal College of Pathologists recommends that a number of performance indicators for turnaround time should be agreed with stakeholders. The difficulty is in arriving at a goal which has some evidence base to support it other than what may simply be currently achievable technically. This survey sought to establish a professional consensus on the goals and meaning of targets for laboratory turnaround time. Methods A questionnaire was circulated by the National Audit Committee to 173 lead consultants for biochemistry in the UK. The survey asked each participant to state their current target turnaround time for core investigations in a broad group of clinical settings. Each participant was also asked to provide a professional opinion on what turnaround time would pose an unacceptable risk to patient safety for each departmental category. A super majority (2/3) was selected as the threshold for consensus. Results The overall response rate was 58% ( n = 100) with a range of 49-72% across the individual Association for Clinical Biochemistry and Laboratory Medicine regions. The consensus optimal turnaround time for the emergency department was 2 h considered unacceptable. The times for general practice and outpatient department were 48 h and for Wards 12 h, respectively. Conclusions We consider that the figures provide a useful benchmark of current opinion, but clearly more empirical standards will have to develop alongside other aspects of healthcare delivery.

Indirect-drive noncryogenic double-shell ignition targets for the National Ignition Facility: Design and analysis

International Nuclear Information System (INIS)

Amendt, Peter; Colvin, J.D.; Tipton, R.E.; Hinkel, D.E.; Edwards, M.J.; Landen, O.L.; Ramshaw, J.D.; Suter, L.J.; Varnum, W.S.; Watt, R.G.

2002-01-01

Analysis and design of indirect-drive National Ignition Facility double-shell targets with hohlraum temperatures of 200 eV and 250 eV are presented. The analysis of these targets includes the assessment of two-dimensional radiation asymmetry and nonlinear mix. Two-dimensional integrated hohlraum simulations indicate that the x-ray illumination can be adjusted to provide adequate symmetry control in hohlraums specially designed to have high laser-coupling efficiency [Suter et al., Phys. Plasmas 7, 2092 (2000)]. These simulations also reveal the need to diagnose and control localized 10-15 keV x-ray emission from the high-Z hohlraum wall because of strong absorption by the high-Z inner shell. Preliminary estimates of the degree of laser backscatter from an assortment of laser-plasma interactions suggest comparatively benign hohlraum conditions. The application of a variety of nonlinear mix models and phenomenological tools, including buoyancy-drag models, multimode simulations and fall-line optimization, indicates a possibility of achieving ignition, i.e., fusion yields greater than 1 MJ. Planned experiments on the Omega laser will test current understanding of high-energy radiation flux asymmetry and mix-induced yield degradation in double-shell targets

Seasonal Influenza Vaccine Uptake in a Respiratory Outpatients Clinic

LENUS (Irish Health Repository)

Rossiter, A

2017-02-01

Influenza is an acute viral respiratory illness that continues to cause significant morbidity and mortality in Ireland. Despite well-established national and international guidelines1 and increased public awareness campaigns, vaccine uptake rates are well below target worldwide2. We performed an audit of influenza vaccine uptake at a Respiratory outpatient clinic in a tertiary referral centre. 54% (n=41) of patients received the annual vaccine, well below the target of 75% set by the European Centre for Disease Prevention and Control (ECDC).

Visually directed vs. software-based targeted biopsy compared to transperineal template mapping biopsy in the detection of clinically significant prostate cancer.

Science.gov (United States)

Valerio, Massimo; McCartan, Neil; Freeman, Alex; Punwani, Shonit; Emberton, Mark; Ahmed, Hashim U

2015-10-01

Targeted biopsy based on cognitive or software magnetic resonance imaging (MRI) to transrectal ultrasound registration seems to increase the detection rate of clinically significant prostate cancer as compared with standard biopsy. However, these strategies have not been directly compared against an accurate test yet. The aim of this study was to obtain pilot data on the diagnostic ability of visually directed targeted biopsy vs. software-based targeted biopsy, considering transperineal template mapping (TPM) biopsy as the reference test. Prospective paired cohort study included 50 consecutive men undergoing TPM with one or more visible targets detected on preoperative multiparametric MRI. Targets were contoured on the Biojet software. Patients initially underwent software-based targeted biopsies, then visually directed targeted biopsies, and finally systematic TPM. The detection rate of clinically significant disease (Gleason score ≥3+4 and/or maximum cancer core length ≥4mm) of one strategy against another was compared by 3×3 contingency tables. Secondary analyses were performed using a less stringent threshold of significance (Gleason score ≥4+3 and/or maximum cancer core length ≥6mm). Median age was 68 (interquartile range: 63-73); median prostate-specific antigen level was 7.9ng/mL (6.4-10.2). A total of 79 targets were detected with a mean of 1.6 targets per patient. Of these, 27 (34%), 28 (35%), and 24 (31%) were scored 3, 4, and 5, respectively. At a patient level, the detection rate was 32 (64%), 34 (68%), and 38 (76%) for visually directed targeted, software-based biopsy, and TPM, respectively. Combining the 2 targeted strategies would have led to detection rate of 39 (78%). At a patient level and at a target level, software-based targeted biopsy found more clinically significant diseases than did visually directed targeted biopsy, although this was not statistically significant (22% vs. 14%, P = 0.48; 51.9% vs. 44.3%, P = 0.24). Secondary

Z-pinch driven inertial confinement fusion target physics research at Sandia National Laboratories

International Nuclear Information System (INIS)

Leeper, R.J.; Alberts, T.E.; Asay, J.R.

2001-01-01

Three hohlraum concepts are being pursued at Sandia National Laboratories (SNL) to investigate the possibility of using pulsed power driven magnetic implosions (z-pinches) to drive high gain targets capable of yields in the range of 200-1000 MJ. This research is being conducted on SNL's Z facility that is capable of driving peak currents of 20 MA in z-pinch loads producing implosion velocities as high as 7.5x10 7 cm/s, x-ray energies approaching 2 MJ, and x-ray powers exceeding 200 TW. This paper will discuss each of these hohlraum concepts and will overview the experiments that have been conducted on these systems to date. (author)

The National Hip Fracture Database (NHFD) - Using a national clinical audit to raise standards of nursing care.

Science.gov (United States)

Johansen, Antony; Boulton, Christopher; Hertz, Karen; Ellis, Michael; Burgon, Vivienne; Rai, Sunil; Wakeman, Rob

2017-08-01

The National Hip Fracture Database (NHFD) is a key clinical governance programme for staff working in trauma wards across England, Wales and Northern Ireland. It uses prospectively collected information about the 65,000 people who present with hip fracture each year, and links these with information about the quality of care and outcome for each individual. The NHFD can, therefore, provide a picture of the care offered to frail older people with this injury - people who, between them, occupy nearly half of inpatient trauma beds. The NHFD uses its website (www.nhfd.co.uk) to feed back live information to each of the countries' 180 trauma units - allowing them to bench mark their performance against national standards, and against that in other hospitals. This helps to develop a consensus over the best care for frail older people in areas where national guidance is not yet available. This article shows how the NHFD is contributing to four key aspects of patient safety and nursing care: the prevention of pressure ulcers and post-operative delirium, the monitoring of falls incidence across hospitals and nutritional assessment of patients with hip fracture. Copyright © 2017 Elsevier Ltd. All rights reserved.

National Mesothelioma Virtual Bank: A standard based biospecimen and clinical data resource to enhance translational research

Directory of Open Access Journals (Sweden)

Valdivieso Federico A

2008-08-01

Full Text Available Abstract Background Advances in translational research have led to the need for well characterized biospecimens for research. The National Mesothelioma Virtual Bank is an initiative which collects annotated datasets relevant to human mesothelioma to develop an enterprising biospecimen resource to fulfill researchers' need. Methods The National Mesothelioma Virtual Bank architecture is based on three major components: (a common data elements (based on College of American Pathologists protocol and National North American Association of Central Cancer Registries standards, (b clinical and epidemiologic data annotation, and (c data query tools. These tools work interoperably to standardize the entire process of annotation. The National Mesothelioma Virtual Bank tool is based upon the caTISSUE Clinical Annotation Engine, developed by the University of Pittsburgh in cooperation with the Cancer Biomedical Informatics Grid™ (caBIG™, see http://cabig.nci.nih.gov. This application provides a web-based system for annotating, importing and searching mesothelioma cases. The underlying information model is constructed utilizing Unified Modeling Language class diagrams, hierarchical relationships and Enterprise Architect software. Result The database provides researchers real-time access to richly annotated specimens and integral information related to mesothelioma. The data disclosed is tightly regulated depending upon users' authorization and depending on the participating institute that is amenable to the local Institutional Review Board and regulation committee reviews. Conclusion The National Mesothelioma Virtual Bank currently has over 600 annotated cases available for researchers that include paraffin embedded tissues, tissue microarrays, serum and genomic DNA. The National Mesothelioma Virtual Bank is a virtual biospecimen registry with robust translational biomedical informatics support to facilitate basic science, clinical, and translational

Key principles for a national clinical decision support knowledge sharing framework: synthesis of insights from leading subject matter experts.

Science.gov (United States)

Kawamoto, Kensaku; Hongsermeier, Tonya; Wright, Adam; Lewis, Janet; Bell, Douglas S; Middleton, Blackford

2013-01-01

To identify key principles for establishing a national clinical decision support (CDS) knowledge sharing framework. As part of an initiative by the US Office of the National Coordinator for Health IT (ONC) to establish a framework for national CDS knowledge sharing, key stakeholders were identified. Stakeholders' viewpoints were obtained through surveys and in-depth interviews, and findings and relevant insights were summarized. Based on these insights, key principles were formulated for establishing a national CDS knowledge sharing framework. Nineteen key stakeholders were recruited, including six executives from electronic health record system vendors, seven executives from knowledge content producers, three executives from healthcare provider organizations, and three additional experts in clinical informatics. Based on these stakeholders' insights, five key principles were identified for effectively sharing CDS knowledge nationally. These principles are (1) prioritize and support the creation and maintenance of a national CDS knowledge sharing framework; (2) facilitate the development of high-value content and tooling, preferably in an open-source manner; (3) accelerate the development or licensing of required, pragmatic standards; (4) acknowledge and address medicolegal liability concerns; and (5) establish a self-sustaining business model. Based on the principles identified, a roadmap for national CDS knowledge sharing was developed through the ONC's Advancing CDS initiative. The study findings may serve as a useful guide for ongoing activities by the ONC and others to establish a national framework for sharing CDS knowledge and improving clinical care.

The co registration of initial PET on the CT-radiotherapy reduces significantly the variabilities of anatomo-clinical target volume in the child hodgkin disease

International Nuclear Information System (INIS)

Metwally, H.; Blouet, A.; David, I.; Rives, M.; Izar, F.; Courbon, F.; Filleron, T.; Laprie, A.; Plat, G.; Vial, J.

2009-01-01

It exists a great interobserver variability for the anatomo-clinical target volume (C.T.V.) definition in children suffering of Hodgkin disease. In this study, the co-registration of the PET with F.D.G. on the planning computed tomography has significantly lead to a greater coherence in the clinical target volume definition. (N.C.)

CGRP as the target of new migraine therapies - successful translation from bench to clinic.

Science.gov (United States)

Edvinsson, Lars; Haanes, Kristian Agmund; Warfvinge, Karin; Krause, Diana N

2018-06-01

Treatment of migraine is on the cusp of a new era with the development of drugs that target the trigeminal sensory neuropeptide calcitonin gene-related peptide (CGRP) or its receptor. Several of these drugs are expected to receive approval for use in migraine headache in 2018 and 2019. CGRP-related therapies offer considerable improvements over existing drugs as they are the first to be designed specifically to act on the trigeminal pain system, they are more specific and they seem to have few or no adverse effects. CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks. As these drugs come into clinical use, we provide an overview of knowledge that has led to successful development of these drugs. We describe the biology of CGRP signalling, summarize key clinical evidence for the role of CGRP in migraine headache, including the efficacy of CGRP-targeted treatment, and synthesize what is known about the role of CGRP in the trigeminovascular system. Finally, we consider how the latest findings provide new insight into the central role of the trigeminal ganglion in the pathophysiology of migraine.

Patient-specific prescriber feedback can increase the rate of osteoporosis screening and treatment: results from two national interventions.

Science.gov (United States)

Kalisch Ellett, Lisa M; Pratt, N L; Sluggett, J K; Ramsay, E N; Kerr, M; LeBlanc, V T; Barratt, J D; Roughead, E E

2017-12-01

Osteoporosis interventions targeting older Australians and clinicians were conducted in 2008 and 2011 as part of a national quality improvement program underpinned by behavioural theory and stakeholder engagement. Uptake of bone mineral density (BMD) tests among targeted men and women increased after both interventions and sustained increases in osteoporosis treatment were observed among men targeted in 2008. Educational interventions incorporating patient-specific prescriber feedback have improved osteoporosis screening and treatment among at-risk patients in clinical trials but have not been evaluated nationally. This study assessed uptake of BMD testing and osteoporosis medicines following two national Australian quality improvement initiatives targeting women (70-79 years) and men (75-85 years) at risk of osteoporosis. Administrative health claims data were used to determine monthly rates of BMD testing and initiation of osteoporosis medicines in the 9-months post-intervention among targeted men and women compared to older cohorts of men and women. Log binomial regression models were used to assess differences between groups. In 2008 91,794 patients were targeted and 52,427 were targeted in 2011. There was a twofold increase in BMD testing after each intervention among targeted patients compared to controls (p theory and stakeholder engagement that target both primary care clinicians and patients can improve osteoporosis screening and management at the national level.

The FORGE AHEAD clinical readiness consultation tool: a validated tool to assess clinical readiness for chronic disease care mobilization in Canada's First Nations.

Science.gov (United States)

Hayward, Mariam Naqshbandi; Mequanint, Selam; Paquette-Warren, Jann; Bailie, Ross; Chirila, Alexandra; Dyck, Roland; Green, Michael; Hanley, Anthony; Tompkins, Jordan; Harris, Stewart

2017-03-23

Given the astounding rates of diabetes and related complications, and the barriers to providing care present in Indigenous communities in Canada, intervention strategies that take into account contextual factors such as readiness to mobilize are needed to maximize improvements and increase the likelihood of success and sustainment. As part of the national FORGE AHEAD Program, we sought to develop, test and validate a clinical readiness consultation tool aimed at assessing the readiness of clinical teams working on-reserve in First Nations communities to participate in quality improvement (QI) to enhance diabetes care in Canada. A literature review was conducted to identify existing readiness tools. The ABCD - SAT was adapted using a consensus approach that emphasized a community-based participatory approach and prioritized the knowledge and wisdom held by community members. The tool was piloted with a group of 16 people from 7 provinces and 11 partnering communities to assess language use, clarity, relevance, format, and ease of completion using examples. Internal reliability analysis and convergence validity were conducted with data from 53 clinical team members from 11 First Nations communities (3-5 per community) who have participated in the FORGE AHEAD program. The 27-page Clinical Readiness Consultation Tool (CRCT) consists of five main components, 21 sub-components, and 74 items that are aligned with the Expanded Chronic Care Model. Five-point Likert scale feedback from the pilot ranged from 3.25 to 4.5. Length of the tool was reported as a drawback but respondents noted that all the items were needed to provide a comprehensive picture of the healthcare system. Results for internal consistency showed that all sub-components except for two were within acceptable ranges (0.77-0.93). The Team Structure and Function sub-component scale had a moderately significant positive correlation with the validated Team Climate Inventory, r = 0.45, p < 0.05. The

EGFR targeted nanobody-photosensitizer conjugates for photodynamic therapy in a pre-clinical model of head and neck cancer.

Science.gov (United States)

van Driel, Pieter B A A; Boonstra, Martin C; Slooter, Maxime D; Heukers, Raimond; Stammes, Marieke A; Snoeks, Thomas J A; de Bruijn, Henriette S; van Diest, Paul J; Vahrmeijer, Alexander L; van Bergen En Henegouwen, Paul M P; van de Velde, Cornelis J H; Löwik, Clemens W G M; Robinson, Dominic J; Oliveira, Sabrina

2016-05-10

Photodynamic therapy (PDT) induces cell death through local light activation of a photosensitizer (PS) and has been used to treat head and neck cancers. Yet, common PS lack tumor specificity, which leads to collateral damage to normal tissues. Targeted delivery of PS via antibodies has pre-clinically improved tumor selectivity. However, antibodies have long half-lives and relatively poor tissue penetration, which could limit therapeutic efficacy and lead to long photosensitivity. Here, in this feasibility study, we evaluate at the pre-clinical level a recently introduced format of targeted PDT, which employs nanobodies as targeting agents and a water-soluble PS (IRDye700DX) that is traceable through optical imaging. In vitro, the PS solely binds to cells and induces phototoxicity on cells overexpressing the epidermal growth factor receptor (EGFR), when conjugated to the EGFR targeted nanobodies. To investigate whether this new format of targeted PDT is capable of inducing selective tumor cell death in vivo, PDT was applied on an orthotopic mouse tumor model with illumination at 1h post-injection of the nanobody-PS conjugates, as selected from quantitative fluorescence spectroscopy measurements. In parallel, and as a reference, PDT was applied with an antibody-PS conjugate, with illumination performed 24h post-injection. Importantly, EGFR targeted nanobody-PS conjugates led to extensive tumor necrosis (approx. 90%) and almost no toxicity in healthy tissues, as observed through histology 24h after PDT. Overall, results show that these EGFR targeted nanobody-PS conjugates are selective and able to induce tumor cell death in vivo. Additional studies are now needed to assess the full potential of this approach to improving PDT. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Overview of Self-Management Resources Used by Canadian Chronic Kidney Disease Clinics: A National Survey.

Science.gov (United States)

Donald, Maoliosa; Gil, Sarah; Kahlon, Bhavneet; Beanlands, Heather; Straus, Sharon; Herrington, Gwen; Manns, Braden; Hemmelgarn, Brenda R

2018-01-01

Chronic kidney disease (CKD) clinics across Canada provide tailored care for patients with CKD with an aim to slow progression and prevent complications. These clinics provide CKD self-management resources; however, there is limited information about what resources are being used by clinics. We undertook a survey of CKD clinics across Canada to identify self-management resources for adults aged 18 years and over with CKD categories 1 to 5 and not requiring dialysis or transplant. To identify and collate self-management resources (eg, strategies, tools, educational materials) used by CKD clinics across Canada for adults with CKD (categories 1 to 5, not requiring kidney replacement therapy). Self-administered, semistructured electronic survey. Canadian CKD clinics with previously identified contact information. We contacted 57 CKD English-speaking clinics and invited them to complete an online survey. The survey was available from October 2016 to January 2017 and consisted of 17 questions regarding the use and attributes of self-management resources including topic, delivery format, provider, target population, where the intervention was provided, and resource languages. Forty-four clinics (77%) completed the survey. The most common topic was modality education provided in print format, by nurses. The most frequently used resource was the Kidney Foundation of Canada (KFOC) Living With Kidney Disease manual. We also identified that the majority of resources were available in English, targeting both patients and caregivers in the outpatient setting. Our survey included Canadian adult CKD clinics, which may not be generalizability to other settings, such as care of people with CKD in primary care. Adult CKD clinics across Canada provide some similar resources, but also provide many different self-management resources. Even though some of the same resources were used by multiple clinics, the way they were provided them (ie, provider, location, delivery format) varied by

An evaluation on the impact of national cancer wait targets on a (UK) radiotherapy department

International Nuclear Information System (INIS)

Roberts, Neill

2012-01-01

The radiotherapy department in this evaluation has been working towards full compliance with national cancer wait targets (CWT) since their implementation. 31 and 62 day targets set a maximum time frame for cancer patients to commence treatment. This evaluation explored the impact of these targets on staff and patients within the radiotherapy department and their overall impact on the radiotherapy service. Methods: This evaluation followed a mixed method approach of sequential triangulation. Qualitative data collection and analysis dominate findings but existing quantitative data, available within the department, was used to support the overall findings. Staff and patient interviews were used to establish attitudes to and experiences of the CWT initiative in relation to radiotherapy treatment. Quantitative data was taken from the local Cancer Centre CWT database that tracks patients referred for radiotherapy. Findings and Conclusion: Qualitative data analysis identified four main themes: pressure, appropriateness of target lengths, quality of treatment provided and efficiency of working practices within the department. Responses within these themes were both positive and negative with patients mainly the former and staff the latter. Quantitative evaluation found an increased monitoring and management burden from the CWT initiative, primarily for administrative, clerical and managerial staff. The main impact of the CWT initiative was an increase in pressure on staff due to reduced time to prepare and deliver treatment. Patients felt the initiative had not impacted negatively on their care and experienced a reduction in anxiety due to a reduction in waiting time.

Expanding the National Drug Abuse Treatment Clinical Trials Network to address the management of substance use disorders in general medical settings

Directory of Open Access Journals (Sweden)

Tai B

2014-07-01

Full Text Available Betty Tai, Steven Sparenborg, Udi E Ghitza, David Liu Center for the Clinical Trials Network, National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland, USA Abstract: The Patient Protection and Affordable Care Act (2010 and the Mental Health Parity and Addiction Equity Act (2008 expand substance use disorder (SUD care services in the USA into general medical settings. Care offered in these settings will engage substance-using patients in an integrated and patient-centered environment that addresses physical and mental health comorbidities and follows a chronic care model. This expansion of SUD services presents a great need for evidence-based practices useful in general medical settings, and reveals several research gaps to be addressed. The National Drug Abuse Treatment Clinical Trials Network of the National Institute on Drug Abuse can serve an important role in this endeavor. High-priority research gaps are highlighted in this commentary. A discussion follows on how the National Drug Abuse Treatment Clinical Trials Network can transform to address changing patterns in SUD care to efficiently generate evidence to guide SUD treatment practice within the context of recent US health care legislation. Keywords: Patient Protection and Affordable Care Act, National Drug Abuse Treatment Clinical Trials Network, substance use disorders, practice-based research network, electronic health records

Why providers participate in clinical trials: considering the National Cancer Institute's Community Clinical Oncology Program.

Science.gov (United States)

McAlearney, Ann Scheck; Song, Paula H; Reiter, Kristin L

2012-11-01

The translation of research evidence into practice is facilitated by clinical trials such as those sponsored by the National Cancer Institute's Community Clinical Oncology Program (CCOP) that help disseminate cancer care innovations to community-based physicians and provider organizations. However, CCOP participation involves unsubsidized costs and organizational challenges that raise concerns about sustained provider participation in clinical trials. This study was designed to improve our understanding of why providers participate in the CCOP in order to inform the decision-making process of administrators, clinicians, organizations, and policy-makers considering CCOP participation. We conducted a multi-site qualitative study of five provider organizations engaged with the CCOP. We interviewed 41 administrative and clinician key informants, asking about what motivated CCOP participation, and what benefits they associated with involvement. We deductively and inductively analyzed verbatim interview transcripts, and explored themes that emerged. Interviewees expressed both "altruistic" and "self-interested" motives for CCOP participation. Altruistic reasons included a desire to increase access to clinical trials and feeling an obligation to patients. Self-interested reasons included the desire to enhance reputation, and a need to integrate disparate cancer care activities. Perceived benefits largely matched expressed motives for CCOP participation, and included internal and external benefits to the organization, and quality of care benefits for both patients and participating physicians. The motives and benefits providers attributed to CCOP participation are consistent with translational research goals, offering evidence that participation can contribute value to providers by expanding access to innovative medical care for patients in need. Copyright © 2012 Elsevier Inc. All rights reserved.

Factors Influencing Support for National Health Insurance among Patients Attending Specialist Clinics in Malaysia

Science.gov (United States)

Almualm, Yasmin; Alkaff, Sharifa Ezat; Aljunid, Syed; Alsagoff, Syed Sagoff

2013-01-01

This study was carried out to determine the level of support towards the proposed National Health Insurance scheme among Malaysian patients attending specialist clinics at the National University of Malaysia Medical centre and its influencing factors. The cross sectional study was carried out from July-October 2012. 260 patients were selected using multistage sampling method. 71.2% of respondents supported the proposed National Health insurance scheme. 61.4% of respondents are willing to pay up to RM240 per year to join the National Health Insurance and 76.6% of respondents are of the view that enrolment in NHI should be made compulsory. Knowledge had a positive influence on respondent's support towards National Health Insurance. National Health Insurance when implemented in Malaysia can be used to raise funds for health care financing, increase access to health services and achieve the desired health status. More efforts should be taken to promote the scheme and educate the public in order to achieve higher support towards the proposed National Health Insurance. The cost to enroll in NHI as well as services to be included under the scheme should be duly considered. PMID:23985101

Survey and visual detection of Zaire ebolavirus in clinical samples targeting the nucleoprotein gene in Sierra Leone

Directory of Open Access Journals (Sweden)

Jing Yuan

2015-12-01

Full Text Available Ebola virus (EBOV can lead to severe hemorrhagic fever with a high risk of death in humans and other primates. To guide treatment and prevent spread of the viral infection, a rapid and sensitive detection method is required for clinical samples. Here, we described and evaluated a reverse transcription loop-mediated isothermal amplification (RT-LAMP method to detect Zaire ebolavirus using the nucleoprotein gene (NP as a target sequence. Two different techniques were used, a calcein/Mn2+ complex chromogenic method and real-time turbidity monitoring. The RT-LAMP assay detected the NP target sequence with a limit of 4.56 copies/μL within 45 min under 61°C, a similar even or increase in sensitivity than that of real-time reverse transcription-polymerase chain reaction (RT-PCR. Additionally, all pseudoviral particles or non- Zaire EBOV genomes were negative for LAMP detection, indicating that the assay was highly specific for EBOV. To appraise the availability of the RT-LAMP method for use in clinical diagnosis of EBOV, of 417 blood or swab samples collected from patients with clinically suspected infections in Sierra Leone, 307 were identified for RT-LAMP-based surveillance of EBOV. Therefore, the highly specific and sensitive RT-LAMP method allows the rapid detection of EBOV, and is a suitable tool for clinical screening, diagnosis, and primary quarantine purposes.

Universal Versus Targeted Screening for Lynch Syndrome: Comparing Ascertainment and Costs Based on Clinical Experience.

Science.gov (United States)

Erten, Mujde Z; Fernandez, Luca P; Ng, Hank K; McKinnon, Wendy C; Heald, Brandie; Koliba, Christopher J; Greenblatt, Marc S

2016-10-01

Strategies to screen colorectal cancers (CRCs) for Lynch syndrome are evolving rapidly; the optimal strategy remains uncertain. We compared targeted versus universal screening of CRCs for Lynch syndrome. In 2010-2011, we employed targeted screening (age Lynch syndrome and estimated the 5-year costs of preventing CRC by colonoscopy screening, using a system dynamics model. Using targeted screening, 51/175 (29 %) cancers fit criteria and were tested by immunohistochemistry; 15/51 (29 %, or 8.6 % of all CRCs) showed suspicious loss of ≥1 mismatch repair protein. Germline mismatch repair gene mutations were found in 4/4 cases sequenced (11 suspected cases did not have germline testing). Using universal screening, 17/292 (5.8 %) screened cancers had abnormal immunohistochemistry suspicious for Lynch syndrome. Germline mismatch repair mutations were found in only 3/10 cases sequenced (7 suspected cases did not have germline testing). The mean cost to identify Lynch syndrome probands was ~$23,333/case for targeted screening and ~$175,916/case for universal screening at our institution. Estimated costs to identify and screen probands and relatives were: targeted, $9798/case and universal, $38,452/case. In real-world Lynch syndrome management, incomplete clinical follow-up was the major barrier to do genetic testing. Targeted screening costs 2- to 7.5-fold less than universal and rarely misses Lynch syndrome cases. Future changes in testing costs will likely change the optimal algorithm.

Pearls and pitfalls in clinical interpretation of prostate-specific membrane antigen (PSMA)-targeted PET imaging

Energy Technology Data Exchange (ETDEWEB)

Sheikhbahaei, Sara; Solnes, Lilja B.; Javadi, Mehrbod S.; Pomper, Martin G.; Rowe, Steven P. [Johns Hopkins University School of Medicine, Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Afshar-Oromieh, Ali; Haberkorn, Uwe [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); Eiber, Matthias [David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles, CA (United States); Technical University of Munich, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Ross, Ashley E.; Pienta, Kenneth J.; Allaf, Mohamad E.; Gorin, Michael A. [Johns Hopkins University School of Medicine, The James Buchanan Brady Urological Institute and Department of Urology, Baltimore, MD (United States)

2017-11-15

The rapidly expanding clinical adaptation of prostate-specific membrane antigen (PSMA)-targeted PET imaging in the evaluation of patients with prostate cancer has placed an increasing onus on understanding both the potential pearls of interpretation as well as limitations of this new technique. As with any new molecular imaging modality, accurate characterization of abnormalities on PSMA-targeted PET imaging can be accomplished only if one is aware of the normal distribution pattern, physiological variants of radiotracer uptake, and potential sources of false-positive and false-negative imaging findings. In recent years, a growing number of reports have come to light describing incidental non-prostatic benign or malignant pathologies with high uptake on PSMA-targeted PET imaging. In this review, we have summarized the published literature regarding the potential pearls and technical and interpretive pitfalls of this imaging modality. Knowledge of these limitations can increase the confidence of interpreting physicians and thus improve patient care. As PSMA-targeted PET is expected to be evaluated in larger prospective trials, the dissemination of potential diagnostic pitfalls and the biologic underpinning of those findings will be of increased importance. (orig.)

Pearls and pitfalls in clinical interpretation of prostate-specific membrane antigen (PSMA)-targeted PET imaging

International Nuclear Information System (INIS)

Sheikhbahaei, Sara; Solnes, Lilja B.; Javadi, Mehrbod S.; Pomper, Martin G.; Rowe, Steven P.; Afshar-Oromieh, Ali; Haberkorn, Uwe; Eiber, Matthias; Ross, Ashley E.; Pienta, Kenneth J.; Allaf, Mohamad E.; Gorin, Michael A.

2017-01-01

The rapidly expanding clinical adaptation of prostate-specific membrane antigen (PSMA)-targeted PET imaging in the evaluation of patients with prostate cancer has placed an increasing onus on understanding both the potential pearls of interpretation as well as limitations of this new technique. As with any new molecular imaging modality, accurate characterization of abnormalities on PSMA-targeted PET imaging can be accomplished only if one is aware of the normal distribution pattern, physiological variants of radiotracer uptake, and potential sources of false-positive and false-negative imaging findings. In recent years, a growing number of reports have come to light describing incidental non-prostatic benign or malignant pathologies with high uptake on PSMA-targeted PET imaging. In this review, we have summarized the published literature regarding the potential pearls and technical and interpretive pitfalls of this imaging modality. Knowledge of these limitations can increase the confidence of interpreting physicians and thus improve patient care. As PSMA-targeted PET is expected to be evaluated in larger prospective trials, the dissemination of potential diagnostic pitfalls and the biologic underpinning of those findings will be of increased importance. (orig.)

"Mind the gap!" Evaluation of the performance gap attributable to exception reporting and target thresholds in the new GMS contract: National database analysis

Directory of Open Access Journals (Sweden)

Cookson Richard

2008-06-01

Full Text Available Abstract Background The 2003 revision of the UK GMS contract rewards general practices for performance against clinical quality indicators. Practices can exempt patients from treatment, and can receive maximum payment for less than full coverage of eligible patients. This paper aims to estimate the gap between the percentage of maximum incentive gained and the percentage of patients receiving indicated care (the pay-performance gap, and to estimate how much of the gap is attributable respectively to thresholds and to exception reporting. Methods Analysis of Quality Outcomes Framework data in the National Primary Care Database and exception reporting data from the Information Centre from 8407 practices in England in 2005 – 6. The main outcome measures were the gap between the percentage of maximum incentive gained and the percentage of patients receiving indicated care at the practice level, both for individual indicators and a combined composite score. An additional outcome was the percentage of that gap attributable respectively to exception reporting and maximum threshold targets set at less than 100%. Results The mean pay-performance gap for the 65 aggregated clinical indicators was 13.3% (range 2.9% to 48%. 52% of this gap (6.9% of eligible patients is attributable to thresholds being set at less than 100%, and 48% to patients being exception reported. The gap was greater than 25% in 9 indicators: beta blockers and cholesterol control in heart disease; cholesterol control in stroke; influenza immunization in asthma; blood pressure, sugar and cholesterol control in diabetes; seizures in epilepsy and treatment of hypertension. Conclusion Threshold targets and exception reporting introduce an incentive ceiling, which substantially reduces the percentage of eligible patients that UK practices need to treat in order to receive maximum incentive payments for delivering that care. There are good clinical reasons for exception reporting, but after

Coastal flood implications of 1.5°C, 2°C and 2.5°C global mean temperature stabilization targets for small island nations

Science.gov (United States)

Rasmussen, D.; Buchanan, M. K.; Kopp, R. E.; Oppenheimer, M.

2017-12-01

Sea-level rise (SLR) is magnifying the frequency and severity of flooding in coastal regions. The rate and amount of global-mean SLR is a function of the trajectory of the global mean surface temperature (GMST). Therefore, temperature stabilization targets (e.g., 1.5°C or 2°C, as from the Paris Agreement) have important implications for regulating coastal flood risk. Quantifying the differences in the impact from SLR between these and other GMST stabilization targets is necessary for assessing the benefits and harms of mitigation goals. Low-lying small island nations are particularly vulnerable to inundation and coastal flooding from SLR because building protective and resilient infrastructure may not be physically or economically feasible. For small island nations, keeping GMST below a specified threshold may be the only option for maintaining habitability. Here, we assess differences in the return levels of coastal floods for small island nations between 1.5°C, 2.0°C, and 2.5°C GMST stabilization. We employ probabilistic, localized SLR projections and long-term hourly tide gauge records to construct estimates of local flood risk. We then estimate the number of small island nations' inhabitants at risk for permanent inundation under different GMST stabilization targets.

Modelling Recycling Targets

DEFF Research Database (Denmark)

Hill, Amanda Louise; Leinikka Dall, Ole; Andersen, Frits M.

2014-01-01

Within the European Union (EU) a paradigm shift is currently occurring in the waste sector, where EU waste directives and national waste strategies are placing emphasis on resource efficiency and recycling targets. The most recent Danish resource strategy calculates a national recycling rate of 22......% for household waste, and sets an ambitious goal of a 50% recycling rate by 2020. This study integrates the recycling target into the FRIDA model to project how much waste and from which streams should be diverted from incineration to recycling in order to achieve the target. Furthermore, it discusses how...... the existing technological, organizational and legislative frameworks may affect recycling activities. The results of the analysis show that with current best practice recycling rates, the 50% recycling rate cannot be reached without recycling of household biowaste. It also shows that all Danish municipalities...

Clinical benefit of drugs targeting mitochondrial function as an adjunct to reperfusion in ST-segment elevation myocardial infarction

DEFF Research Database (Denmark)

Campo, Gianluca; Pavasini, Rita; Morciano, Giampaolo

2017-01-01

AIMS: To perform a systematic review and meta-analysis of randomized clinical trials (RCT) comparing the effectiveness of drugs targeting mitochondrial function vs. placebo in patients with ST-segment elevation myocardial infarction (STEMI) undergoing mechanical coronary reperfusion. METHODS...

Automated alignment of the Advanced Radiographic Capability (ARC) target area at the National Ignition Facility

Science.gov (United States)

Roberts, Randy S.; Awwal, Abdul A. S.; Bliss, Erlan S.; Heebner, John E.; Leach, Richard R.; Orth, Charles D.; Rushford, Michael C.; Lowe-Webb, Roger R.; Wilhelmsen, Karl C.

2015-09-01

The Advanced Radiographic Capability (ARC) at the National Ignition Facility (NIF) is a petawatt-class, short-pulse laser system designed to provide x-ray backlighting of NIF targets. ARC uses four NIF beamlines to produce eight beamlets to create a sequence of eight images of an imploding fuel capsule using backlighting targets and diagnostic instrumentation. ARC employs a front end that produces two pulses, chirps the pulses out to 2 ns, and then injects the pulses into the two halves of each of four NIF beamlines. These pulses are amplified by NIF pre- and main amplifiers and transported to compressor vessels located in the NIF target area. The pulses are then compressed and pointed into the NIF target chamber where they impinge upon an array of backlighters. The interaction of the ARC laser pulses and the backlighting material produces bursts of high-energy x-rays that illuminate an imploding fuel capsule. The transmitted x-rays are imaged by diagnostic instrumentation to produce a sequence of radiograph images. A key component of the success of ARC is the automatic alignment system that accomplishes the precise alignment of the beamlets to avoid damaging equipment and to ensure that the beamlets are directed onto the tens-of-microns scale backlighters. In this paper, we describe the ARC automatic alignment system, with emphasis on control loops used to align the beampaths. We also provide a detailed discussion of the alignment image processing, because it plays a critical role in providing beam centering and pointing information for the control loops.

Nova target experiments

International Nuclear Information System (INIS)

Drake, R.P.

1985-11-01

The Nova laser, at the Lawrence Livermore National Laboratory, provides unique opportunities for target experiments. It has unprecedented energy on target and significant flexibility. The paper presented by John Hunt described the capabilities and the status of Nova. This paper discusses plans for future experiments using Nova, and the present status of target experiments. We plan to perform high-quality physics experiments that exploit the unique capabilities of Nova. Because this is our goal, we are fielding an extensive array of well-characterized target diagnostics to measure the emissions from the target. The first section of this paper discusses the basic target diagnostics. We are also taking care to quantify the performance of the laser

Clinical targeting recombinant immunotoxins for cancer therapy

Directory of Open Access Journals (Sweden)

Li M

2017-07-01

Full Text Available Meng Li,1,* Zeng-Shan Liu,1,* Xi-Lin Liu,1,* Qi Hui,2,* Shi-Ying Lu,1 Lin-Lin Qu,1 Yan-Song Li,1 Yu Zhou,1 Hong-Lin Ren,1 Pan Hu1 1Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, China-Japan Union Hospital, The First Hospital, Jilin University, Changchun, 2School of Pharmacy, Wenzhou Medical University, Wenzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Recombinant immunotoxins (RITs are proteins that contain a toxin fused to an antibody or small molecules and are constructed by the genetic engineering technique. RITs can bind to and be internalized by cells and kill cancerous or non-cancerous cells by inhibiting protein synthesis. A wide variety of RITs have been tested against different cancers in cell culture, xenograft models, and human patients during the past several decades. RITs have shown activity in therapy of several kinds of cancers, but different levels of side effects, mainly related to vascular leak syndrome, were also observed in the treated patients. High immunogenicity of RITs limited their long-term or repeat applications in clinical cases. Recent advances in the design of immunotoxins, such as humanization of antibody fragment, PEGylation, and modification of human B- and T-cell epitopes, are overcoming the above mentioned problems, which predict the use of these immunotoxins as a potential therapeutic method to treat cancer patients. Keywords: targeted therapy, hematologic malignancies, solid tumors, vascular leak syndrome, immunogenicity 

Complete fabrication of target experimental chamber and implement initial target diagnostics to be used for the first target experiments in NDCX-1

International Nuclear Information System (INIS)

Bieniosek, F.M.; Bieniosek, F.M.; Dickinson, M.R.; Henestroza, E.; Katayanagi, T.; Jung, J.Y.; Lee, C.W.; Leitner, M.; Ni, P.; Roy, P.; Seidl, P.; Waldron, W.; Welch, D.

2008-01-01

The Heavy Ion Fusion Science Virtual National Laboratory (HIFS-VNL) has completed the fabrication of a new experimental target chamber facility for future Warm Dense Matter (WDM) experiments, and implemented initial target diagnostics to be used for the first target experiments in NDCX-1. The target chamber has been installed on the NDCX-I beamline. This achievement provides to the HIFS-VNL unique and state-of-the-art experimental capabilities in preparation for the planned target heating experiments using intense heavy ion beams

One target, different effects: a comparison of distinct therapeutic antibodies against the same targets.

Science.gov (United States)

Shim, Hyunbo

2011-10-31

To date, more than 30 antibodies have been approved worldwide for therapeutic use. While the monoclonal antibody market is rapidly growing, the clinical use of therapeutic antibodies is mostly limited to treatment of cancers and immunological disorders. Moreover, antibodies against only five targets (TNF-α, HER2, CD20, EGFR, and VEGF) account for more than 80 percent of the worldwide market of therapeutic antibodies. The shortage of novel, clinically proven targets has resulted in the development of many distinct therapeutic antibodies against a small number of proven targets, based on the premise that different antibody molecules against the same target antigen have distinct biological and clinical effects from one another. For example, four antibodies against TNF-α have been approved by the FDA -- infliximab, adalimumab, golimumab, and certolizumab pegol -- with many more in clinical and preclinical development. The situation is similar for HER2, CD20, EGFR, and VEGF, each having one or more approved antibodies and many more under development. This review discusses the different binding characteristics, mechanisms of action, and biological and clinical activities of multiple monoclonal antibodies against TNF-α, HER-2, CD20, and EGFR and provides insights into the development of therapeutic antibodies.

Clinical trials of boron neutron capture therapy [in humans] [at Beth Israel Deaconess Medical Center][at Brookhaven National Laboratory

International Nuclear Information System (INIS)

Wallace, Christine

2001-01-01

Assessment of research records of Boron Neutron Capture Therapy was conducted at Brookhaven National Laboratory and Beth Israel Deaconess Medical Center using the Code of Federal Regulations, FDA Regulations and Good Clinical Practice Guidelines. Clinical data were collected FR-om subjects' research charts, and differences in conduct of studies at both centers were examined. Records maintained at Brookhaven National Laboratory were not in compliance with regulatory standards. Beth Israel's records followed federal regulations. Deficiencies discovered at both sites are discussed in the reports

Target support for inertial confinement fusion

International Nuclear Information System (INIS)

Schultz, K.R.

1995-08-01

General Atomics (GA) plays an important industrial support role for the US Inertial Confinement Fusion (ICF) program in the area of target technology. This includes three major activities: target fabrication support, target handling systems development, and target chamber design. The work includes target fabrication for existing ICF experiments, target and target system development for future experiments, and target research and target chamber design for experiments on future machines, such as the National Ignition Facility (NIF)

Gene Dosage Analysis in a Clinical Environment: Gene-Targeted Microarrays as the Platform-of-Choice

Directory of Open Access Journals (Sweden)

Donald R. Love

2013-03-01

Full Text Available The role of gene deletion and duplication in the aetiology of disease has become increasingly evident over the last decade. In addition to the classical deletion/duplication disorders diagnosed using molecular techniques, such as Duchenne Muscular Dystrophy and Charcot-Marie-Tooth Neuropathy Type 1A, the significance of partial or whole gene deletions in the pathogenesis of a large number single-gene disorders is becoming more apparent. A variety of dosage analysis methods are available to the diagnostic laboratory but the widespread application of many of these techniques is limited by the expense of the kits/reagents and restrictive targeting to a particular gene or portion of a gene. These limitations are particularly important in the context of a small diagnostic laboratory with modest sample throughput. We have developed a gene-targeted, custom-designed comparative genomic hybridisation (CGH array that allows twelve clinical samples to be interrogated simultaneously for exonic deletions/duplications within any gene (or panel of genes on the array. We report here on the use of the array in the analysis of a series of clinical samples processed by our laboratory over a twelve-month period. The array has proven itself to be robust, flexible and highly suited to the diagnostic environment.

Management of rheumatoid arthritis in clinical practice using treat-to-target strategy: Where do we stand in the multi-ethnic Malaysia population?

Science.gov (United States)

Tan, Bee Eng; Lim, Ai Lee; Kan, Sow Lai; Lim, Chong Hong; Ng, Ying Fun; Tng, Serene Li Ching; Hassin, Nur Syakirah; Chandran, Losshenee; Hamid, Norshahida Abdul; Lee, Yvonne Yin Leng

2017-06-01

To evaluate the achievement of treat-to-target (T2T) strategy in rheumatoid arthritis (RA) and identify factors associated with failed treatment target in a public rheumatology center. A cross-sectional study was conducted from June 2015 to February 2016. RA patients with disease duration greater than 2 years and under T2T for over a year were invited to the study. Demographic, clinical data, disease activity score of 28 joints (DAS28), and clinical disease activity index (CDAI) were collected in a single routine clinic visit. Treatment target was defined as DAS28 review was performed to determine reasons of failed treatment target. A total of 371 patients were recruited and 87.1% were female. Mean age and duration of RA were 53.5 years (SD 10.3) and 9.1 years (SD 6.6), respectively. Ethnic distribution was 49% Chinese, 27% Malay, and 24% Indian. T2T was achieved in 81.7% of the cohort. Non-Chinese ethnicity, positive rheumatoid factor, and treatment with three disease modifying anti-rheumatic drugs (DMARDs) were associated with failed treatment target. After controlling for covariates, Malay ethnicity (OR 2.96; 95% CI 1.47-5.96) and treatment with three DMARDs (OR 2.14; 95% CI 1.06-4.35) were associated with failed treatment target. There was no association between age, gender, duration of RA, BMI, smoking status, anti-citrulinated cyclic peptide, and achievement of T2T. The most common reasons of failed treatment target were inability to escalate DMARDs due to side effects (18.8%), lack of biologics fund (15.6%), and persistent disease despite optimum treatment (14.1%). T2T was successfully implemented. Malay patients need aggressive treatment adaptation to achieve optimal outcome.

Why Providers Participate in Clinical Trials: Considering the National Cancer Institute’s Community Clinical Oncology Program

Science.gov (United States)

McAlearney, Ann Scheck; Song, Paula H.; Reiter, Kristin L.

2012-01-01

Background The translation of research evidence into practice is facilitated by clinical trials such as those sponsored by the National Cancer Institute’s Community Clinical Oncology Program (CCOP) that help disseminate cancer care innovations to community-based physicians and provider organizations. However, CCOP participation involves unsubsidized costs and organizational challenges that raise concerns about sustained provider participation in clinical trials. Objectives This study was designed to improve our understanding of why providers participate in the CCOP in order to inform the decision-making process of administrators, clinicians, organizations, and policy-makers considering CCOP participation. Research Methods We conducted a multi-site qualitative study of five provider organizations engaged with the CCOP. We interviewed 41 administrative and clinician key informants, asking about what motivated CCOP participation, and what benefits they associated with involvement. We deductively and inductively analyzed verbatim interview transcripts, and explored themes that emerged. Results Interviewees expressed both “altruistic” and “self-interested” motives for CCOP participation. Altruistic reasons included a desire to increase access to clinical trials and feeling an obligation to patients. Self-interested reasons included the desire to enhance reputation, and a need to integrate disparate cancer care activities. Perceived benefits largely matched expressed motives for CCOP participation, and included internal and external benefits to the organization, and quality of care benefits for both patients and participating physicians. Conclusion The motives and benefits providers attributed to CCOP participation are consistent with translational research goals, offering evidence that participation can contribute value to providers by expanding access to innovative medical care for patients in need. PMID:22925970

Implementation of a Targeted Screening Program to Detect Airflow Obstruction Suggestive of Chronic Obstructive Pulmonary Disease within a Presurgical Screening Clinic

Directory of Open Access Journals (Sweden)

Chantal Robitaille

2015-01-01

Full Text Available BACKGROUND: Targeted spirometry screening for chronic obstructive pulmonary disease (COPD has been studied in primary care and community settings. Limitations regarding availability and quality of testing remain. A targeted spirometry screening program was implemented within a presurgical screening (PSS clinic to detect undiagnosed airways disease and identify patients with COPD/asthma in need of treatment optimization.

Simulations of effusion from ISOL target/ion source systems

International Nuclear Information System (INIS)

Mustapha, B.; Nolen, J.A.

2004-01-01

Monte Carlo simulations of the low- and high-conductivity Target/Ion Source systems used at Oak Ridge National Laboratory for effusion measurements are performed. Comparisons with the corresponding experimental data for the different geometries are presented and discussed. Independent checks of the simulation using data for simple geometries and using the conductance approach well known in vacuum technology are performed. A simulation-based comparison between the low- and high-conductivity systems is also presented

Impact of Different CT Slice Thickness on Clinical Target Volume for 3D Conformal Radiation Therapy

International Nuclear Information System (INIS)

Prabhakar, Ramachandran; Ganesh, Tharmar; Rath, Goura K.; Julka, Pramod K.; Sridhar, Pappiah S.; Joshi, Rakesh C.; Thulkar, Sanjay

2009-01-01

The purpose of this study was to present the variation of clinical target volume (CTV) with different computed tomography (CT) slice thicknesses and the impact of CT slice thickness on 3-dimensional (3D) conformal radiotherapy treatment planning. Fifty patients with brain tumors were selected and CT scans with 2.5-, 5-, and 10-mm slice thicknesses were performed with non-ionic contrast enhancement. The patients were selected with tumor volume ranging from 2.54 cc to 222 cc. Three-dimensional treatment planning was performed for all three CT datasets. The target coverage and the isocenter shift between the treatment plans for different slice thickness were correlated with the tumor volume. An important observation from our study revealed that for volume 25 cc, the target underdosage was less than 6.7% for 5-mm slice thickness and 8% for 10-mm slice thickness. For 3D conformal radiotherapy treatment planning (3DCRT), a CT slice thickness of 2.5 mm is optimum for tumor volume 25 cc

Clinical Case Registries: Simultaneous Local and National Disease Registries for Population Quality Management

Science.gov (United States)

Backus, Lisa I.; Gavrilov, Sergey; Loomis, Timothy P.; Halloran, James P.; Phillips, Barbara R.; Belperio, Pamela S.; Mole, Larry A.

2009-01-01

The Department of Veterans Affairs (VA) has a system-wide, patient-centric electronic medical record system (EMR) within which the authors developed the Clinical Case Registries (CCR) to support population-centric delivery and evaluation of VA medical care. To date, the authors have applied the CCR to populations with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Local components use diagnosis codes and laboratory test results to identify patients who may have HIV or HCV and support queries on local care delivery with customizable reports. For each patient in a local registry, key EMR data are transferred via HL7 messaging to a single national registry. From 128 local registry systems, over 60,000 and 320,000 veterans in VA care have been identified as having HIV and HCV, respectively, and entered in the national database. Local and national reports covering demographics, resource usage, quality of care metrics and medication safety issues have been generated. PMID:19717794

Finding pathways to national-scale land-sector sustainability

Science.gov (United States)

Gao, Lei; Bryan, Brett A.

2017-04-01

The 17 Sustainable Development Goals (SDGs) and 169 targets under Agenda 2030 of the United Nations map a coherent global sustainability ambition at a level of detail general enough to garner consensus amongst nations. However, achieving the global agenda will depend heavily on successful national-scale implementation, which requires the development of effective science-driven targets tailored to specific national contexts and supported by strong national governance. Here we assess the feasibility of achieving multiple SDG targets at the national scale for the Australian land-sector. We scaled targets to three levels of ambition and two timeframes, then quantitatively explored the option space for target achievement under 648 plausible future environmental, socio-economic, technological and policy pathways using the Land-Use Trade-Offs (LUTO) integrated land systems model. We show that target achievement is very sensitive to global efforts to abate emissions, domestic land-use policy, productivity growth rate, and land-use change adoption behaviour and capacity constraints. Weaker target-setting ambition resulted in higher achievement but poorer sustainability outcomes. Accelerating land-use dynamics after 2030 changed the targets achieved by 2050, warranting a longer-term view and greater flexibility in sustainability implementation. Simultaneous achievement of multiple targets is rare owing to the complexity of sustainability target implementation and the pervasive trade-offs in resource-constrained land systems. Given that hard choices are needed, the land-sector must first address the essential food/fibre production, biodiversity and land degradation components of sustainability via specific policy pathways. It may also contribute to emissions abatement, water and energy targets by capitalizing on co-benefits. However, achieving targets relevant to the land-sector will also require substantial contributions from other sectors such as clean energy, food systems

Targeted Nanoparticles for Image-guided Treatment of Triple Negative Breast Cancer: Clinical Significance and Technological Advances

Science.gov (United States)

Miller-Kleinhenz, Jasmine M.; Bozeman, Erica N.

2015-01-01

Effective treatment of triple negative breast cancer (TNBC) with its aggressive tumor biology, highly heterogeneous tumor cells, and poor prognosis requires an integrated therapeutic approach that addresses critical issues in cancer therapy. Multifunctional nanoparticles with the abilities of targeted drug delivery and non-invasive imaging for monitoring drug delivery and responses to therapy, such as theranostic nanoparticles, hold great promise towards the development of novel therapeutic approaches for the treatment of TNBC using a single therapeutic platform. The biological and pathological characteristics of TNBC provide insight into several potential molecular targets for current and future nanoparticle based therapeutics. Extensive tumor stroma, highly proliferative cells, and a high rate of drug-resistance are all barriers that must be appropriately addressed in order for these nanotherapeutic platforms to be effective. Utilization of the enhanced permeability and retention (EPR) effect coupled with active targeting of cell surface receptors expressed by TNBC cells, and tumor associated endothelial cells, stromal fibroblasts and macrophages is likely to overcome such barriers to facilitate more effective drug delivery. An in depth summary of current studies investigating targeted nanoparticles in preclinical TNBC mouse and human xenograft models is presented. This review aims to outline the current status of nanotherapeutic options for TNBC patients, identification of promising molecular targets, challenges associated with the development of targeted nanotherapeutics, the research done by our group as well as others and future perspectives on the nanomedicine field and ways to translate current preclinical studies into the clinic. PMID:25966677

Study Identifies New Lymphoma Treatment Target

Science.gov (United States)

NCI researchers have identified new therapeutic targets for diffuse large B-cell lymphoma. Drugs that hit these targets are under clinical development and the researchers hope to begin testing them in clinical trials of patients with DLBCL.

The National Spallation Neutron Source Target Station.

Science.gov (United States)

Gabriel, T. A.

1997-05-01

The technologies that are being utilized to design and build a state-of-the-art high powered (>= 1 MW), short pulsed (storage ring. Many scientific and technical disciplines are required to produce a successful target station. These disciplines include engineering, remote handling, neutronics, materials, thermal hydraulics, shock analysis, etc. In the areas of engineering and remote handling special emphasis is being given to rapid and efficient assembly and disassembly of critical parts of the target station. In the neutronics area, emphasis is being given to neutron yield and pulse optimization from the moderators, and heating and activation rates throughout the station. Development of structural materials to withstand aggressive radiation environments and that are compatible with other materials is also an important area. Thermal hydraulics and shock analysis are being closely studied since large amounts of energy are being deposited in small volumes in relatively short time periods (< 1 μsec). These areas will be expanded upon in the paper.

Prostate bed target interfractional motion using RTOG consensus definitions and daily CT on rails. Does target motion differ between superior and inferior portions of the clinical target volume

International Nuclear Information System (INIS)

Verma, Vivek; Zhou, Sumin; Enke, Charles A.; Wahl, Andrew O.; Chen, Shifeng

2017-01-01

Using high-quality CT-on-rails imaging, the daily motion of the prostate bed clinical target volume (PB-CTV) based on consensus Radiation Therapy Oncology Group (RTOG) definitions (instead of surgical clips/fiducials) was studied. It was assessed whether PB motion in the superior portion of PB-CTV (SUP-CTV) differed from the inferior PB-CTV (INF-CTV). Eight pT2-3bN0-1M0 patients underwent postprostatectomy intensity-modulated radiotherapy, totaling 300 fractions. INF-CTV and SUP-CTV were defined as PB-CTV located inferior and superior to the superior border of the pubic symphysis, respectively. Daily pretreatment CT-on-rails images were compared to the planning CT in the left-right (LR), superoinferior (SI), and anteroposterior (AP) directions. Two parameters were defined: ''total PB-CTV motion'' represented total shifts from skin tattoos to RTOG-defined anatomic areas; ''PB-CTV target motion'' (performed for both SUP-CTV and INF-CTV) represented shifts from bone to RTOG-defined anatomic areas (i. e., subtracting shifts from skin tattoos to bone). Mean (± standard deviation, SD) total PB-CTV motion was -1.5 (± 6.0), 1.3 (± 4.5), and 3.7 (± 5.7) mm in LR, SI, and AP directions, respectively. Mean (± SD) PB-CTV target motion was 0.2 (±1.4), 0.3 (±2.4), and 0 (±3.1) mm in the LR, SI, and AP directions, respectively. Mean (± SD) INF-CTV target motion was 0.1 (± 2.8), 0.5 (± 2.2), and 0.2 (± 2.5) mm, and SUP-CTV target motion was 0.3 (± 1.8), 0.5 (± 2.3), and 0 (± 5.0) mm in LR, SI, and AP directions, respectively. No statistically significant differences between INF-CTV and SUP-CTV motion were present in any direction. There are no statistically apparent motion differences between SUP-CTV and INF-CTV. Current uniform planning target volume (PTV) margins are adequate to cover both portions of the CTV. (orig.) [de

Characteristics of substance abuse treatment programs providing services for HIV/AIDS, hepatitis C virus infection, and sexually transmitted infections: the National Drug Abuse Treatment Clinical Trials Network.

Science.gov (United States)

Brown, Lawrence S; Kritz, Steven Allan; Goldsmith, R Jeffrey; Bini, Edmund J; Rotrosen, John; Baker, Sherryl; Robinson, Jim; McAuliffe, Patrick

2006-06-01

Illicit drug users sustain the epidemics of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), hepatitis C (HCV), and sexually transmitted infections (STIs). Substance abuse treatment programs present a major intervention point in stemming these epidemics. As a part of the "Infections and Substance Abuse" study, established by the National Drug Abuse Treatment Clinical Trials Network, sponsored by National Institute on Drug Abuse, three surveys were developed; for treatment program administrators, for clinicians, and for state and District of Columbia health and substance abuse department administrators, capturing service availability, government mandates, funding, and other key elements related to the three infection groups. Treatment programs varied in corporate structure, source of revenue, patient census, and medical and non-medical staffing; medical services, counseling services, and staff education targeted HIV/AIDS more often than HCV or STIs. The results from this study have the potential to generate hypotheses for further health services research to inform public policy.

National Beef Quality Audit-2011: Harvest-floor assessments of targeted characteristics that affect quality and value of cattle, carcasses, and byproducts

Science.gov (United States)

The National Beef Quality Audit-2011(NBQA-2011) was conducted to assess targeted characteristics on the harvest floor that affect the quality and value of cattle, carcasses, and byproducts. Survey teams evaluated approximately 18,000 cattle/carcasses between May and November 2011 in 8 beef processin...

Obstacles to the implementation of the treat-to-target strategy for rheumatoid arthritis in clinical practice in Japan.

Science.gov (United States)

Kaneko, Yuko; Koike, Takao; Oda, Hiromi; Yamamoto, Kazuhiko; Miyasaka, Nobuyuki; Harigai, Masayoshi; Yamanaka, Hisashi; Ishiguro, Naoki; Tanaka, Yoshiya; Takeuchi, Tsutomu

2015-01-01

To clarify the obstacles preventing the implementation of the treat-to-target (T2T) strategy for rheumatoid arthritis (RA) in clinical practice. A total of 301 rheumatologists in Japan completed a questionnaire. In the first section, participants were indirectly questioned on the implementation of basic components of T2T, and in the second section, participants were directly questioned on their level of agreement and application. Although nearly all participants set treatment targets for the majority of RA patients with moderate to high disease activity, the proportion who set clinical remission as their target was 59%, with only 45% of these using composite measures. The proportion of participants who monitored X-rays and Health Assessment Questionnaires for all their patients was 44% and 14%, respectively. The proportion of participants who did not discuss treatment strategies was 44%, with approximately half of these reasoning that this was due to a proportion of patients having a lack of understanding of the treatment strategy or inability to make decisions. When participants were directly questioned, there was a high level of agreement with the T2T recommendations. Although there was a high level of agreement with the T2T recommendations, major obstacles preventing its full implementation still remain.

Radial displacement of clinical target volume in node negative head and neck cancer

International Nuclear Information System (INIS)

Jeon, Wan; Wu, Hong Gyun; Song, Sang Hyuk; Kim, Jung In

2012-01-01

To evaluate the radial displacement of clinical target volume in the patients with node negative head and neck (H and N) cancer and to quantify the relative positional changes compared to that of normal healthy volunteers. Three node-negative H and N cancer patients and fi ve healthy volunteers were enrolled in this study. For setup accuracy, neck thermoplastic masks and laser alignment were used in each of the acquired computed tomography (CT) images. Both groups had total three sequential CT images in every two weeks. The lymph node (LN) level of the neck was delineated based on the Radiation Therapy Oncology Group (RTOG) consensus guideline by one physician. We use the second cervical vertebra body as a reference point to match each CT image set. Each of the sequential CT images and delineated neck LN levels were fused with the primary image, then maximal radial displacement was measured at 1.5 cm intervals from skull base (SB) to caudal margin of LN level V, and the volume differences at each node level were quantified. The mean radial displacements were 2.26 (±1.03) mm in the control group and 3.05 (±1.97) in the H and N cancer patients. There was a statistically significant difference between the groups in terms of the mean radial displacement (p = 0.03). In addition, the mean radial displacement increased with the distance from SB. As for the mean volume differences, there was no statistical significance between the two groups. This study suggests that a more generous radial margin should be applied to the lower part of the neck LN for better clinical target coverage and dose delivery.

[Clinical governance and patient safety culture in clinical laboratories in the Spanish National Health System].

Science.gov (United States)

Giménez-Marín, Á; Rivas-Ruiz, F

To conduct a situational analysis of patient safety culture in public laboratories in the Spanish National Health System and to determine the clinical governance variables that most strongly influence patient safety. A descriptive cross-sectional study was carried out, in which a Survey of Patient Safety in Clinical Laboratories was addressed to workers in 26 participating laboratories. In this survey, which consisted of 45 items grouped into 6 areas, scores were assigned on a scale from 0 to 100 (where 0 is the lowest perception of patient safety). Laboratory managers were asked specific questions about quality management systems and technology. The mean scores for the 26 participating hospitals were evaluated, and the following results observed: in 4of the 6areas, the mean score was higher than 70 points. In the third area (equipment and resources) and the fourth area (working conditions), the scores were lower than 60 points. Every hospital had a digital medical record system. This 100% level of provision was followed by that of an electronic request management system, which was implemented in 82.6% of the hospitals. The results obtained show that the culture of security is homogeneous and of high quality in health service laboratories, probably due to the steady improvement observed. However, in terms of clinical governance, there is still some way to go, as shown by the presence of weaknesses in crucial dimensions of safety culture, together with variable levels of implementation of fail-safe technologies and quality management systems. Copyright © 2017 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

How Public Health Nurses Identify and Intervene in Child Maltreatment Based on the National Clinical Guideline

Directory of Open Access Journals (Sweden)

Paavilainen Eija

2014-01-01

Full Text Available Objectives. To describe how Finnish public health nurses identify and intervene in child maltreatment and how they implement the National Clinical Guideline in their work. Design and Sample. Cross-sectional survey of 367 public health nurses in Finland. Measures. A web-based questionnaire developed based on the content areas of the guideline: identifying, intervening, and implementing. Results. The respondents reported they identify child maltreatment moderately (mean 3.38, intervene in it better (4.15, and implement the guideline moderately (3.43, scale between 1 and 6. Those with experience of working with maltreated children reported they identify them better P<0.001, intervene better P<0.001, and implement the guideline better P<0.001 than those with no experience. This difference was also found for those who were aware of the guideline, had read it, and participated in training on child maltreatment, as compared to those who were not aware of the guideline, had not read it, or had not participated in such training. Conclusions. The public health nurses worked quite well with children who had experienced maltreatment and families. However, the results point out several developmental targets for increasing training on child maltreatment, for devising recommendations for child maltreatment, and for applying these recommendations systematically in practice.

Isotope materials availability and services for target production at the Oak Ridge National Laboratory

International Nuclear Information System (INIS)

Ratledge, J.E.; Dahl, T.L.; Ottinger, C.L.; Aaron, W.S.; Adair, H.L.

1987-01-01

Materials available through the Isotope Distribution Program include separated stable isotopes, byproduct radioisotopes, and research quantities of source and special nuclear materials. Isotope products are routinely available in the forms listed in the product description section of the Isotopes Products and Services Catalog distributed by the Oak Ridge National Laboratory (ORNL). Different forms can be provided in some cases, usually at additional cost. Routinely available services include cyclotron target irradiations, fabrication of special physical forms, source encapsulation, ion implantation, and special purifications. Materials and services that are not offered as part of the routine distribution program may be made available from commercial sources in the United States. Specific forms of isotopic research materials include thin films and foils for use as accelerator targets, metal or other compounds in the form of bars or wires, and metal foils. Methods of fabrication include evaporation, sputtering, rolling, electrolytic deposition, pressing, sintering, and casting. High-purity metal forms of plutonium, americium, and curium are prepared by vacuum reduction/distillation. Both fissionable and nonfissionable neutron dosimeters are prepared for determining the neutron energy spectra, flux, and fluence at various locations within a reactor. Details on what materials are available and how the materials and related services can be obtained from ORNL are described. (orig.)

Clinical requirements and accelerator concepts for BNCT

International Nuclear Information System (INIS)

Ludewigt, B.A.; Bleuel, D.L.; Chu, W.T.; Donahue, R.J.; Kwan, J.; Leung, K.N.; Reginato, L.L.; Wells, R.P.

1997-05-01

Accelerator-based neutron sources are an attractive alternative to nuclear reactors for providing epithermal neutron beams for Boron Neutron Capture Therapy. Based on clinical requirements and neutronics modeling the use of proton and deuteron induced reactions in 7 Li and 9 Be targets has been compared. Excellent epithermal neutron beams can be produced via the 7 Li(p,n) 7 Be reaction at proton energies of ∼2.5 MeV. An electrostatic quadrupole accelerator and a lithium target, which can deliver and handle 2.5 MeV protons at beam currents up to 50 mA, are under development for an accelerator-based BNCT facility at the Lawrence Berkeley National Laboratory

Service impact of a national clinical leadership development programme: findings from a qualitative study.

Science.gov (United States)

Fealy, Gerard M; McNamara, Martin S; Casey, Mary; O'Connor, Tom; Patton, Declan; Doyle, Louise; Quinlan, Christina

2015-04-01

The study reported here was part of a larger study, which evaluated a national clinical leadership development programme with reference to resources, participant experiences, participant outcomes and service impact. The aim of the present study was to evaluate the programme's service impact. Clinical leadership development develops competencies that are expressed in context. The outcomes of clinical leadership development occur at individual, departmental and organisational levels. The methods used to evaluate the service impact were focus groups, group interviews and individual interviews. Seventy participants provided data in 18 separate qualitative data collection events. The data contained numerous accounts of service development activities, initiated by programme participants, which improved service and/or improved the culture of the work setting. Clinical leadership development programmes that incorporate a deliberate service impact element can result in identifiable positive service outcomes. The nuanced relationship between leader development and service development warrants further investigation. This study demonstrates that clinical leadership development can impact on service in distinct and identifiable ways. Clinical leadership development programmes should focus on the setting in which the leadership competencies will be demonstrated. © 2013 John Wiley & Sons Ltd.

National survey of clinical communication assessment in medical education in the United Kingdom (UK).

Science.gov (United States)

Laidlaw, Anita; Salisbury, Helen; Doherty, Eva M; Wiskin, Connie

2014-01-13

All medical schools in the UK are required to be able to provide evidence of competence in clinical communication in their graduates. This is usually provided by summative assessment of clinical communication, but there is considerable variation in how this is carried out. This study aimed to gain insight into the current assessment of clinical communication in UK medical schools. The survey was sent via e-mail to communication leads who then were asked to consult with all staff within their medical school involved in the assessment of communication. Results were obtained from 27 out of 33 schools (response rate 82%) and a total of 34 courses. The average number of assessments per year was 2.4 (minimum 0, maximum 10). The Objective Structured Clinical Exam (OSCE) was the most commonly used method of assessment (53%). Other assessments included MCQ and workplace based assessments. Only nine courses used a single method of assessment. Issues raised included, logistics and costs of assessing mainly by OSCE, the robustness and reliability of such exams and integration with other clinical skills. It is encouraging that a variety of assessment methods are being used within UK medical schools and that these methods target different components of clinical communication skills acquisition.

Clinical and radiographic outcome of a treat-to-target strategy using methotrexate and intra-articular glucocorticoids with or without adalimumab induction

DEFF Research Database (Denmark)

Hørslev-Petersen, K; Hetland, M L; Ørnbjerg, L M

2015-01-01

OBJECTIVES: To study clinical and radiographic outcomes after withdrawing 1 year's adalimumab induction therapy for early rheumatoid arthritis (eRA) added to a methotrexate and intra-articular triamcinolone hexacetonide treat-to-target strategy (NCT00660647). METHODS: Disease-modifying antirheuma......OBJECTIVES: To study clinical and radiographic outcomes after withdrawing 1 year's adalimumab induction therapy for early rheumatoid arthritis (eRA) added to a methotrexate and intra-articular triamcinolone hexacetonide treat-to-target strategy (NCT00660647). METHODS: Disease.......12). Erosive progression (Δerosion score (ES)/year) was year 1:0.57/0.06 (p=0.02); year 2:0.38/0.05 (p=0.005). Proportion of patients without erosive progression (ΔES≤0) was year 1: 59%/76% (p=0.03); year 2:64%/79% (p=0.04). CONCLUSIONS: An aggressive triamcinolone and synthetic DMARD treat-to-target strategy...... was (re)initiated in 12/12 patients and cumulative triamcinolone dose was 160/120 mg (p=0.15). The treatment target (disease activity score, 4 variables, C-reactive protein (DAS28CRP) ≤3.2 or DAS28>3.2 without swollen joints) was achieved at all visits in ≥85% of patients in year 2; remission rates were...

An intensive nurse-led, multi-interventional clinic is more successful in achieving vascular risk reduction targets than standard diabetes care.

LENUS (Irish Health Repository)

MacMahon Tone, J

2009-06-01

The aim of this research was to determine whether an intensive, nurse-led clinic could achieve recommended vascular risk reduction targets in patients with type 2 diabetes as compared to standard diabetes management.

A national clinical quality program for Veterans Affairs catheterization laboratories (from the Veterans Affairs clinical assessment, reporting, and tracking program).

Science.gov (United States)

Maddox, Thomas M; Plomondon, Mary E; Petrich, Megan; Tsai, Thomas T; Gethoffer, Hans; Noonan, Gregory; Gillespie, Brian; Box, Tamara; Fihn, Stephen D; Jesse, Robert L; Rumsfeld, John S

2014-12-01

A "learning health care system", as outlined in a recent Institute of Medicine report, harnesses real-time clinical data to continuously measure and improve clinical care. However, most current efforts to understand and improve the quality of care rely on retrospective chart abstractions complied long after the provision of clinical care. To align more closely with the goals of a learning health care system, we present the novel design and initial results of the Veterans Affairs (VA) Clinical Assessment, Reporting, and Tracking (CART) program-a national clinical quality program for VA cardiac catheterization laboratories that harnesses real-time clinical data to support clinical care and quality-monitoring efforts. Integrated within the VA electronic health record, the CART program uses a specialized software platform to collect real-time patient and procedural data for all VA patients undergoing coronary procedures in VA catheterization laboratories. The program began in 2005 and currently contains data on 434,967 catheterization laboratory procedures, including 272,097 coronary angiograms and 86,481 percutaneous coronary interventions, performed by 801 clinicians on 246,967 patients. We present the initial data from the CART program and describe 3 quality-monitoring programs that use its unique characteristics-procedural and complications feedback to individual labs, coronary device surveillance, and major adverse event peer review. The VA CART program is a novel approach to electronic health record design that supports clinical care, quality, and safety in VA catheterization laboratories. Its approach holds promise in achieving the goals of a learning health care system. Published by Elsevier Inc.

Targeted nanoparticles for image-guided treatment of triple-negative breast cancer: clinical significance and technological advances.

Science.gov (United States)

Miller-Kleinhenz, Jasmine M; Bozeman, Erica N; Yang, Lily

2015-01-01

Effective treatment of triple-negative breast cancer (TNBC) with its aggressive tumor biology, highly heterogeneous tumor cells, and poor prognosis requires an integrated therapeutic approach that addresses critical issues in cancer therapy. Multifunctional nanoparticles with the abilities of targeted drug delivery and noninvasive imaging for monitoring drug delivery and responses to therapy, such as theranostic nanoparticles, hold great promise toward the development of novel therapeutic approaches for the treatment of TNBC using a single therapeutic platform. The biological and pathological characteristics of TNBC provide insight into several potential molecular targets for current and future nanoparticle-based therapeutics. Extensive tumor stroma, highly proliferative cells, and a high rate of drug resistance are all barriers that must be appropriately addressed in order for these nanotherapeutic platforms to be effective. Utilization of the enhanced permeability and retention effect coupled with active targeting of cell surface receptors expressed by TNBC cells, and tumor-associated endothelial cells, stromal fibroblasts, and macrophages is likely to overcome such barriers to facilitate more effective drug delivery. An in-depth summary of current studies investigating targeted nanoparticles in preclinical TNBC mouse and human xenograft models is presented. This review aims to outline the current status of nanotherapeutic options for TNBC patients, identification of promising molecular targets, challenges associated with the development of targeted nanotherapeutics, the research done by our group as well as by others, and future perspectives on the nanomedicine field and ways to translate current preclinical studies into the clinic. © 2015 Wiley Periodicals, Inc.

Target validation: linking target and chemical properties to desired product profile.

Science.gov (United States)

Wyatt, Paul G; Gilbert, Ian H; Read, Kevin D; Fairlamb, Alan H

2011-01-01

The discovery of drugs is a lengthy, high-risk and expensive business taking at least 12 years and is estimated to cost upwards of US$800 million for each drug to be successfully approved for clinical use. Much of this cost is driven by the late phase clinical trials and therefore the ability to terminate early those projects destined to fail is paramount to prevent unwanted costs and wasted effort. Although neglected diseases drug discovery is driven more by unmet medical need rather than financial considerations, the need to minimise wasted money and resources is even more vital in this under-funded area. To ensure any drug discovery project is addressing the requirements of the patients and health care providers and delivering a benefit over existing therapies, the ideal attributes of a novel drug needs to be pre-defined by a set of criteria called a target product profile. Using a target product profile the drug discovery process, clinical study design, and compound characteristics can be defined all the way back through to the suitability or druggability of the intended biochemical target. Assessment and prioritisation of the most promising targets for entry into screening programmes is crucial for maximising chances of success.

Clinical proteomics

DEFF Research Database (Denmark)

Albrethsen, Jakob; Frederiksen, Hanne; Johannsen, Trine Holm

2018-01-01

Clinical proteomics aims to deliver cost-effective multiplexing of potentially hundreds of diagnostic proteins, including distinct protein isoforms. The analytical strategy known as targeted proteomics is particularly promising because it is compatible with robust mass spectrometry (MS)-platforms...... standards and calibrants. The present challenge is to examine if targeted proteomics of IGF-I can truly measure up to the routine performance that must be expected from a clinical testing platform.......Clinical proteomics aims to deliver cost-effective multiplexing of potentially hundreds of diagnostic proteins, including distinct protein isoforms. The analytical strategy known as targeted proteomics is particularly promising because it is compatible with robust mass spectrometry (MS......)-platforms already implemented in many clinical laboratories for routine quantitation of small molecules (i.e. uHPLC coupled to triple-quadrupole MS). Progress in targeted proteomics of circulating insulin-like growth factor 1 (IGF-I) have provided valuable insights about tryptic peptides, transitions, internal...

Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress

NARCIS (Netherlands)

Lammers, Twan Gerardus Gertudis Maria; Kiessling, F.; Hennink, W.E.; Storm, Gerrit

2012-01-01

Abstract Many different systems and strategies have been evaluated for drug targeting to tumors over the years. Routinely used systems include liposomes, polymers, micelles, nanoparticles and antibodies, and examples of strategies are passive drug targeting, active drug targeting to cancer cells,

Year-End Clinic Handoffs: A National Survey of Academic Internal Medicine Programs.

Science.gov (United States)

Phillips, Erica; Harris, Christina; Lee, Wei Wei; Pincavage, Amber T; Ouchida, Karin; Miller, Rachel K; Chaudhry, Saima; Arora, Vineet M

2017-06-01

While there has been increasing emphasis and innovation nationwide in training residents in inpatient handoffs, very little is known about the practice and preparation for year-end clinic handoffs of residency outpatient continuity practices. Thus, the latter remains an identified, yet nationally unaddressed, patient safety concern. The 2014 annual Association of Program Directors in Internal Medicine (APDIM) survey included seven items for assessing the current year-end clinic handoff practices of internal medicine residency programs throughout the country. Nationwide survey. All internal medicine program directors registered with APDIM. Descriptive statistics of programs and tools used to formulate a year-end handoff in the ambulatory setting, methods for evaluating the process, patient safety and quality measures incorporated within the process, and barriers to conducting year-end handoffs. Of the 361 APDIM member programs, 214 (59%) completed the Transitions of Care Year-End Clinic Handoffs section of the survey. Only 34% of respondent programs reported having a year-end ambulatory handoff system, and 4% reported assessing residents for competency in this area. The top three barriers to developing a year-end handoff system were insufficient overlap between graduating and incoming residents, inability to schedule patients with new residents in advance, and time constraints for residents, attendings, and support staff. Most internal medicine programs do not have a year-end clinic handoff system in place. Greater attention to clinic handoffs and resident assessment of this care transition is needed.

Depression screening with patient-targeted feedback in cardiology: DEPSCREEN-INFO randomised clinical trial.

Science.gov (United States)

Löwe, Bernd; Blankenberg, Stefan; Wegscheider, Karl; König, Hans-Helmut; Walter, Dirk; Murray, Alexandra M; Gierk, Benjamin; Kohlmann, Sebastian

2017-02-01

International guidelines advocate depression screening in patients with coronary heart disease (CHD) and other chronic illnesses, but evidence is lacking. To test the differential efficacy of written patient-targeted feedback v. no written patient feedback after depression screening. Patients with CHD or hypertension from three cardiology settings were randomised and screened for depression (ClinicalTrials.gov Identifier: NCT01879111). Compared with the control group, where only cardiologists received written feedback, in the intervention group both cardiologists and patients received written feedback regarding depression status. Depression severity was measured 1 month (primary outcome) and 6 months after screening. The control group (n = 220) and the patient-feedback group (n = 155) did not differ in depression severity 1 month after screening. Six months after screening, the patient-feedback group showed significantly greater improvements in depression severity and was twice as likely to seek information about depression compared with the control group. Patient-targeted feedback in addition to screening has a significant but small effect on depression severity after 6 months and may encourage patients to take an active role in the self-management of depression. © The Royal College of Psychiatrists 2017.

Radiation effects on active camera electronics in the target chamber at the National Ignition Facility

Science.gov (United States)

Dayton, M.; Datte, P.; Carpenter, A.; Eckart, M.; Manuel, A.; Khater, H.; Hargrove, D.; Bell, P.

2017-08-01

The National Ignition Facility's (NIF) harsh radiation environment can cause electronics to malfunction during high-yield DT shots. Until now there has been little experience fielding electronic-based cameras in the target chamber under these conditions; hence, the performance of electronic components in NIF's radiation environment was unknown. It is possible to purchase radiation tolerant devices, however, they are usually qualified for radiation environments different to NIF, such as space flight or nuclear reactors. This paper presents the results from a series of online experiments that used two different prototype camera systems built from non-radiation hardened components and one commercially available camera that permanently failed at relatively low total integrated dose. The custom design built in Livermore endured a 5 × 1015 neutron shot without upset, while the other custom design upset at 2 × 1014 neutrons. These results agreed with offline testing done with a flash x-ray source and a 14 MeV neutron source, which suggested a methodology for developing and qualifying electronic systems for NIF. Further work will likely lead to the use of embedded electronic systems in the target chamber during high-yield shots.

A national survey of clinical pharmacy services in county hospitals in China.

Science.gov (United States)

Yao, Dongning; Xi, Xiaoyu; Huang, Yuankai; Hu, Hao; Hu, Yuanjia; Wang, Yitao; Yao, Wenbing

2017-01-01

Clinical pharmacy is not only a medical science but also an elaborate public health care system firmly related to its subsystems of education, training, qualification authentication, scientific research, management, and human resources. China is a developing country with a tremendous need for improvements in the public health system, including the clinical pharmacy service system. The aim of this research was to evaluate the infrastructure and personnel qualities of clinical pharmacy services in China. Public county hospitals in China. A national survey of clinical pharmacists in county hospitals was conducted. It was sampled through a stratified sampling strategy. Responses were analyzed using descriptive and inferential statistics. The main outcome measures include the coverage of clinical pharmacy services, the overall staffing of clinical pharmacists, the software and hardware of clinical pharmacy services, the charge mode of clinical pharmacy services, and the educational background, professional training acquisition, practical experience, and entry path of clinical pharmacists. The overall coverage of clinical pharmacy services on both the department scale (median = 18.25%) and the patient scale (median = 15.38%) does not meet the 100% coverage that is required by the government. In 57.73% of the sample hospitals, the staffing does not meet the requirement, and the size of the clinical pharmacist group is smaller in larger hospitals. In addition, 23.4% of the sample hospitals do not have management rules for the clinical pharmacists, and 43.1% do not have rational drug use software, both of which are required by the government. In terms of fees, 89.9% of the sample hospitals do not charge for the services. With regard to education, 8.5% of respondents are with unqualified degree, and among respondents with qualified degree, 37.31% are unqualified in the major; 43% of respondents lack the clinical pharmacist training required by the government. Most

40 CFR 35.9020 - Planning targets.

Science.gov (United States)

2010-07-01

... STATE AND LOCAL ASSISTANCE Financial Assistance for the National Estuary Program § 35.9020 Planning targets. The EPA Assistant Administrator for Water develops planning targets each year to help each... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Planning targets. 35.9020 Section 35...

Laser-Plasma Interactions in Drive Campaign targets on the National Ignition Facility

International Nuclear Information System (INIS)

Hinkel, D E; Callahan, D A; Moody, J D; Amendt, P A; Lasinski, B F; MacGowan, B J; Meeker, D; Michel, P A; Ralph, J; Rosen, M D; Ross, J S; Schneider, M B; Storm, E; Strozzi, D J; Williams, E A

2016-01-01

The Drive campaign [D A Callahan et al., this conference] on the National Ignition Facility (NIF) laser [E. I. Moses, R. N. Boyd, B. A. Remington, C. J. Keane, R. Al-Ayat, Phys. Plasmas 16, 041006 (2009)] has the focused goal of understanding and optimizing the hohlraum for ignition. Both the temperature and symmetry of the radiation drive depend on laser and hohlraum characteristics. The drive temperature depends on the coupling of laser energy to the hohlraum, and the symmetry of the drive depends on beam-to-beam interactions that result in energy transfer [P. A. Michel, S. H. Glenzer, L. Divol, et al, Phys. Plasmas 17, 056305 (2010).] within the hohlraum. To this end, hohlraums are being fielded where shape (rugby vs. cylindrical hohlraums), gas fill composition (neopentane at room temperature vs. cryogenic helium), and gas fill density (increase of ∼ 150%) are independently changed. Cylindrical hohlraums with higher gas fill density show improved inner beam propagation, as should rugby hohlraums, because of the larger radius over the capsule (7 mm vs. 5.75 mm in a cylindrical hohlraum). Energy coupling improves in room temperature neopentane targets, as well as in hohlraums at higher gas fill density. In addition cross-beam energy transfer is being addressed directly by using targets that mock up one end of a hohlraum, but allow observation of the laser beam uniformity after energy transfer. Ideas such as splitting quads into “doublets” by re-pointing the right and left half of quads are also being pursued. LPI results of the Drive campaign will be summarized, and analyses of future directions presented. (paper)

20-20-20: the target of European energy policy

International Nuclear Information System (INIS)

Clo, R.; Verde, S.

2007-01-01

The last Spring European Council set ambitious targets in its new EU energy policy. Reaching these objectives is far from going without saying and without hidden dangers, if the EU aims at these targets uncritically, national and European energy systems will be exposed to additional risks and problems. Hence, the critical issues must be born in mind negotiating national targets in Brussels [it

Clinical roundtable monograph: CD30 in lymphoma: its role in biology, diagnostic testing, and targeted therapy.

Science.gov (United States)

Sotomayor, Eduardo M; Young, Ken H; Younes, Anas

2014-04-01

CD30, a member of the tumor necrosis factor receptor superfamily, is a transmembrane glycoprotein receptor consisting of an extracellular domain, a transmembrane domain, and an intracellular domain. CD30 has emerged as an important molecule in the field of targeted therapy because its expression is generally restricted to specific disease types and states. The major cancers with elevated CD30 expression include Hodgkin lymphoma and anaplastic large T-cell lymphoma, and CD30 expression is considered essential to the differential diagnosis of these malignancies. Most commonly, CD30 expression is detected and performed by immunohistochemical staining of biopsy samples. Alternatively, flow cytometry analysis has also been developed for fresh tissue and cell aspiration specimens, including peripheral blood and bone marrow aspirate. Over the past several years, several therapeutic agents were developed to target CD30, with varying success in clinical trials. A major advance in the targeting of CD30 was seen with the development of the antibody-drug conjugate brentuximab vedotin, which consists of the naked anti-CD30 antibody SGN-30 conjugated to the synthetic antitubulin agent monomethyl auristatin E. In 2011, brentuximab vedotin was approved by the US Food and Drug Administration for use in Hodgkin lymphoma and anaplastic large cell lymphoma based on clinical trial data showing high response rates in these indications. Ongoing trials are examining brentuximab vedotin after autologous stem cell transplantation, as part of chemotherapy combination regimens, and in other CD30-expressing malignancies, including primary mediastinal large B-cell lymphomas, diffuse large B-cell lymphoma, lymphoma positive for Epstein-Barr virus, peripheral T-cell lymphoma not otherwise specified, and cutaneous anaplastic large cell lymphoma.

Spallation source neutron target systems

International Nuclear Information System (INIS)

Russell, G.; Brown, R.; Collier, M.; Donahue, J.

1996-01-01

This is the final report for a two-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The project sought to design a next-generation spallation source neutron target system for the Manuel Lujan, Jr., Neutron Scattering Center (LANSCE) at Los Alamos. It has been recognized for some time that new advanced neutron sources are needed in the US if the country is to maintain a competitive position in several important scientific and technological areas. A recent DOE panel concluded that the proposed Advanced Neutron Source (a nuclear reactor at Oak Ridge National Laboratory) and a high-power pulsed spallation source are both needed in the near future. One of the most technically challenging designs for a spallation source is the target station itself and, more specifically, the target-moderator-reflector arrangement. Los Alamos has demonstrated capabilities in designing, building, and operating high-power spallation-neutron-source target stations. Most of the new design ideas proposed worldwide for target system design for the next generation pulsed spallation source have either been conceived and implemented at LANSCE or proposed by LANSCE target system designers. These concepts include split targets, flux-trap moderators, back scattering and composite moderators, and composite reflectors

Novel targeted agents for gastric cancer

Directory of Open Access Journals (Sweden)

Liu Lian

2012-06-01

Full Text Available Abstract Contemporary advancements have had little impact on the treatment of gastric cancer (GC, the world’s second highest cause of cancer death. Agents targeting human epidermal growth factor receptor mediated pathways have been a common topic of contemporary cancer research, including monoclonal antibodies (mAbs and receptor tyrosine kinase inhibitors (TKIs. Trastuzumab is the first target agent evidencing improvements in overall survival in HER2-positive (human epidermal growth factor receptor 2 gastric cancer patients. Agents targeting vascular epithelial growth factor (VEGF, mammalian target of rapamycin (mTOR, and other biological pathways are also undergoing clinical trials, with some marginally positive results. Effective targeted therapy requires patient selection based on predictive molecular biomarkers. Most phase III clinical trials are carried out without patient selection; therefore, it is hard to achieve personalized treatment and to monitor patient outcome individually. The trend for future clinical trials requires patient selection methods based on current understanding of GC biology with the application of biomarkers.

National questionnaire study on clinical ICT systems proofs: physicians suffer from poor usability.

Science.gov (United States)

Viitanen, Johanna; Hyppönen, Hannele; Lääveri, Tinja; Vänskä, Jukka; Reponen, Jarmo; Winblad, Ilkka

2011-10-01

In the health informatics field, usability studies typically focus on evaluating a single information system and involve a rather small group of end-users. However, little is known about the usability of clinical information and communication technology (ICT) environment in which healthcare professionals work daily. This paper aims at contributing to usability research and user-oriented development of healthcare technologies with three objectives: inform researchers and practitioners about the current state of usability of clinical ICT systems, increase the understanding of usability aspects specific for clinical context, and encourage a more holistic approach on studying usability issues in health informatics field. A national web questionnaire study was conducted in Finland in spring 2010 with 3929 physicians actively working in patient care. For the purposes of the study, we described three dimensions of clinical ICT system usability that reflect the physicians' viewpoint on system usage: (1) compatibility between clinical ICT systems and physicians' tasks, (2) ICT support for information exchange, communication and collaboration in clinical work, and (3) interoperability and reliability. The dimensions derive from the definitions of usability and clinical context of use analysis, and reflect the ability of ICT systems to have a positive impact on patient care by supporting physicians in achieving their goals with a pleasant user experience. The research data incorporated 32 statements with a five-point Likert-scale on physicians' experiences on usability of their currently used ICT systems and a summative question about school grade given to electronic health record (EHR) systems. Physicians' estimates of their EHR systems were very critical. With the rating scale from 4 or fail to 10 or excellent, the average of the grades varied from 6.1 to 8.4 dependent on the kind of facility the physician is working. Questionnaire results indicated several usability

Mentoring, coaching and action learning: interventions in a national clinical leadership development programme.

Science.gov (United States)

McNamara, Martin S; Fealy, Gerard M; Casey, Mary; O'Connor, Tom; Patton, Declan; Doyle, Louise; Quinlan, Christina

2014-09-01

To evaluate mentoring, coaching and action learning interventions used to develop nurses' and midwives' clinical leadership competencies and to describe the programme participants' experiences of the interventions. Mentoring, coaching and action learning are effective interventions in clinical leadership development and were used in a new national clinical leadership development programme, introduced in Ireland in 2011. An evaluation of the programme focused on how participants experienced the interventions. A qualitative design, using multiple data sources and multiple data collection methods. Methods used to generate data on participant experiences of individual interventions included focus groups, individual interviews and nonparticipant observation. Seventy participants, including 50 programme participants and those providing the interventions, contributed to the data collection. Mentoring, coaching and action learning were positively experienced by participants and contributed to the development of clinical leadership competencies, as attested to by the programme participants and intervention facilitators. The use of interventions that are action-oriented and focused on service development, such as mentoring, coaching and action learning, should be supported in clinical leadership development programmes. Being quite different to short attendance courses, these interventions require longer-term commitment on the part of both individuals and their organisations. In using mentoring, coaching and action learning interventions, the focus should be on each participant's current role and everyday practice and on helping the participant to develop and demonstrate clinical leadership skills in these contexts. © 2014 John Wiley & Sons Ltd.

Enteric Glial Cells: A New Frontier in Neurogastroenterology and Clinical Target for Inflammatory Bowel Diseases.

Science.gov (United States)

Ochoa-Cortes, Fernando; Turco, Fabio; Linan-Rico, Andromeda; Soghomonyan, Suren; Whitaker, Emmett; Wehner, Sven; Cuomo, Rosario; Christofi, Fievos L

2016-02-01

The word "glia" is derived from the Greek word "γλoια," glue of the enteric nervous system, and for many years, enteric glial cells (EGCs) were believed to provide mainly structural support. However, EGCs as astrocytes in the central nervous system may serve a much more vital and active role in the enteric nervous system, and in homeostatic regulation of gastrointestinal functions. The emphasis of this review will be on emerging concepts supported by basic, translational, and/or clinical studies, implicating EGCs in neuron-to-glial (neuroglial) communication, motility, interactions with other cells in the gut microenvironment, infection, and inflammatory bowel diseases. The concept of the "reactive glial phenotype" is explored as it relates to inflammatory bowel diseases, bacterial and viral infections, postoperative ileus, functional gastrointestinal disorders, and motility disorders. The main theme of this review is that EGCs are emerging as a new frontier in neurogastroenterology and a potential therapeutic target. New technological innovations in neuroimaging techniques are facilitating progress in the field, and an update is provided on exciting new translational studies. Gaps in our knowledge are discussed for further research. Restoring normal EGC function may prove to be an efficient strategy to dampen inflammation. Probiotics, palmitoylethanolamide (peroxisome proliferator-activated receptor-α), interleukin-1 antagonists (anakinra), and interventions acting on nitric oxide, receptor for advanced glycation end products, S100B, or purinergic signaling pathways are relevant clinical targets on EGCs with therapeutic potential.

[Resistance to target-based therapy and its circumvention].

Science.gov (United States)

Nishio, Kazuto

2004-07-01

Intrinsic and acquired resistance to molecular target therapy critically limits the outcome of cancer treatments. Target levels including quantitative and gene alteration should be determinants for the resistance. Downstream of the target molecules, drug metabolism, and drug transport influences the tumor sensitivity to molecular target therapy. The mechanisms of resistance to antibody therapy have not been fully clarified. Correlative clinical studies using these biomarkers of resistance are extremely important for circumvention of clinical resistance to target based therapy.

National direct-drive program on OMEGA and the National Ignition Facility

Science.gov (United States)

Goncharov, V. N.; Regan, S. P.; Campbell, E. M.; Sangster, T. C.; Radha, P. B.; Myatt, J. F.; Froula, D. H.; Betti, R.; Boehly, T. R.; Delettrez, J. A.; Edgell, D. H.; Epstein, R.; Forrest, C. J.; Glebov, V. Yu; Harding, D. R.; Hu, S. X.; Igumenshchev, I. V.; Marshall, F. J.; McCrory, R. L.; Michel, D. T.; Seka, W.; Shvydky, A.; Stoeckl, C.; Theobald, W.; Gatu-Johnson, M.

2017-01-01

A major advantage of the laser direct-drive (DD) approach to ignition is the increased fraction of laser drive energy coupled to the hot spot and relaxed hot-spot requirements for the peak pressure and convergence ratios relative to the indirect-drive approach at equivalent laser energy. With the goal of a successful ignition demonstration using DD, the recently established national strategy has several elements and involves multiple national and international institutions. These elements include the experimental demonstration on OMEGA cryogenic implosions of hot-spot conditions relevant for ignition at MJ-scale energies available at the National Ignition Facility (NIF) and developing an understanding of laser-plasma interactions and laser coupling using DD experiments on the NIF. DD designs require reaching central stagnation pressures in excess of 100 Gbar. The current experiments on OMEGA have achieved inferred peak pressures of 56 Gbar (Regan et al 2016 Phys. Rev. Lett. 117 025001). Extensive analysis of the cryogenic target experiments and two- and three-dimensional simulations suggest that power balance, target offset, and target quality are the main limiting factors in target performance. In addition, cross-beam energy transfer (CBET) has been identified as the main mechanism reducing laser coupling. Reaching the goal of demonstrating hydrodynamic equivalence on OMEGA includes improving laser power balance, target position, and target quality at shot time. CBET must also be significantly reduced and several strategies have been identified to address this issue.

Clinical roundtable monograph: unmet needs in the treatment of chronic lymphocytic leukemia: integrating a targeted approach.

Science.gov (United States)

O'Brien, Susan M; Furman, Richard R; Byrd, John C; Smith, Ashbel

2014-01-01

Chronic lymphocytic leukemia (CLL) is the most frequently diagnosed hematologic malignancy in the United States. Although several features can be useful in the diagnosis of CLL, the most important is the immunophenotype.Two staging systems--the Binet system and the Rai classification--are used to assess risk. After diagnosis, the first major therapeutic decision is when to initiate therapy, as a watchful waiting approach is often appropriate for patients with asymptomatic disease. Once a patient has met the criteria for treatment, the choice of therapy is the next major decision. Younger patients (<65 years) often receive more aggressive treatment that typically consists of cytotoxic chemotherapy. There is a great unmet need concerning treatment of older patients with CLL, who often present with more comorbid conditions that can decrease their ability to tolerate particular regimens. The current standard of care for older patients with CLL is rituximab plus chlorambucil. The concept of targeted agents is currently an area of intense interest in CLL. The Bruton’s tyrosine kinase inhibitor ibrutinib is the targeted agent that is furthest along in clinical development. It is associated with an overall survival rate of 83%. Idelalisib targets the phosphatidyl inositol 3-kinase and is under evaluation in pivotal trials. Targeted agents offer much promise in terms of efficacy, toxicity, and oral availability. They will change the management of patients with CLL.

Impact of Clinical Factors on the Achievement of Target Blood Pressure in Hypertensive Patients from Ivanovo Region of Russia: Data of 2015.

Science.gov (United States)

Kiselev, A R; Posnenkova, O M; Belova, O A; Romanchuk, S V; Popova, Y V; Prokhorov, M D; Gridnev, V I

2017-12-01

In Russia, blood pressure (BP) control is below the optimal. The little is known about regional features and barriers to adequate BP control in Russian primary care. To evaluate the impact of clinical factors on achieving the target BP in hypertensive patients in one region of Russia. Retrospective medical data of 2015 on 11,129 patients (31.4% male) with hypertension (Htn) from Ivanovo region of Russia were examined. Achievement of target BP was assessed in all patients. We study association between BP control and clinical factors. 45.9% of studied patients with Htn had controlled BP. The frequency of achieving the target BP in subsets of hypertensive patients was 37.8% in patients with diabetes, 39.5% in patients with coronary artery disease, and 29.9% in patients with chronic heart failure. The main clinical factors associated with achieving the target BP in studied hypertensive patients were the advice on alcohol consumption, advice on smoking cessation, and advice on weight reduction. Therapy with main antihypertensive drugs (in particular, beta-blockers and thiazide diuretics) were also factors of optimal BP control in these patients. Comorbidities (chronic heart failure and cardiovascular diseases requiring the prescription of aspirin and statins) and family history of coronary artery disease were associated with inadequate BP control. A negative effect of some antihypertensive drugs (potassium sparing diuretics, ARBs, ACE-Is, and dihydropyridine CCBs) on BP control that was found out in our study requires further investigation. Other studied factors had no influence on BP control in patients with Htn from Ivanovo region. We identified regional factors of BP control in hypertensive patients from Ivanovo region of Russia. It is shown that individual medical education (in particular, medical advices) is the most important factor of optimal BP control. The intervention with antihypertensive therapy (beta-blockers and thiazide diuretics) facilitates the

Implementing genomics and pharmacogenomics in the clinic: The National Human Genome Research Institute's genomic medicine portfolio.

Science.gov (United States)

Manolio, Teri A

2016-10-01

Increasing knowledge about the influence of genetic variation on human health and growing availability of reliable, cost-effective genetic testing have spurred the implementation of genomic medicine in the clinic. As defined by the National Human Genome Research Institute (NHGRI), genomic medicine uses an individual's genetic information in his or her clinical care, and has begun to be applied effectively in areas such as cancer genomics, pharmacogenomics, and rare and undiagnosed diseases. In 2011 NHGRI published its strategic vision for the future of genomic research, including an ambitious research agenda to facilitate and promote the implementation of genomic medicine. To realize this agenda, NHGRI is consulting and facilitating collaborations with the external research community through a series of "Genomic Medicine Meetings," under the guidance and leadership of the National Advisory Council on Human Genome Research. These meetings have identified and begun to address significant obstacles to implementation, such as lack of evidence of efficacy, limited availability of genomics expertise and testing, lack of standards, and difficulties in integrating genomic results into electronic medical records. The six research and dissemination initiatives comprising NHGRI's genomic research portfolio are designed to speed the evaluation and incorporation, where appropriate, of genomic technologies and findings into routine clinical care. Actual adoption of successful approaches in clinical care will depend upon the willingness, interest, and energy of professional societies, practitioners, patients, and payers to promote their responsible use and share their experiences in doing so. Published by Elsevier Ireland Ltd.

Gross tumor volume and clinical target volume: soft-tissue sarcoma of the extremities

International Nuclear Information System (INIS)

Lartigau, E.; Kantor, G.; Lagarde, P.; Taieb, S.; Ceugnart, L.; Vilain, M.O.; Penel, N.; Depadt, G.

2001-01-01

Soft tissue sarcomas of the extremities are currently treated with more conservative and functional approaches, combining surgery, radiotherapy and chemotherapy. The role of external beam radiotherapy and brachytherapy has been defined through randomized studies performed in the 80's and 90's. However, the ubiquity of tumour location for these tumours makes difficult a systematic definition of local treatments. Tumour volume definition is based on pre and post surgical imaging (MRI) and on described pathological report. The clinical target volume will take into account quality of the resection and anatomical barriers and will be based on an anatomy and not only on safety margins around the tumour bed. General rules for this irradiation (doses, volumes) and principal results will be presented. (authors)

Recent advances in targeted drug therapy for hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

FAN Yongqiang

2018-02-01

Full Text Available More and more clinical trials have proved the efficacy of targeted drugs in the treatment of hepatocellular carcinoma (HCC. With the development of science and technology, more and more targeted drugs have appeared. In recent years, targeted drugs such as regorafenib and ramucirumab have shown great potential in related clinical trials. In addition, there are ongoing clinical trials for second-line candidate drugs, such as c-Met inhibitors tivantinib and cabozantinib and a VEGFR-2 inhibitor ramucirumab. This article summarizes the advances in targeted drug therapy for HCC and related trial data, which provides a reference for further clinical trials and treatment.

A national stakeholder consensus study of challenges and priorities for clinical learning environments in postgraduate medical education

NARCIS (Netherlands)

Kilty, Caroline; Wiese, Anel; Bergin, Colm; Flood, Patrick; Fu, Na; Horgan, Mary; Higgins, Agnes; Maher, Bridget; O’Kane, Grainne; Prihodova, Lucia; Slattery, Dubhfeasa; Stoyanov, Slavi; Bennett, Deirdre

2018-01-01

Background: High quality clinical learning environments (CLE) are critical to postgraduate medical education (PGME). The understaffed and overcrowded environments in which many residents work present a significant challenge to learning. The purpose of this study was to develop a national expert

On the Fielding of a High Gain, Shock-Ignited Target on the National Ignitiion Facility in the Near Term

International Nuclear Information System (INIS)

Perkins, L.J.; Betti, R.; Schurtz, G.P.; Craxton, R.S.; Dunne, A.M.; LaFortune, K.N.; Schmitt, A.J.; McKenty, P.W.; Bailey, D.S.; Lambert, M.A.; Ribeyre, X.; Theobald, W.R.; Strozzi, D.J.; Harding, D.R.; Casner, A.; Atzemi, S.; Erbert, G.V.; Andersen, K.S.; Murakami, M.; Comley, A.J.; Cook, R.C.; Stephens, R.B.

2010-01-01

Shock ignition, a new concept for igniting thermonuclear fuel, offers the possibility for a near-term (∼3-4 years) test of high gain inertial confinement fusion on the National Ignition Facility at less than 1MJ drive energy and without the need for new laser hardware. In shock ignition, compressed fusion fuel is separately ignited by a strong spherically converging shock and, because capsule implosion velocities are significantly lower than those required for conventional hotpot ignition, fusion energy gains of ∼60 may be achievable on NIF at laser drive energies around ∼0.5MJ. Because of the simple all-DT target design, its in-flight robustness, the potential need for only 1D SSD beam smoothing, minimal early time LPI preheat, and use of present (indirect drive) laser hardware, this target may be easier to field on NIF than a conventional (polar) direct drive hotspot ignition target. Like fast ignition, shock ignition has the potential for high fusion yields at low drive energy, but requires only a single laser with less demanding timing and spatial focusing requirements. Of course, conventional symmetry and stability constraints still apply. In this paper we present initial target performance simulations, delineate the critical issues and describe the immediate-term R and D program that must be performed in order to test the potential of a high gain shock ignition target on NIF in the near term.

Review of the Interaction Between Body Composition and Clinical Outcomes in Metastatic Renal Cell Cancer Treated With Targeted Therapies

Directory of Open Access Journals (Sweden)

Steven M Yip

2016-03-01

Full Text Available Treatment of metastatic renal cell cancer (mRCC currently focuses on inhibition of the vascular endothelial growth factor pathway and the mammalian target of rapamycin (mTOR pathway. Obesity confers a higher risk of RCC. However, the influence of obesity on clinical outcomes in mRCC in the era of targeted therapy is less clear. This review focuses on the impact of body composition on targeted therapy outcomes in mRCC. The International Metastatic Renal Cell Carcinoma Database Consortium database has the largest series of patients evaluating the impact of body mass index (BMI on outcomes in mRCC patients treated with targeted therapy. Overall survival was significantly improved in overweight patients (BMI ≥ 25 kg/m2, and this observation was externally validated in patients who participated in Pfizer trials. In contrast, sarcopenia is consistently associated with increased toxicity to inhibitors of angiogenesis and mTOR. Strengthening patients with mRCC and sarcopenia, through a structured exercise program and dietary intervention, may improve outcomes in mRCC treated with targeted therapies. At the same time, the paradox of obesity being a risk factor for RCC while offering a better overall survival in response to targeted therapy needs to be further evaluated.

Targeting death receptors to fight cancer: from biological rational to clinical implementation.

Science.gov (United States)

Mocellin, S

2010-01-01

Considering that most currently available chemotherapeutic drugs work by inducing cell apoptosis, it is not surprising that many expectations in cancer research come from the therapeutic exploitation of the naturally occurring death pathways. Receptor mediated apoptosis depends upon the engagement of specific ligands with their respective membrane receptors and - within the frame of complex regulatory networks - modulates some key physiological and pathological processes such as lymphocyte survival, inflammation and infectious diseases. A pivotal observation was that some of these pathways may be over activated in cancer under particular circumstances, which opened the avenue for tumor-specific therapeutic interventions. Although one death-related ligand (e.g., tumor necrosis factor, TNF) is currently the basis of effective anticancer regimens in the clinical setting, the systemic toxicity is hampering its wide therapeutic exploitation. However, strategies to split the therapeutic from the toxic TNF activity are being devised. Furthermore, other death receptor pathways (e.g., Fas/FasL, TRAIL/TRAIL receptor) are being intensively investigated in order to therapeutically exploit their activity against cancer. This article summarizes the current knowledge on the molecular features of death receptor pathways that make them an attractive target for anticancer therapeutics. In addition, the results so far obtained in the clinical oncology setting as well as the issues to be faced while interfering with these pathways for therapeutic purposes will be overviewed.

Current progress in NIF target concepts

International Nuclear Information System (INIS)

Gobby, P.L.; Foreman, L.R.; Thoma, D.J.; Jacobson, L.A.; Hollis, R.V.; Barrera, J.; Mitchell, M.A.; Salazar, M.A.; Salzer, L.J.

1996-01-01

Target concepts for the National Ignition Facility (NIF) require progress in the art and science of target fabrication. Three distinct issues are addressed: beryllium fuel capsules, foam-buffered direct drive, and high-density gas-filled hohlraums. In all cases experiments on the existing Nova laser at LLNL are either in progress or planned for the near future to test the various concepts. Consequently, target fabrication must be able to deliver targets appropriate for each

Recurrence pattern of squamous cell carcinoma in the midthoracic esophagus: implications for the clinical target volume design of postoperative radiotherapy

Directory of Open Access Journals (Sweden)

Wang X

2016-10-01

stations 2, 4, 5, and 7 LNs should be delineated as clinical target volume of postoperative prophylactic irradiation, and upper abdominal LNs should be excluded. While for midthoracic ESCC with three or more positive nodes, upper abdominal LNs should also be included. The length of tumor and histological differentiation should be considered comprehensively to design the clinical target volume for radiotherapy. Keywords: esophagus cancer, radiotherapy, recurrence and metastasis, clinical target volume

Recent advances in indirect drive ICF target physics at LLNL

International Nuclear Information System (INIS)

Hammel, B.A.; Bernat, T.P.; Collins, G.W.; Haan, S.; Landen, O.L.; MacGowan, B.J.; Suter, L.J.

1999-01-01

In preparation for ignition on the National Ignition Facility, the Lawrence Livermore National Laboratory's Inertial Confinement Fusion Program, working in collaboration with Los Alamos National Laboratory, Commissariat a l'Energie Atomique (CEA), and Laboratory for Laser Energetics at the University of Rochester, has performed a broad range of experiments on the Nova and Omega lasers to test the fundamentals of the NIF target designs. These studies have refined our understanding of the important target physics, and have led to many of the specifications for the NIF laser and the cryogenic ignition targets. Our recent work has been focused in the areas of hohlraum energetics, symmetry, shock physics, and target design optimization and fabrication. (author)

Improving End-of-Life Care: Palliative Care Embedded in an Oncology Clinic Specializing in Targeted and Immune-Based Therapies.

Science.gov (United States)

Einstein, David J; DeSanto-Madeya, Susan; Gregas, Matthew; Lynch, Jessica; McDermott, David F; Buss, Mary K

2017-09-01

Patients with advanced cancer benefit from early involvement of palliative care. The ideal method of palliative care integration remains to be determined, as does its effectiveness for patients treated with targeted and immune-based therapies. We studied the impact of an embedded palliative care team that saw patients in an academic oncology clinic specializing in targeted and immune-based therapies. Patients seen on a specific day accessed the embedded model, on the basis of automatic criteria; patients seen other days could be referred to a separate palliative care clinic (usual care). We abstracted data from the medical records of 114 patients who died during the 3 years after this model's implementation. Compared with usual care (n = 88), patients with access to the embedded model (n = 26) encountered palliative care as outpatients more often ( P = .003) and earlier (mean, 231 v 109 days before death; P 7 days before death-a core Quality Oncology Practice Initiative metric-was higher in the embedded model (odds ratio, 5.60; P = .034). Place of death ( P = .505) and end-of-life chemotherapy (odds ratio, 0.361; P = .204) did not differ between the two arms. A model of embedded and automatically triggered palliative care among patients treated exclusively with targeted and immune-based therapies was associated with significant improvements in use and timing of palliative care and hospice, compared with usual practice.

Pre-clinical Safety and Off-Target Studies to Support Translation of AAV-Mediated RNAi Therapy for FSHD.

Science.gov (United States)

Wallace, Lindsay M; Saad, Nizar Y; Pyne, Nettie K; Fowler, Allison M; Eidahl, Jocelyn O; Domire, Jacqueline S; Griffin, Danielle A; Herman, Adam C; Sahenk, Zarife; Rodino-Klapac, Louise R; Harper, Scott Q

2018-03-16

RNAi emerged as a prospective molecular therapy nearly 15 years ago. Since then, two major RNAi platforms have been under development: oligonucleotides and gene therapy. Oligonucleotide-based approaches have seen more advancement, with some promising therapies that may soon reach market. In contrast, vector-based approaches for RNAi therapy have remained largely in the pre-clinical realm, with limited clinical safety and efficacy data to date. We are developing a gene therapy approach to treat the autosomal-dominant disorder facioscapulohumeral muscular dystrophy. Our strategy involves silencing the myotoxic gene DUX4 using adeno-associated viral vectors to deliver targeted microRNA expression cassettes (miDUX4s). We previously demonstrated proof of concept for this approach in mice, and we are now taking additional steps here to assess safety issues related to miDUX4 overexpression and sequence-specific off-target silencing. In this study, we describe improvements in vector design and expansion of our miDUX4 sequence repertoire and report differential toxicity elicited by two miDUX4 sequences, of which one was toxic and the other was not. This study provides important data to help advance our goal of translating RNAi gene therapy for facioscapulohumeral muscular dystrophy.

Use of the target diagnostic control system in the National Ignition Facility

Energy Technology Data Exchange (ETDEWEB)

Shelton, R; Lagin, L; Nelson, J

2011-07-25

The extreme physics of targets shocked by NIF's 192-beam laser are observed by a diverse suite of diagnostics including optical backscatter, time-integrated, time resolved and gated X-ray sensors, laser velocity interferometry, and neutron time of flight. Diagnostics to diagnose fusion ignition implosion and neutron emissions have been developed. A Diagnostic Control System (DCS) for both hardware and software facilitates development and eases integration. Each complex diagnostic typically uses an ensemble of electronic instruments attached to sensors, digitizers, cameras, and other devices. In the DCS architecture each instrument is interfaced to a low-cost Window XP processor and Java application. Instruments are aggregated as needed in the supervisory system to form an integrated diagnostic. The Java framework provides data management, control services and operator GUI generation. During the past several years, over thirty-six diagnostics have been deployed using this architecture in support of the National Ignition Campaign (NIC). The DCS architecture facilitates the expected additions and upgrades to diagnostics as more experiments are performed. This paper presents the DCS architecture, framework and our experiences in using it during the NIC to operate, upgrade and maintain a large set of diagnostic instruments.

Use of the target diagnostic control system in the National Ignition Facility

International Nuclear Information System (INIS)

Shelton, R.; Lagin, L.; Nelson, J.

2011-01-01

The extreme physics of targets shocked by NIF's 192-beam laser are observed by a diverse suite of diagnostics including optical backscatter, time-integrated, time resolved and gated X-ray sensors, laser velocity interferometry, and neutron time of flight. Diagnostics to diagnose fusion ignition implosion and neutron emissions have been developed. A Diagnostic Control System (DCS) for both hardware and software facilitates development and eases integration. Each complex diagnostic typically uses an ensemble of electronic instruments attached to sensors, digitizers, cameras, and other devices. In the DCS architecture each instrument is interfaced to a low-cost Window XP processor and Java application. Instruments are aggregated as needed in the supervisory system to form an integrated diagnostic. The Java framework provides data management, control services and operator GUI generation. During the past several years, over thirty-six diagnostics have been deployed using this architecture in support of the National Ignition Campaign (NIC). The DCS architecture facilitates the expected additions and upgrades to diagnostics as more experiments are performed. This paper presents the DCS architecture, framework and our experiences in using it during the NIC to operate, upgrade and maintain a large set of diagnostic instruments.

Feasibility of using ultra-high field (7 T MRI for clinical surgical targeting.

Directory of Open Access Journals (Sweden)

Yuval Duchin

Full Text Available The advantages of ultra-high magnetic field (7 Tesla MRI for basic science research and neuroscience applications have proven invaluable. Structural and functional MR images of the human brain acquired at 7 T exhibit rich information content with potential utility for clinical applications. However, (1 substantial increases in susceptibility artifacts, and (2 geometrical distortions at 7 T would be detrimental for stereotactic surgeries such as deep brain stimulation (DBS, which typically use 1.5 T images for surgical planning. Here, we explore whether these issues can be addressed, making feasible the use of 7 T MRI to guide surgical planning. Twelve patients with Parkinson's disease, candidates for DBS, were scanned on a standard clinical 1.5 T MRI and a 7 T MRI scanner. Qualitative and quantitative assessments of global and regional distortion were evaluated based on anatomical landmarks and transformation matrix values. Our analyses show that distances between identical landmarks on 1.5 T vs. 7 T, in the mid-brain region, were less than one voxel, indicating a successful co-registration between the 1.5 T and 7 T images under these specific imaging parameter sets. On regional analysis, the central part of the brain showed minimal distortion, while inferior and frontal areas exhibited larger distortion due to proximity to air-filled cavities. We conclude that 7 T MR images of the central brain regions have comparable distortions to that observed on a 1.5 T MRI, and that clinical applications targeting structures such as the STN, are feasible with information-rich 7 T imaging.

Olfactory Function and Associated Clinical Correlates in Former National Football League Players.

Science.gov (United States)

Alosco, Michael L; Jarnagin, Johnny; Tripodis, Yorghos; Platt, Michael; Martin, Brett; Chaisson, Christine E; Baugh, Christine M; Fritts, Nathan G; Cantu, Robert C; Stern, Robert A

2017-02-15

Professional American football players incur thousands of repetitive head impacts (RHIs) throughout their lifetime. The long-term consequences of RHI are not well characterized, but may include olfactory dysfunction. RHI has been associated with changes to brain regions involved in olfaction, and olfactory impairment is common after traumatic brain injury. Olfactory dysfunction is a frequent early sequelae of neurodegenerative diseases (e.g., Alzheimer's disease), and RHI is associated with the neurodegenerative disease, chronic traumatic encephalopathy (CTE). We examined olfaction, and its association with clinical measures, in former National Football League (NFL) players. Ninety-five former NFL players (ages 40-69) and 28 same-age controls completed a neuropsychological and neuropsychiatric evaluation as part of a National Institutes of Health-funded study. The Brief Smell Identification Test (B-SIT) assessed olfaction. Principal component analysis generated a four-factor structure of the clinical measures: behavioral/mood, psychomotor speed/executive function, and verbal and visual memory. Former NFL players had worse B-SIT scores relative to controls (p = 0.0096). A B-SIT cutoff of 11 had the greatest accuracy (c-statistic = 0.61) and specificity (79%) for discriminating former NFL players from controls. In the former NFL players, lower B-SIT scores correlated with greater behavioral/mood impairment (p = 0.0254) and worse psychomotor speed/executive functioning (p = 0.0464) after controlling for age and education. Former NFL players exhibited lower olfactory test scores relative to controls, and poorer olfactory test performance was associated with worse neuropsychological and neuropsychiatric functioning. Future work that uses more-comprehensive tests of olfaction and structural and functioning neuroimaging may improve understanding on the association between RHI and olfaction.

Which Clinical and Patient Factors Influence the National Economic Burden of Hospital Readmissions After Total Joint Arthroplasty?

Science.gov (United States)

Kurtz, Steven M; Lau, Edmund C; Ong, Kevin L; Adler, Edward M; Kolisek, Frank R; Manley, Michael T

2017-12-01

The Affordable Care Act of 2010 advanced the economic model of bundled payments for total joint arthroplasty (TJA), in which hospitals will be financially responsible for readmissions, typically at 90 days after surgery. However, little is known about the financial burden of readmissions and what patient, clinical, and hospital factors drive readmission costs. (1) What is the incidence, payer mix, and demographics of THA and TKA readmissions in the United States? (2) What patient, clinical, and hospital factors are associated with the cost of 30- and 90-day readmissions after primary THA and TKA? (3) Are there any differences in the economic burden of THA and TKA readmissions between payers? (4) What types of THA and TKA readmissions are most costly to the US hospital system? The recently developed Nationwide Readmissions Database from the Healthcare Cost and Utilization Project (2006 hospitals from 21 states) was used to identify 719,394 primary TJAs and 62,493 90-day readmissions in the first 9 months of 2013 based on International Classification of Diseases, 9th Revision, Clinical Modification codes. We classified the reasons for readmissions as either procedure- or medical-related. Cost-to-charge ratios supplied with the Nationwide Readmissions Database were used to compute the individual per-patient cost of 90-day readmissions as a continuous variable in separate general linear models for THA and TKA. Payer, patient, clinical, and hospital factors were treated as covariates. We estimated the national burden of readmissions by payer and by the reason for readmission. The national rates of 30- and 90-day readmissions after THA were 4% (95% confidence interval [CI], 4.2%-4.5%) and 8% (95% CI, 7.5%-8.1%), respectively. The national rates of 30- and 90-day readmissions after primary TKA were 4% (95% CI, 3.8%-4.0%) and 7% (95% CI, 6.8%-7.2%), respectively. The five most important variables responsible for the cost of 90-day THA readmissions (in rank order, based

Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies

Science.gov (United States)

2016-10-01

Physics of Cancer Metabolism This application seeks to put together a multidiscipline team of experts in various institutions in USA to assemble and...of this project is to build a research cohort of engaged volunteers that reflects the racial , ethnic, and socioeconomic diversity of New York City...assessed in a randomized, phase III clinical trial. Conflict of interest: Advisory Board: Joe O’Sullivan holds consulting/ advisory roles with Bayer

Targeting the interleukin-11 receptor α in metastatic prostate cancer: A first-in-man study.

Science.gov (United States)

Pasqualini, Renata; Millikan, Randall E; Christianson, Dawn R; Cardó-Vila, Marina; Driessen, Wouter H P; Giordano, Ricardo J; Hajitou, Amin; Hoang, Anh G; Wen, Sijin; Barnhart, Kirstin F; Baze, Wallace B; Marcott, Valerie D; Hawke, David H; Do, Kim-Anh; Navone, Nora M; Efstathiou, Eleni; Troncoso, Patricia; Lobb, Roy R; Logothetis, Christopher J; Arap, Wadih

2015-07-15

Receptors in tumor blood vessels are attractive targets for ligand-directed drug discovery and development. The authors have worked systematically to map human endothelial receptors ("vascular zip codes") within tumors through direct peptide library selection in cancer patients. Previously, they selected a ligand-binding motif to the interleukin-11 receptor alpha (IL-11Rα) in the human vasculature. The authors generated a ligand-directed, peptidomimetic drug (bone metastasis-targeting peptidomimetic-11 [BMTP-11]) for IL-11Rα-based human tumor vascular targeting. Preclinical studies (efficacy/toxicity) included evaluating BMTP-11 in prostate cancer xenograft models, drug localization, targeted apoptotic effects, pharmacokinetic/pharmacodynamic analyses, and dose-range determination, including formal (good laboratory practice) toxicity across rodent and nonhuman primate species. The initial BMTP-11 clinical development also is reported based on a single-institution, open-label, first-in-class, first-in-man trial (National Clinical Trials number NCT00872157) in patients with metastatic, castrate-resistant prostate cancer. BMTP-11 was preclinically promising and, thus, was chosen for clinical development in patients. Limited numbers of patients who had castrate-resistant prostate cancer with osteoblastic bone metastases were enrolled into a phase 0 trial with biology-driven endpoints. The authors demonstrated biopsy-verified localization of BMTP-11 to tumors in the bone marrow and drug-induced apoptosis in all patients. Moreover, the maximum tolerated dose was identified on a weekly schedule (20-30 mg/m(2) ). Finally, a renal dose-limiting toxicity was determined, namely, dose-dependent, reversible nephrotoxicity with proteinuria and casts involving increased serum creatinine. These biologic endpoints establish BMTP-11 as a targeted drug candidate in metastatic, castrate-resistant prostate cancer. Within a larger discovery context, the current findings indicate that

2010 national progress report on R and D on LEU fuel and target technology in Argentina

International Nuclear Information System (INIS)

Balart, S.; Blaumann, H.; Cristini, P.; Gonzalez, A.G.; Gonzalez, R.; Hermida, J.D.; Lopez, M.; Mirandou, M.; Taboada, H.

2010-01-01

Since last RRFM meeting, CNEA has deployed several related tasks. The RA-6 MTR type reactor, converted its core from HEU to a new LEU silicide one is scaling up the power, according to a protocol requested by the national regulatory body, ARN. CNEA is deploying an intense R and D activity to fabricate both dispersed U-Mo (Al-Si matrix and Al cladding) and monolithic (Zry-4 cladding) miniplates to develop possible solutions to VHD dispersed and monolithic fuels technical problems. Some monolithic 58% enrichment U8%Mo and U10%Mo are being delivered to INL-DoE to be irradiated in ATR reactor core. A conscientious study on compound interphase formation in both cases is being carried out. CNEA, a worldwide leader on LEU technology for fission radioisotope production is providing Brazil with these radiopharmaceutical products and Egypt and Australia with the technology through INVAP SE. CNEA is also committed to improve the diffusion of LEU target and radiochemical technology for radioisotope production and target and process optimization. Future plans include: 1) Fabrication of a LEU dispersed U-Mo fuel prototype following the recommendations of the IAEA's Good Practices document, to be irradiated in a high flux reactor in the frame of the ARG/4/092 IAEA's Technical Cooperation project. 2) Development of LEU very high density monolithic and dispersed U-Mo fuel plates with Zry-4 or Al cladding as a part of the RERTR program. 3) Optimization of LEU target and radiochemical techniques for radioisotope production. (author)

Target salt 2025: a global overview of national programs to encourage the food industry to reduce salt in foods.

Science.gov (United States)

Webster, Jacqui; Trieu, Kathy; Dunford, Elizabeth; Hawkes, Corinna

2014-08-21

Reducing population salt intake has been identified as a priority intervention to reduce non-communicable diseases. Member States of the World Health Organization have agreed to a global target of a 30% reduction in salt intake by 2025. In countries where most salt consumed is from processed foods, programs to engage the food industry to reduce salt in products are being developed. This paper provides a comprehensive overview of national initiatives to encourage the food industry to reduce salt. A systematic review of the literature was supplemented by key informant questionnaires to inform categorization of the initiatives. Fifty nine food industry salt reduction programs were identified. Thirty eight countries had targets for salt levels in foods and nine countries had introduced legislation for some products. South Africa and Argentina have both introduced legislation limiting salt levels across a broad range of foods. Seventeen countries reported reductions in salt levels in foods-the majority in bread. While these trends represent progress, many countries have yet to initiate work in this area, others are at early stages of implementation and further monitoring is required to assess progress towards achieving the global target.

National Clinical Skills Competition: an effective simulation-based method to improve undergraduate medical education in China.

Science.gov (United States)

Jiang, Guanchao; Chen, Hong; Wang, Qiming; Chi, Baorong; He, Qingnan; Xiao, Haipeng; Zhou, Qinghuan; Liu, Jing; Wang, Shan

2016-01-01

The National Clinical Skills Competition has been held in China for 5 consecutive years since 2010 to promote undergraduate education reform and improve the teaching quality. The effects of the simulation-based competition will be analyzed in this study. Participation in the competitions and the compilation of the questions used in the competition finals are summarized, and the influence and guidance quality are further analyzed. Through the nationwide distribution of questionnaires in medical colleges, the effects of the simulation-based competition on promoting undergraduate medical education reform were evaluated. The results show that approximately 450 students from more than 110 colleges (accounting for 81% of colleges providing undergraduate clinical medical education in China) participated in the competition each year. The knowledge, skills, and attitudes were comprehensively evaluated by simulation-based assessment. Eight hundred and eighty copies of the questionnaires were distributed to 110 participating medical schools in 2015. In total, 752 valid responses were received across 95 schools. The majority of the interviewees agreed or strongly agreed that competition promoted the adoption of advanced educational principles (76.8%), updated the curriculum model and instructional methods (79.8%), strengthened faculty development (84.0%), improved educational resources (82.1%), and benefited all students (53.4%). The National Clinical Skills Competition is widely accepted in China. It has effectively promoted the reform and development of undergraduate medical education in China.

Performance scores in general practice: a comparison between the clinical versus medication-based approach to identify target populations.

Directory of Open Access Journals (Sweden)

Olivier Saint-Lary

Full Text Available CONTEXT: From one country to another, the pay-for-performance mechanisms differ on one significant point: the identification of target populations, that is, populations which serve as a basis for calculating the indicators. The aim of this study was to compare clinical versus medication-based identification of populations of patients with diabetes and hypertension over the age of 50 (for men or 60 (for women, and any consequences this may have on the calculation of P4P indicators. METHODS: A comparative, retrospective, observational study was carried out with clinical and prescription data from a panel of general practitioners (GPs, the Observatory of General Medicine (OMG for the year 2007. Two indicators regarding the prescription for statins and aspirin in these populations were calculated. RESULTS: We analyzed data from 21.690 patients collected by 61 GPs via electronic medical files. Following the clinical-based approach, 2.278 patients were diabetic, 8,271 had hypertension and 1.539 had both against respectively 1.730, 8.511 and 1.304 following the medication-based approach (% agreement = 96%, kappa = 0.69. The main reasons for these differences were: forgetting to code the morbidities in the clinical approach, not taking into account the population of patients who were given life style and diet rules only or taking into account patients for whom morbidities other than hypertension could justify the use of antihypertensive drugs in the medication-based approach. The mean (confidence interval per doctor was 33.7% (31.5-35.9 for statin indicator and 38.4% (35.4-41.4 for aspirin indicator when the target populations were identified on the basis of clinical criteria whereas they were 37.9% (36.3-39.4 and 43.8% (41.4-46.3 on the basis of treatment criteria. CONCLUSION: The two approaches yield very "similar" scores but these scores cover different realities and offer food for thought on the possible usage of these indicators in the

Recent advances in indirect drive ICF target physics

International Nuclear Information System (INIS)

Hammel, B.A.

2002-01-01

The National Ignition Facility (NIF), currently under construction, will be used for the study of ignition physics in inertially confined targets, as well as basic and applied research in the field of high energy density science. In preparing for ignition on the NIF, the Lawrence Livermore National Laboratory's Inertial Confinement Fusion Program, in collaboration with Los Alamos National Laboratory (LANL), Sandia National Laboratory (SNL), the Laboratory for Laser Energetics (LLE), General Atomics (GA), and the Commissariat a l'Energie Atomique (CEA), is working to refine ignition designs, develop improved experimental methods, and fabricate and test cryogenic targets required for ignition. This paper will briefly review NIF construction progress, and summarize advances in these areas. (author)

A content analysis of preconception health education materials: characteristics, strategies, and clinical-behavioral components.

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Levis, Denise M; Westbrook, Kyresa

2013-01-01

Many health organizations and practitioners in the United States promote preconception health (PCH) to consumers. However, summaries and evaluations of PCH promotional activities are limited. We conducted a content analysis of PCH health education materials collected from local-, state-, national-, and federal-level partners by using an existing database of partners, outreach to maternal and child health organizations, and a snowball sampling technique. Not applicable. Not applicable. Thirty-two materials were included for analysis, based on inclusion/exclusion criteria. A codebook guided coding of materials' characteristics (type, authorship, language, cost), use of marketing and behavioral strategies to reach the target population (target audience, message framing, call to action), and inclusion of PCH subject matter (clinical-behavioral components). The self-assessment of PCH behaviors was the most common material (28%) to appear in the sample. Most materials broadly targeted women, and there was a near-equal distribution in targeting by pregnancy planning status segments (planners and nonplanners). "Practicing PCH benefits the baby's health" was the most common message frame used. Materials contained a wide range of clinical-behavioral components. Strategic targeting of subgroups of consumers is an important but overlooked strategy. More research is needed around PCH components, in terms of packaging and increasing motivation, which could guide use and placement of clinical-behavioral components within promotional materials.

Demographic characteristics, social competence, and behavior problems in children with gender identity disorder: a cross-national, cross-clinic comparative analysis.

Science.gov (United States)

Cohen-Kettenis, Peggy T; Owen, Allison; Kaijser, Vanessa G; Bradley, Susan J; Zucker, Kenneth J

2003-02-01

This study examined demographic characteristics, social competence, and behavior problems in clinic-referred children with gender identity problems in Toronto, Canada (N = 358), and Utrecht, The Netherlands (N = 130). The Toronto sample was, on average, about a year younger than the Utrecht sample at referral, had a higher percentage of boys, had a higher mean IQ, and was less likely to be living with both parents. On the Child Behavior Checklist (CBCL), both groups showed, on average, clinical range scores in both social competence and behavior problems. A CBCL-derived measure of poor peer relations showed that boys in both clinics had worse ratings than did the girls. A multiple regression analysis showed that poor peer relations were the strongest predictor of behavior problems in both samples. This study-the first cross-national, cross-clinic comparative analysis of children with gender identity disorder-found far more similarities than differences in both social competence and behavior problems. The most salient demographic difference was age at referral. Cross-national differences in factors that might influence referral patterns are discussed.

Offensive Counterterrorism Targeted killing in eliminating terrorist target: the case of the USA and Israel

Directory of Open Access Journals (Sweden)

Hermínio Matos

2012-01-01

Full Text Available Due to the "global terrorism project", some States have adopted offensive counterterrorism measures which, though within national strategies on security and defense, contemplate the use of military power and the use of lethal force against non-state actors - individuals, groups or terrorist organizations - beyond their national borders. Reformulating the security paradigm has led, in these cases, to policies against terrorism. This is the case of targeted killing - the killing of selected targets - by the USA and Israel. Targeted killing actions - using essentially but not only drones - in Pakistan and Yemen by the American administration, a well as the Israeli response to Palestinian terrorism, are under heated debate in terms of their efficiency and legality. Thus, this paper aims to not only provide an analytical framework on this theme but also analyze the scope and impact of these counter terrorist strategies by the two countries.

Quality of care at ART clinic in Shashamanne referral hospital, West Arsi zone, Oromina National Regional State, South Ethiopia

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Melese Belayneh

2017-01-01

Full Text Available Background Low income nations like Ethiopia, which are heavily affected by HIV pandemic, health system needs to provide comprehensive services for escalating numbers of HIV positive patients. While demand is increasing, resources are not expanding at desirable rates to meet these demands. This leads to the risk of running poor quality antiretroviral therapy in resource limited health facilities. However, there is paucity of research based evidences on the quality of health services in the country in general, and on anti retroviral therapy in particular. Objective To assess quality of care at antiretroviral therapy clinic in Shashamanne Referral Hospital. Method A cross‐sectional study was conducted in Shashamanne Referral hospital from May 30 to June 30,2017.The study population were selected people living with HIV, antiretroviral therapy clinics and health care workers in antiretroviral therapy clinics during the study period. Stratified sampling method was used to identify study population. Interviewer administered questionnaire was employed among 204 patients to assess their satisfaction. Medical records review check list was used to get vital information from documents of 354 patients. Interview guide was also used to assess providers’ view on services. Data were entered by using SPSS version 20 and analyzed using descriptive, bivariate and multivariate techniques. Ethical clearance was obtained from Jimma University College of Public Health and Medical Sciences. Results Resources required for implementation of antiretroviral therapy wee available as per recommendation by the national Guideline. However, scarcity of some OIs and ARV drugs and absence of a few laboratory services seen in the hospital. HIV/AIDS care given in line with national guidelines but study revealed that only 42.7% of clients eligible for isoniazid preventive therapy actually taken it. Average mean satisfaction score of patients was 2.51 and significant

MRO CRISM TARGETED EMPIRICAL RECORD V1.0

Data.gov (United States)

National Aeronautics and Space Administration — This volume contains the CRISM Targeted Empirical Record (TER) archive, a collection of multiband image cubes derived from targeted (gimbaled) observations of Mars'...

Psychosocial impact of participation in the National Veterans Wheelchair Games and Winter Sports Clinic.

Science.gov (United States)

Sporner, Michelle L; Fitzgerald, Shirley G; Dicianno, Brad E; Collins, Diane; Teodorski, Emily; Pasquina, Paul F; Cooper, Rory A

2009-01-01

The purpose of this study was to determine the characteristics of individuals who participate in the National Veterans Wheelchair Games (NVWG) and the Winter Sports Clinic (WSC) for veterans with disabilities. In addition, it was of interest to determine how these events had impacted their lives. Participants were recruited at the 20th Winter Sports Clinic, held in Snowmass Colorado and the 26th National Veterans Wheelchair Games held in Anchorage, Alaska. Data of interest included demographic, sport participation information, community integration, self-esteem, and quality of life. A secondary data analysis was completed to determine how comparable individuals who attended the NVWG/WSC were to individuals who did not participate in these events. The 132 participants were a mean age of 47.4 + 13.4 and lived with a disability for an average of 13.4 + 12.1. Participants felt that the NVWG/WSC increased their knowledge of sports equipment (92%), learning sports (89%), mobility skills (84%), and acceptance of disability (84%). The majority of participants stated that the NVWG/WSC improved their life. Of those who participated at the NVWG/WSC, they tended to be more mobile, but have increased physical and cognitive limitations as measured by the CHART when compared to the non-attendees. Recommending veterans participate in events such as the NVWG and WSC can provide psychosocial benefits to veterans with disabilities.

Implementing genomics and pharmacogenomics in the clinic: The National Human Genome Research Institute’s genomic medicine portfolio

Science.gov (United States)

Manolio, Teri A.

2016-01-01

Increasing knowledge about the influence of genetic variation on human health and growing availability of reliable, cost-effective genetic testing have spurred the implementation of genomic medicine in the clinic. As defined by the National Human Genome Research Institute (NHGRI), genomic medicine uses an individual’s genetic information in his or her clinical care, and has begun to be applied effectively in areas such as cancer genomics, pharmacogenomics, and rare and undiagnosed diseases. In 2011 NHGRI published its strategic vision for the future of genomic research, including an ambitious research agenda to facilitate and promote the implementation of genomic medicine. To realize this agenda, NHGRI is consulting and facilitating collaborations with the external research community through a series of “Genomic Medicine Meetings,” under the guidance and leadership of the National Advisory Council on Human Genome Research. These meetings have identified and begun to address significant obstacles to implementation, such as lack of evidence of efficacy, limited availability of genomics expertise and testing, lack of standards, and diffficulties in integrating genomic results into electronic medical records. The six research and dissemination initiatives comprising NHGRI’s genomic research portfolio are designed to speed the evaluation and incorporation, where appropriate, of genomic technologies and findings into routine clinical care. Actual adoption of successful approaches in clinical care will depend upon the willingness, interest, and energy of professional societies, practitioners, patients, and payers to promote their responsible use and share their experiences in doing so. PMID:27612677

Priority target conditions for algorithms for monitoring children's growth: Interdisciplinary consensus.

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Pauline Scherdel

Full Text Available Growth monitoring of apparently healthy children aims at early detection of serious conditions through the use of both clinical expertise and algorithms that define abnormal growth. Optimization of growth monitoring requires standardization of the definition of abnormal growth, and the selection of the priority target conditions is a prerequisite of such standardization.To obtain a consensus about the priority target conditions for algorithms monitoring children's growth.We applied a formal consensus method with a modified version of the RAND/UCLA method, based on three phases (preparatory, literature review, and rating, with the participation of expert advisory groups from the relevant professional medical societies (ranging from primary care providers to hospital subspecialists as well as parent associations. We asked experts in the pilot (n = 11, reading (n = 8 and rating (n = 60 groups to complete the list of diagnostic classification of the European Society for Paediatric Endocrinology and then to select the conditions meeting the four predefined criteria of an ideal type of priority target condition.Strong agreement was obtained for the 8 conditions selected by the experts among the 133 possible: celiac disease, Crohn disease, craniopharyngioma, juvenile nephronophthisis, Turner syndrome, growth hormone deficiency with pituitary stalk interruption syndrome, infantile cystinosis, and hypothalamic-optochiasmatic astrocytoma (in decreasing order of agreement.This national consensus can be used to evaluate the algorithms currently suggested for growth monitoring. The method used for this national consensus could be re-used to obtain an international consensus.

Double-shell target fabrication workshop-2016 report

Energy Technology Data Exchange (ETDEWEB)

Wang, Y. Morris [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Oertel, John [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Farrell, Michael [General Atomics, San Diego, CA (United States); Baumann, Ted [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Huang, Haibo [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Nikroo, Abbas [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2017-01-10

On June 30, 2016, over 40 representatives from Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), General Atomics (GA), Laboratory for Laser Energetics (LLE), Schafer Corporation, and NNSA headquarter attended a double-shell (DS) target fabrication workshop at Livermore, California. Pushered-single-shell (PSS) and DS metalgas platforms potentially have a large impact on programmatic applications. The goal of this focused workshop is to bring together target fabrication scientists, physicists, and designers to brainstorm future PSS and DS target fabrication needs and strategies. This one-day workshop intends to give an overall view of historical information, recent approaches, and future research activities at each participating organization. Five topical areas have been discussed that are vital to the success of future DS target fabrications, including inner metal shells, foam spheres, outer ablators, fill tube assembly, and metrology.

Enrollment Trends and Disparity Among Patients With Lung Cancer in National Clinical Trials, 1990 to 2012

Science.gov (United States)

Pang, Herbert H.; Stinchcombe, Thomas E.; Wong, Melisa L.; Cheng, Perry; Ganti, Apar Kishor; Sargent, Daniel J.; Zhang, Ying; Hu, Chen; Mandrekar, Sumithra J.; Redman, Mary W.; Manola, Judith B.; Schilsky, Richard L.; Cohen, Harvey J.; Bradley, Jeffrey D.; Adjei, Alex A.; Gandara, David; Ramalingam, Suresh S.; Vokes, Everett E.

2016-01-01

Purpose Under-representation of elderly, women, and racial/ethnic minority patients with cancer in clinical trials is of national concern. The goal of this study was to characterize enrollment trends and disparities by age, sex, and race/ethnicity in lung cancer trials. Methods We analyzed data for 23,006 National Cancer Institute cooperative group lung cancer trial participants and 578,476 patients with lung cancer from the SEER registry from 1990 to 2012. The enrollment disparity difference (EDD) and enrollment disparity ratio (EDR) were calculated on the basis of the proportion of each subgroup in the trial population and the US lung cancer population. Annual percentage changes (APCs) in the subgroup proportions in each population were compared over time. Results Enrollment disparity for patients ≥ 70 years of age with non–small-cell lung cancer improved from 1990 to 2012 (test of parallelism, P = .020), with a remaining EDD of 0.22 (95% CI, 0.19 to 0.25) and EDR of 1.65 (95% CI, 1.51 to 1.82) in 2010 to 2012. No improvement was seen for elderly patients with small-cell lung cancer (SCLC), with an APC of 0.20 (P = .714) among trial participants, despite a rising proportion of elderly patients with SCLC in the US population (APC, 0.32; P = .020). Enrollment disparity for women with lung cancer improved overall, with the gap closing by 2012 (EDD, 0.03 [95% CI, 0.00 to 0.06]; EDR, 1.07 [95% CI, 1.00 to 1.16]). Enrollment disparities persisted without significant improvement for elderly women, blacks, Asians/Pacific Islanders, and Hispanics. Conclusion Under-representation in lung cancer trials improved significantly from 1990 to 2012 for elderly patients with non–small-cell lung cancer and for women, but ongoing efforts to improve the enrollment of elderly patients with SCLC and minorities are needed. Our study highlights the importance of addressing enrollment disparities by demographic and disease subgroups to better target under-represented groups of

Pneumococcal vaccine targeting strategy for older adults: customized risk profiling.

Science.gov (United States)

Balicer, Ran D; Cohen, Chandra J; Leibowitz, Morton; Feldman, Becca S; Brufman, Ilan; Roberts, Craig; Hoshen, Moshe

2014-02-12

Current pneumococcal vaccine campaigns take a broad, primarily age-based approach to immunization targeting, overlooking many clinical and administrative considerations necessary in disease prevention and resource planning for specific patient populations. We aim to demonstrate the utility of a population-specific predictive model for hospital-treated pneumonia to direct effective vaccine targeting. Data was extracted for 1,053,435 members of an Israeli HMO, age 50 and older, during the study period 2008-2010. We developed and validated a logistic regression model to predict hospital-treated pneumonia using training and test samples, including a set of standard and population-specific risk factors. The model's predictive value was tested for prospectively identifying cases of pneumonia and invasive pneumococcal disease (IPD), and was compared to the existing international paradigm for patient immunization targeting. In a multivariate regression, age, co-morbidity burden and previous pneumonia events were most strongly positively associated with hospital-treated pneumonia. The model predicting hospital-treated pneumonia yielded a c-statistic of 0.80. Utilizing the predictive model, the top 17% highest-risk within the study validation population were targeted to detect 54% of those members who were subsequently treated for hospitalized pneumonia in the follow up period. The high-risk population identified through this model included 46% of the follow-up year's IPD cases, and 27% of community-treated pneumonia cases. These outcomes were compared with international guidelines for risk for pneumococcal diseases that accurately identified only 35% of hospitalized pneumonia, 41% of IPD cases and 21% of community-treated pneumonia. We demonstrate that a customized model for vaccine targeting performs better than international guidelines, and therefore, risk modeling may allow for more precise vaccine targeting and resource allocation than current national and international

Clinical characteristics and outcomes of myxedema coma: Analysis of a national inpatient database in Japan

OpenAIRE

Ono, Yosuke; Ono, Sachiko; Yasunaga, Hideo; Matsui, Hiroki; Fushimi, Kiyohide; Tanaka, Yuji

2017-01-01

Background: Myxedema coma is a life-threatening and emergency presentation of hypothyroidism. However, the clinical features and outcomes of this condition have been poorly defined because of its rarity. Methods: We conducted a retrospective observational study of patients diagnosed with myxedema coma from July 2010 through March 2013 using a national inpatient database in Japan. We investigated characteristics, comorbidities, treatments, and in-hospital mortality of patients with myxedem...

[Basic and clinical studies of the gene product-targeting therapy based on leukemogenesis--editorial].

Science.gov (United States)

Chen, Sai-Juan; Chen, Li-Juan; Zhou, Guang-Biao

2005-02-01

In the last twenty years, using all-trans retinoic acid (ATRA) as a differentiation inducer, Shanghai Institute of Hematology has achieved an important breakthrough in the treatment of acute promyelocytic leukemia (APL), which realized the theory of reversing phenotype of cells and provided a successful model of differentiation therapy in cancers. Our group first discovered in the world the variant chromosome translocation t(11;17)(q23;q21) of APL, and cloned the PML-RAR alpha, PLZF-RAR alpha and NPM-RAR alpha fusion genes corresponding to the characterized chromosome translocations t(15;17); t(11;17) and t(5;17) in APL. Moreover, establishment of transgenic mice model of APL proved their effects on leukemogenesis. The ability of ATRA to modify the recruitment of nuclear receptor co-repressor with PML-RAR alpha but not PLZF-RAR alpha caused by the variant chromosome translocation elucidated the therapeutic mechanism of ATRA from the molecular level and provides new insight into transcription-modulating therapy. Since 1994, our group has successfully applied arsenic trioxide (As(2)O(3)) in treating relapsed APL patients, with the complete remission rate of 70% - 80%. The molecular mechanism study revealed that As(2)O(3) exerts a dose-dependent dual effect on APL. Low-dose As(2)O(3) induced partial differentiation of APL cells, while the higher dose induced apoptosis. As(2)O(3) binds ubiquitin like SUMO-1 through the lysine 160 of PML, resulting in the degradation of PML-RAR alpha. Taken together, ATRA and As(2)O(3) target the transcription factor PML-RAR alpha, the former by retinoic acid receptor and the latter by PML sumolization, both induce PML-RAR alpha degradation and APL cells differentiation and apoptosis. Because of the different acting pathways, ATRA and As(2)O(3) have no cross-resistance and can be used as combination therapy. Clinical trial in newly diagnosed APL patients showed that ATRA/As(2)O(3) in combination yields a longer disease-free survival

National Practice Patterns for Clinical T1N0 Nasopharyngeal Cancer in the Elderly: A National Cancer Data Base Analysis.

Science.gov (United States)

Post, Carl M; Lin, Chi; Adeberg, Sebastian; Gupta, Mrigank; Zhen, Weining; Verma, Vivek

2018-03-01

The standard of care for T1N0 nasopharyngeal cancer (NPC) is definitive radiation therapy (RT). However, practice patterns in the elderly may not necessarily follow national guidelines. Herein, we investigated national practice patterns for T1N0 NPC. The National Cancer Data Base (NCDB) was queried for clinical T1N0 primary NPC cases (2004-2013) in patients ≥70 years old. Patient, tumor, and treatment parameters were extracted. Kaplan-Meier analysis was used to compare overall survival (OS) between patients receiving RT versus those under observation. Logistic regression was used to examine variables associated with receipt of RT. Cox proportional hazards modeling determined variables associated with OS. Landmark analysis of patients surviving 1 year or more was performed to assess survival differences between groups. In total, data of 147 patients were analyzed. RT was delivered to 89 patients (61%), whereas 58 (39%) patients underwent observation. On multivariable analysis, older patients were less likely to receive RT (p=0.003), but there were no differences between groups in terms of Charlson-Deyo comorbidity index. Median and 5-year OS in patients receiving RT versus those under observation were 71 and 33 months, and 59% and 48% (p=0.011), respectively. For patients surviving 1 year or more (n=96), there was a strong trend showing that receipt of RT was associated with better median and 5-year OS. This National Data Base analysis shows that observation is relatively common for T1N0 NPC in the elderly, but is associated with poorer survival. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

SU-E-P-03: The Australian Clinical Dosimetry Service, a Bespoke National Solution

International Nuclear Information System (INIS)

Williams, I; Lye, J; Alves, A; Lehmann, J; Kenny, J; Dunn, L; Kron, T

2015-01-01

Purpose: The Australian Clinical Dosimetry Service, (ACDS) was a pilot program to enable the Australian Government to determine whether a locally designed audit program was suitable for mitigating dosimetric error risk to radiotherapy patients within Australia. The outcomes from four years of operations will be presented and discussed with a focus why and how the pilot requirements were met. The consequnces of success will be considered, the lessons learnt from the pilot program and how they are impacting the future ACDS design, operation and engagement with stakeholders. Methods: The ACDS was designed over 2010/11 by experts drawn from the three professions in consultation with the national Department of Health. The list of outcomes required over a three year pilot was expressed in a Memorandum of Understanding, (MoU) between Health and the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) which hosted the ACDS. Results: The ACDS has achieved all the MoU requirements. This paper describes how the staff within the ACDS engaged with the professional clinical workforce and provided a successful and functioning audit service. It identifies the strengths and weaknesses within the MoU and the ACDS structure and how the ACDS resolved a number of conflicting issues. It identifies the successes within the ACDS and how these were achieved. It provides details to assist and advise those seeking to design or modify national or regional auditing programs. Finally the paper reviews potential futures for the ACDS. Conclusion: The raw number of audits and outcomes indicate that the ACDS has met the MoU auditing requirements. The reasons for the ACDS’ success are highly dependent on: attracting quality staff who can respond with agility to changing situations, a high level of communication with the professional community, a high level of engagement by the community and an interested and engaged Federal Department. The Australian Clinical Dosimetry Service is a

SU-E-P-03: The Australian Clinical Dosimetry Service, a Bespoke National Solution

Energy Technology Data Exchange (ETDEWEB)

Williams, I; Lye, J; Alves, A [Australian Clinical Dosimetry Service, Yallambie, Vic (Australia); Lehmann, J [University of Sydney, Sydney (Australia); Kenny, J [Epworth HealthCare, Richmond, VIC (Australia); Dunn, L [Royal Melbourne Institute of Technology, Melbourne (Australia); Kron, T [Peter MacCallum Cancer Instit., Melbourne (Australia)

2015-06-15

Purpose: The Australian Clinical Dosimetry Service, (ACDS) was a pilot program to enable the Australian Government to determine whether a locally designed audit program was suitable for mitigating dosimetric error risk to radiotherapy patients within Australia. The outcomes from four years of operations will be presented and discussed with a focus why and how the pilot requirements were met. The consequnces of success will be considered, the lessons learnt from the pilot program and how they are impacting the future ACDS design, operation and engagement with stakeholders. Methods: The ACDS was designed over 2010/11 by experts drawn from the three professions in consultation with the national Department of Health. The list of outcomes required over a three year pilot was expressed in a Memorandum of Understanding, (MoU) between Health and the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) which hosted the ACDS. Results: The ACDS has achieved all the MoU requirements. This paper describes how the staff within the ACDS engaged with the professional clinical workforce and provided a successful and functioning audit service. It identifies the strengths and weaknesses within the MoU and the ACDS structure and how the ACDS resolved a number of conflicting issues. It identifies the successes within the ACDS and how these were achieved. It provides details to assist and advise those seeking to design or modify national or regional auditing programs. Finally the paper reviews potential futures for the ACDS. Conclusion: The raw number of audits and outcomes indicate that the ACDS has met the MoU auditing requirements. The reasons for the ACDS’ success are highly dependent on: attracting quality staff who can respond with agility to changing situations, a high level of communication with the professional community, a high level of engagement by the community and an interested and engaged Federal Department. The Australian Clinical Dosimetry Service is a

Ambulatory-based education in internal medicine: current organization and implications for transformation. Results of a national survey of resident continuity clinic directors.

Science.gov (United States)

Nadkarni, Mohan; Reddy, Siddharta; Bates, Carol K; Fosburgh, Blair; Babbott, Stewart; Holmboe, Eric

2011-01-01

Many have called for ambulatory training redesign in internal medicine (IM) residencies to increase primary care career outcomes. Many believe dysfunctional, clinic environments are a key barrier to meaningful ambulatory education, but little is actually known about the educational milieu of continuity clinics nationwide. We wished to describe the infrastructure and educational milieu at resident continuity clinics and assess clinic readiness to meet new IM-RRC requirements. National survey of ACGME accredited IM training programs. Directors of academic and community-based continuity clinics. Two hundred and twenty-one out of 365 (62%) of clinic directors representing 49% of training programs responded. Wide variation amongst continuity clinics in size, structure and educational organization exist. Clinics below the 25th percentile of total clinic sessions would not meet RRC-IM requirements for total number of clinic sessions. Only two thirds of clinics provided a longitudinal mentor. Forty-three percent of directors reported their trainees felt stressed in the clinic environment and 25% of clinic directors felt overwhelmed. The survey used self reported data and was not anonymous. A slight predominance of larger clinics and university based clinics responded. Data may not reflect changes to programs made since 2008. This national survey demonstrates that the continuity clinic experience varies widely across IM programs, with many sites not yet meeting new ACGME requirements. The combination of disadvantaged and ill patients with inadequately resourced clinics, stressed residents, and clinic directors suggests that many sites need substantial reorganization and institutional commitment.New paradigms, encouraged by ACGME requirement changes such as increased separation of inpatient and outpatient duties are needed to improve the continuity clinic experience.

Are data from national quality registries used in quality improvement at Swedish hospital clinics?

Science.gov (United States)

Fredriksson, Mio; Halford, Christina; Eldh, Ann Catrine; Dahlström, Tobias; Vengberg, Sofie; Wallin, Lars; Winblad, Ulrika

2017-11-01

To investigate the use of data from national quality registries (NQRs) in local quality improvement as well as purported key factors for effective clinical use in Sweden. Comparative descriptive: a web survey of all Swedish hospitals participating in three NQRs with different levels of development (certification level). Heads of the clinics and physician(s) at clinics participating in the Swedish Stroke Register (Riksstroke), the Swedish National Registry of Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks) and the Swedish Lung Cancer Registry (NLCR). Individual and unit level use of NQRs in local quality improvement, and perceptions on data quality, organizational conditions and user motivation. Riksstroke data were reported as most extensively used at individual and unit levels (x̅ 17.97 of 24 and x̅ 27.06 of 35). Data quality and usefulness was considered high for the two most developed NQRs (x̅ 19.86 for Riksstroke and x̅ 19.89 for GallRiks of 25). Organizational conditions were estimated at the same level for Riksstroke and GallRiks (x̅ 12.90 and x̅ 13.28 of 20) while the least developed registry, the NLCR, had lower estimates (x̅ 10.32). In Riksstroke, the managers requested registry data more often (x̅ 15.17 of 20). While there were significant differences between registries in key factors such as management interest, use of NQR data in local quality improvement seems rather prevalent, at least for Riksstroke. The link between the registry's level of development and factors important for routinization of innovations such as NQRs needs investigation. © The Author 2017. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

The National Clinical Skills Competition Promotes the Construction of a Comprehensive Training Program for Chinese Medical Students

Science.gov (United States)

Yang, Jing; Huang, Si-min; Lu, Chun-ting; Feng, Lie

2018-01-01

To explore an efficient training program based on an analysis in organizing seven sessions for the National Clinical Skills Competition in China. Each year, 6-12 excellent medical students of our university are selected as an observation team. Comparisons of the teaching characteristics were performed in this study. An optimal curriculum…

Olfactory Function and Associated Clinical Correlates in Former National Football League Players

Science.gov (United States)

Alosco, Michael L.; Jarnagin, Johnny; Tripodis, Yorghos; Platt, Michael; Martin, Brett; Chaisson, Christine E.; Baugh, Christine M.; Fritts, Nathan G.; Cantu, Robert C.

2017-01-01

Abstract Professional American football players incur thousands of repetitive head impacts (RHIs) throughout their lifetime. The long-term consequences of RHI are not well characterized, but may include olfactory dysfunction. RHI has been associated with changes to brain regions involved in olfaction, and olfactory impairment is common after traumatic brain injury. Olfactory dysfunction is a frequent early sequelae of neurodegenerative diseases (e.g., Alzheimer's disease), and RHI is associated with the neurodegenerative disease, chronic traumatic encephalopathy (CTE). We examined olfaction, and its association with clinical measures, in former National Football League (NFL) players. Ninety-five former NFL players (ages 40–69) and 28 same-age controls completed a neuropsychological and neuropsychiatric evaluation as part of a National Institutes of Health–funded study. The Brief Smell Identification Test (B-SIT) assessed olfaction. Principal component analysis generated a four-factor structure of the clinical measures: behavioral/mood, psychomotor speed/executive function, and verbal and visual memory. Former NFL players had worse B-SIT scores relative to controls (p = 0.0096). A B-SIT cutoff of 11 had the greatest accuracy (c-statistic = 0.61) and specificity (79%) for discriminating former NFL players from controls. In the former NFL players, lower B-SIT scores correlated with greater behavioral/mood impairment (p = 0.0254) and worse psychomotor speed/executive functioning (p = 0.0464) after controlling for age and education. Former NFL players exhibited lower olfactory test scores relative to controls, and poorer olfactory test performance was associated with worse neuropsychological and neuropsychiatric functioning. Future work that uses more-comprehensive tests of olfaction and structural and functioning neuroimaging may improve understanding on the association between RHI and olfaction. PMID:27430424

Robustness studies of ignition targets for the National Ignition Facility in two dimensions

International Nuclear Information System (INIS)

Clark, Daniel S.; Haan, Steven W.; Salmonson, Jay D.

2008-01-01

Inertial confinement fusion capsules are critically dependent on the integrity of their hot spots to ignite. At the time of ignition, only a certain fractional perturbation of the nominally spherical hot spot boundary can be tolerated and the capsule still achieve ignition. The degree to which the expected hot spot perturbation in any given capsule design is less than this maximum tolerable perturbation is a measure of the ignition margin or robustness of that design. Moreover, since there will inevitably be uncertainties in the initial character and implosion dynamics of any given capsule, all of which can contribute to the eventual hot spot perturbation, quantifying the robustness of that capsule against a range of parameter variations is an important consideration in the capsule design. Here, the robustness of the 300 eV indirect drive target design for the National Ignition Facility [Lindl et al., Phys. Plasmas 11, 339 (2004)] is studied in the parameter space of inner ice roughness, implosion velocity, and capsule scale. A suite of 2000 two-dimensional simulations, run with the radiation hydrodynamics code LASNEX, is used as the data base for the study. For each scale, an ignition region in the two remaining variables is identified and the ignition cliff is mapped. In accordance with the theoretical arguments of Levedahl and Lindl [Nucl. Fusion 37, 165 (1997)] and Kishony and Shvarts [Phys. Plasmas 8, 4925 (2001)], the location of this cliff is fitted to a power law of the capsule implosion velocity and scale. It is found that the cliff can be quite well represented in this power law form, and, using this scaling law, an assessment of the overall (one- and two-dimensional) ignition margin of the design can be made. The effect on the ignition margin of an increase or decrease in the density of the target fill gas is also assessed

Clinical manifestation and aetiology of a genital associated disease in Olive baboons (Papio hamadryas anubis) at Lake Manyara National Park, Tanzania

OpenAIRE

Knauf, Sascha

2011-01-01

The aim of the study was to investigate a genitally associated disease and to describe its clinical manifestation and aetiology in baboons at Lake Manyara National Park in the United Republic of Tanzania. Lake Manyara National Park is located in the northern part of the country, 160 km northwest of the Mt. Kilimanjaro. It is among the smallest protected areas, but belongs to the extended ecosystem of the Serengeti, Ngorongoro Conservation Area, Lake Manyara and Tarangire National Park. The...

Outcome Measures for Clinical Trials in Down Syndrome.

Science.gov (United States)

Esbensen, Anna J; Hooper, Stephen R; Fidler, Deborah; Hartley, Sigan L; Edgin, Jamie; d'Ardhuy, Xavier Liogier; Capone, George; Conners, Frances A; Mervis, Carolyn B; Abbeduto, Leonard; Rafii, Michael; Krinsky-McHale, Sharon J; Urv, Tiina

2017-05-01

Increasingly individuals with intellectual and developmental disabilities, including Down syndrome, are being targeted for clinical trials. However, a challenge exists in effectively evaluating the outcomes of these new pharmacological interventions. Few empirically evaluated, psychometrically sound outcome measures appropriate for use in clinical trials with individuals with Down syndrome have been identified. To address this challenge, the National Institutes of Health (NIH) assembled leading clinicians and scientists to review existing measures and identify those that currently are appropriate for trials; those that may be appropriate after expansion of age range addition of easier items, and/or downward extension of psychometric norms; and areas where new measures need to be developed. This article focuses on measures in the areas of cognition and behavior.

Common data elements for clinical research in mitochondrial disease: a National Institute for Neurological Disorders and Stroke project

NARCIS (Netherlands)

Karaa, A.; Rahman, S.; Lombes, A.; Yu-Wai-Man, P.; Sheikh, M.K.; Alai-Hansen, S.; Cohen, B.H.; Dimmock, D.; Emrick, L.; Falk, M.J.; McCormack, S.; Mirsky, D.; Moore, T.; Parikh, S.; Shoffner, J.; Taivassalo, T.; Tarnopolsky, M.; Tein, I.; Odenkirchen, J.C.; Goldstein, A.; Koene, S.; Smeitink, J.A.M.; et al.,

2017-01-01

OBJECTIVES: The common data elements (CDE) project was developed by the National Institute of Neurological Disorders and Stroke (NINDS) to provide clinical researchers with tools to improve data quality and allow for harmonization of data collected in different research studies. CDEs have been

National objectives and flexible mechanisms: A discussions report

International Nuclear Information System (INIS)

Johansson, Bengt

2003-01-01

The Swedish climate policy has the target that the national emissions of greenhouse gases should be reduced 4%, compared to the 1990 level. But according to the EU common policy in line with the Kyoto agreement, Sweden has the right to increase the emissions by 4%. The Kyoto obligations could also be fulfilled by acting through the flexible mechanisms. In the present report the following issues are discussed: Why did Sweden set so ambitious targets; How can you handle the interconnection between national targets and flexible mechanisms; Methods to determine the amounts of the emissions rights that should be allocated to the trading sectors; Are there alternative means for achieving the targets that the national objectives have set

Implementing targeted region capture sequencing for the clinical detection of Alagille syndrome: An efficient and cost‑effective method.

Science.gov (United States)

Huang, Tianhong; Yang, Guilin; Dang, Xiao; Ao, Feijian; Li, Jiankang; He, Yizhou; Tang, Qiyuan; He, Qing

2017-11-01

Alagille syndrome (AGS) is a highly variable, autosomal dominant disease that affects multiple structures including the liver, heart, eyes, bones and face. Targeted region capture sequencing focuses on a panel of known pathogenic genes and provides a rapid, cost‑effective and accurate method for molecular diagnosis. In a Chinese family, this method was used on the proband and Sanger sequencing was applied to validate the candidate mutation. A de novo heterozygous mutation (c.3254_3255insT p.Leu1085PhefsX24) of the jagged 1 gene was identified as the potential disease‑causing gene mutation. In conclusion, the present study suggested that target region capture sequencing is an efficient, reliable and accurate approach for the clinical diagnosis of AGS. Furthermore, these results expand on the understanding of the pathogenesis of AGS.

Addressing key science and technology issues for IFE chambers, target fabrication and target injection

International Nuclear Information System (INIS)

Meier, W.R.; Goodin, D.T.; Nobile, A.

2003-01-01

Significant progress has been made in the development of high repetition rate chambers, target fabrication and injection for inertial fusion energy (IFE) for both heavy ion and laser drivers. Research is being conducted in a coordinated manner by national laboratories, universities and industry. This paper provides an overview of U.S. research activities and discusses how interface considerations (such as beam propagation and target survival during injection) impact design choices. (author)

Multi-MW accelerator target material properties under proton irradiation at Brookhaven National Laboratory linear isotope producer

Science.gov (United States)

Simos, N.; Ludewig, H.; Kirk, H.; Dooryhee, E.; Ghose, S.; Zhong, Z.; Zhong, H.; Makimura, S.; Yoshimura, K.; Bennett, J. R. J.; Kotsinas, G.; Kotsina, Z.; McDonald, K. T.

2018-05-01

The effects of proton beams irradiating materials considered for targets in high-power accelerator experiments have been studied using the Brookhaven National Laboratory's (BNL) 200 MeV proton linac. A wide array of materials and alloys covering a wide range of the atomic number (Z) are being scoped by the high-power accelerator community prompting the BNL studies to focus on materials representing each distinct range, i.e. low-Z, mid-Z and high-Z. The low range includes materials such as beryllium and graphite, the midrange alloys such as Ti-6Al-4V, gum metal and super-Invar and finally the high-Z range pure tungsten and tantalum. Of interest in assessing proton irradiation effects are (a) changes in physiomechanical properties which are important in maintaining high-power target functionality, (b) identification of possible limits of proton flux or fluence above which certain materials cease to maintain integrity, (c) the role of material operating temperature in inducing or maintaining radiation damage reversal, and (d) phase stability and microstructural changes. The paper presents excerpt results deduced from macroscopic and microscopic post-irradiation evaluation (PIE) following several irradiation campaigns conducted at the BNL 200 MeV linac and specifically at the isotope producer beam-line/target station. The microscopic PIE relied on high energy x-ray diffraction at the BNL NSLS X17B1 and NSLS II XPD beam lines. The studies reveal the dramatic effects of irradiation on phase stability in several of the materials, changes in physical properties and ductility loss as well as thermally induced radiation damage reversal in graphite and alloys such as super-Invar.

Anticipated Ethics and Regulatory Challenges in PCORnet: The National Patient-Centered Clinical Research Network.

Science.gov (United States)

Ali, Joseph; Califf, Robert; Sugarman, Jeremy

2016-01-01

PCORnet, the National Patient-Centered Clinical Research Network, seeks to establish a robust national health data network for patient-centered comparative effectiveness research. This article reports the results of a PCORnet survey designed to identify the ethics and regulatory challenges anticipated in network implementation. A 12-item online survey was developed by leadership of the PCORnet Ethics and Regulatory Task Force; responses were collected from the 29 PCORnet networks. The most pressing ethics issues identified related to informed consent, patient engagement, privacy and confidentiality, and data sharing. High priority regulatory issues included IRB coordination, privacy and confidentiality, informed consent, and data sharing. Over 150 IRBs and five different approaches to managing multisite IRB review were identified within PCORnet. Further empirical and scholarly work, as well as practical and policy guidance, is essential if important initiatives that rely on comparative effectiveness research are to move forward.

Interobserver variability of clinical target volume delineation in supra-diaphragmatic Hodgkin's disease. A multi-institutional experience

International Nuclear Information System (INIS)

Genovesi, Domenico; Cefaro, Giampiero Ausili; Vinciguerra, Annamaria

2011-01-01

To determine interobserver variability in clinical target volume (CTV) of supra-diaphragmatic Hodgkin's lymphoma. At the 2008 AIRO (Italian Society of Radiation Oncology) Meeting, the Radiation Oncology Department of Chieti proposed a multi-institutional contouring dummy-run of two cases of early stage supra-diaphragmatic Hodgkin's lymphoma after chemotherapy. Clinical history, diagnostics, and planning CT imaging were available on Chieti's radiotherapy website (www.radioterapia.unich.it). Participating centers were requested to delineate the CTV and submit it to the coordinating center. To quantify interobserver variability of CTV delineations, the total volume, craniocaudal, laterolateral, and anteroposterior diameters were calculated. A total of 18 institutions for case A and 15 institutions for case B submitted the targets. Case A presented significant variability in total volume (range: 74.1-1,157.1 cc), craniocaudal (range: 6.5-22.5 cm; median: 16.25 cm), anteroposterior (range: 5.04-14.82 cm; median: 10.28 cm), and laterolateral diameters (range: 8.23-22.88 cm; median: 15.5 cm). Mean CTV was 464.8 cc (standard deviation: 280.5 cc). Case B presented significant variability in total volume (range: 341.8-1,662 cc), cranio-caudal (range: 8.0-28.5 cm; median: 23 cm), anteroposterior (range: 7.9-1.8 cm; median: 11.1 cm), and laterolateral diameters (range: 12.9-24.0 cm; median: 18.8 cm). Mean CTV was 926.0 cc (standard deviation: 445.7 cc). This significant variability confirms the need to apply specific guidelines to improve contouring uniformity in Hodgkin's lymphoma. (orig.)

National comparison of {sup 131}I measurement among nuclear medicine clinics of eight countries

Energy Technology Data Exchange (ETDEWEB)

Olsovcova, Veronika, E-mail: volsovcova@cmi.c [Czech Metrology Institute, Radiova 1, Praha 10, 102 00 (Czech Republic); Iwahara, Akira [Laboratorio Nacional de Metrologia das Radiacoes Ionizantes, Instituto de Radioprotecao e Dosimetria, Av. Salvador Allende, s/no. Recreio, Rio de Janeiro, CEP 22780-160 Brazil (Brazil); Oropesa, Pilar [Centro de Isotopos, Ave. Monumental y Carretera La Rada, Km 31/2, Guanabacoa, Ciudad Habana (Cuba); Joseph, Leena; Ravindra, Anuradha [Bhabha Atomic Research Centre, Radiation Safety Systems Division, Trombay, Mumbai-400 085 (India); Ghafoori, Mostafa [SSDL, Agricultural, Medical and Industrial Research School (AMIRS). Nuclear Science and Technology Research Institute, AEOI, Karaj (Iran, Islamic Republic of); Son, Hye-Kyung [Radiation Safety Division, National Institute of Food and Drug Safety Evaluation, Korea Food and Drug Administration, 194 Tongilro, Eunpyung-Gu, Seoul, 122-704 (Korea, Republic of); Sahagia, Maria [Horia Hulubei National Institute of R and D for Physics and Engineering, POB MG-6, 077125 Bucharest (Romania); Tastan, Selma [Ankara University Medical Faculty, Department of Nuclear Medicine, Cebeci 06100, Ankara (Turkey); Zimmerman, Brian [Dosimetry and Medical Radiation Physics Section, International Atomic Energy Agency, P.O. Box 100, A-1400 Vienna (Austria); Ionizing Radiation Division, National Institute of Standards and Technology, Gaithersburg, MD 20899-8462 (United States)

2010-07-15

A generally applicable protocol for organizing comparisons among nuclear medicine clinics created within the IAEA project CRP E2.10.05 was tested in Brazil, Cuba, Czech Republic, India, Iran, Republic of Korea, Romania and Turkey in 2007. Comparisons of measurement of {sup 131}I were organized by local pilot laboratories with different backgrounds and levels of experience in this field. The results and experiences gained were compared and analyzed. A majority of results in each national comparison were within 10% of the reference value.

National Clinical Skills Competition: an effective simulation-based method to improve undergraduate medical education in China

Directory of Open Access Journals (Sweden)

Guanchao Jiang

2016-02-01

Full Text Available Background: The National Clinical Skills Competition has been held in China for 5 consecutive years since 2010 to promote undergraduate education reform and improve the teaching quality. The effects of the simulation-based competition will be analyzed in this study. Methods: Participation in the competitions and the compilation of the questions used in the competition finals are summarized, and the influence and guidance quality are further analyzed. Through the nationwide distribution of questionnaires in medical colleges, the effects of the simulation-based competition on promoting undergraduate medical education reform were evaluated. Results: The results show that approximately 450 students from more than 110 colleges (accounting for 81% of colleges providing undergraduate clinical medical education in China participated in the competition each year. The knowledge, skills, and attitudes were comprehensively evaluated by simulation-based assessment. Eight hundred and eighty copies of the questionnaires were distributed to 110 participating medical schools in 2015. In total, 752 valid responses were received across 95 schools. The majority of the interviewees agreed or strongly agreed that competition promoted the adoption of advanced educational principles (76.8%, updated the curriculum model and instructional methods (79.8%, strengthened faculty development (84.0%, improved educational resources (82.1%, and benefited all students (53.4%. Conclusions: The National Clinical Skills Competition is widely accepted in China. It has effectively promoted the reform and development of undergraduate medical education in China.

Comparative evaluation of PCR amplification of RLEP, 16S rRNA, rpoT and Sod A gene targets for detection of M. leprae DNA from clinical and environmental samples.

Science.gov (United States)

Turankar, Ravindra P; Pandey, Shradha; Lavania, Mallika; Singh, Itu; Nigam, Astha; Darlong, Joydeepa; Darlong, Fam; Sengupta, Utpal

2015-03-01

PCR assay is a highly sensitive, specific and reliable diagnostic tool for the identification of pathogens in many infectious diseases. Genome sequencing Mycobacterium leprae revealed several gene targets that could be used for the detection of DNA from clinical and environmental samples. The PCR sensitivity of particular gene targets for specific clinical and environmental isolates has not yet been established. The present study was conducted to compare the sensitivity of RLEP, rpoT, Sod A and 16S rRNA gene targets in the detection of M. leprae in slit skin smear (SSS), blood, soil samples of leprosy patients and their surroundings. Leprosy patients were classified into Paucibacillary (PB) and Multibacillary (MB) types. Ziehl-Neelsen (ZN) staining method for all the SSS samples and Bacteriological Index (BI) was calculated for all patients. Standard laboratory protocol was used for DNA extraction from SSS, blood and soil samples. PCR technique was performed for the detection of M. leprae DNA from all the above-mentioned samples. RLEP gene target was able to detect the presence of M. leprae in 83% of SSS, 100% of blood samples and in 36% of soil samples and was noted to be the best out of all other gene targets (rpoT, Sod A and 16S rRNA). It was noted that the RLEP gene target was able to detect the highest number (53%) of BI-negative leprosy patients amongst all the gene targets used in this study. Amongst all the gene targets used in this study, PCR positivity using RLEP gene target was the highest in all the clinical and environmental samples. Further, the RLEP gene target was able to detect 53% of blood samples as positive in BI-negative leprosy cases indicating its future standardization and use for diagnostic purposes. Copyright © 2015 Asian African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.

Estimating the global clinical burden of Plasmodium falciparum malaria in 2007.

Directory of Open Access Journals (Sweden)

Simon I Hay

2010-06-01

according to their relative uncertainty and replaced by surveillance-based estimates in the least certain half, 98% of the global clinical burden continued to be estimated by cartographic techniques.Cartographic approaches to burden estimation provide a globally consistent measure of malaria morbidity of known fidelity, and they represent the only plausible method in those malaria-endemic countries with nonfunctional national surveillance. Unacceptable uncertainty in the clinical burden of malaria in only four countries confounds our ability to evaluate needs and monitor progress toward international targets for malaria control at the global scale. National prevalence surveys in each nation would reduce this uncertainty profoundly. Opportunities for further reducing uncertainty in clinical burden estimates by hybridizing alternative burden estimation procedures are also evaluated.

Clinical application of Lin's biopsy grasper for intrauterine targeted biopsy and polypectomy during office hysteroscopy.

Science.gov (United States)

Cheng, Hsin-Yi; Lin, Bao-Liang; Tseng, Jen-Yu; Ueno, Kazunori; Nakada, Sakura

2018-06-01

Hysteroscopy has widely been used for diagnosis of the uterine cavity; however, target biopsy has often been difficult in part to the inherent limitations of ancillary instruments. Lin's biopsy grasper was specifically designed to work in conjunction with a flexible hysteroscope to obtain intrauterine biopsy under transabdominal sonography. Herein, we share our clinical experience in the management of endometrial abnormalities with the use of Lin's biopsy grasper during office-based hysteroscopy. From February 2006 to November 2016, the use of Lin's biopsy grasper for tissue biopsy was attempted on 126 cases. We retrospectively recorded and analyzed the patients' preoperative characteristics and biopsy outcomes to demonstrate the feasibility and efficacy of Lin's biopsy grasper. Out of the one hundred and twenty-six enrolled patients, satisfactory targeted biopsies were achieved; including high diagnostic rate (92.1%, with 116 cases confirmed histologically) and adequate tissue retrieval (77.8%, with 98 cases obtaining optimal specimen volume). All patients tolerated the procedure without analgesics or anesthesia. Diagnostic flexible hysteroscopy combined with the use of Lin's biopsy grasper has proven to be an effective tool for intrauterine evaluation and obtaining tissue sample. Copyright © 2018. Published by Elsevier B.V.

Differentiation vs. common targets in the climate change debate

International Nuclear Information System (INIS)

Dillon, J.

1997-01-01

A question of whether to impose common greenhouse gas emission targets and timetables on all nations was discussed. An examination of how different targets for different countries, based on national circumstances, might be implemented was presented, including a list of some of the factors that countries have put forward as criteria for differentiation. The advantages and disadvantages of a differentiated system of targets were described. It was argued that since the economic structures and the makeup of industries in any particular country are determining factors in the country's ability to reduce greenhouse gas emissions, not taking them into account is a certain invitation to failure. Developing countries, in particular, would benefit from a differentiated system of targets

National Target for South Asia Specialists. A Report.

Science.gov (United States)

National Council on Foreign Language and International Studies, New York, NY.

The South Asia Panel of the National Council on Foreign Languages and International Studies reports on the need for specialists in the languages and cultures of Afghanistan, Bangladesh, India, Nepal, Pakistan, Sri Lanka, Bhutan, and the Maldives. Two categories of specialists are discussed: (1) individuals in government, mission, etc., in…

Achieving the Renewable Energy Target for Jamaica

Directory of Open Access Journals (Sweden)

Abdullahi Olabode ABDULKADRI

2014-05-01

Full Text Available ieving the Renewable Energy Target for Jamaica Abstract: The high cost of energy in Jamaica, one of the highest in the Caribbean region, is usually cited as a hindrance to industrial development and efficiency, especially in the manufacturing sector. High energy cost is also considered to be a national energy security issue and the government is taking steps to ensure adequate supply of energy at affordable prices. In the current National Development Plan, the government has set a target for renewable energy sources to supply 20% of the country's energy need by the year 2030. Using a linear programing model of energy planning, we examine how realistically this target could be achieved. Our findings indicate that the 20% renewable energy target is technically achievable with the optimal plan showing a mixture of wind power, hydropower and bagasse power but no solar power. However, when the timeline for investment in new generating capacities that will ensure the attainment of the target is considered, it becomes highly improbable that the target will be met. This study fills the gap that exists in evidence-based analysis of energy policy in Jamaica.

National Institutes of Health Clinical Alerts and Advisories

Science.gov (United States)

... 22, 2004 NHLBI Stops Study Testing How Long Children with Sickle Cell Anemia Should Have Blood Transfusions to Prevent Stroke National ... 8, 2000 Periodic Transfusions Lower Stroke Risk in Children with Sickle Cell Anemia National Heart, Lung, and Blood Institute (NHLBI) September ...

Assessing Multiple Pathways for Achieving China’s National Emissions Reduction Target

Directory of Open Access Journals (Sweden)

Mingyue Wang

2018-06-01

Full Text Available In order to achieve China’s target of carbon intensity emissions reduction in 2030, there is a need to identify a scientific pathway and feasible strategies. In this study, we used stochastic frontier analysis method of energy efficiency, incorporating energy structure, economic structure, human capital, capital stock and potential energy efficiency to identify an efficient pathway for achieving emissions reduction target. We set up 96 scenarios including single factor scenarios and multi-factors combination scenarios for the simulation. The effects of each scenario on achieving the carbon intensity reduction target are then evaluated. It is found that: (1 Potential energy efficiency has the greatest contribution to the carbon intensity emissions reduction target; (2 they are unlikely to reach the 2030 carbon intensity reduction target of 60% by only optimizing a single factor; (3 in order to achieve the 2030 target, several aspects have to be adjusted: the fossil fuel ratio must be lower than 80%, and its average growth rate must be decreased by 2.2%; the service sector ratio in GDP must be higher than 58.3%, while the growth rate of non-service sectors must be lowered by 2.4%; and both human capital and capital stock must achieve and maintain a stable growth rate and a 1% increase annually in energy efficiency. Finally, the specific recommendations of this research were discussed, including constantly improved energy efficiency; the upgrading of China’s industrial structure must be accelerated; emissions reduction must be done at the root of energy sources; multi-level input mechanisms in overall levels of education and training to cultivate the human capital stock must be established; investment in emerging equipment and accelerate the closure of backward production capacity to accumulate capital stock.

Target designs for the Brookhaven National Laboratory 5-MW pulsed spallation neutron source

International Nuclear Information System (INIS)

Ludewig, H.; Todosow, M.; Powell, J.R.

1996-01-01

A feasibility study of a compact high power density target for a spallation neutron source was under-taken. The target arrangement consists primarily of heavy metal, with appropriate cooling passages. A high intensity proton beam of intermediate energy is directed at the target, where it interacts with the heavy metal nuclei. The subsequent spallation reactions produce several neutrons per proton resulting in an intense neutron source. The proton beam is assumed to havean energy of 5 MW, and to be cyclic with a repetition rate of 10Hz and 50Hz. The study was divided into two broad sections. First, an analysis of preliminary target designs was undertaken to ensure the overall feasibility of the concepts involved in the design and eventual construction of such a high power density target. Second, two proposed target designs, based on the first set of analyses, are investigated in more detail. Special care is taken to ensure that the neutron fluxes in the moderator are at the desired level no material compatibility problems exist,and the target is able to operate in a reliable and safe manner. Several target materials, coolant types, and target arrangements are investigated in the first section. The second section concentrates on a single target material and geometric arrangement. However, several structural material choices continue to be investigated with the aim of minimizing the effects of structural heating, and associated thermally induced stresses. In the final section the conclusions of this preliminary study are summarized

Clinicopathologic Analysis of Microscopic Extension in Lung Adenocarcinoma: Defining Clinical Target Volume for Radiotherapy

International Nuclear Information System (INIS)

Grills, Inga S.; Fitch, Dwight L.; Goldstein, Neal S.; Yan Di; Chmielewski, Gary W.; Welsh, Robert J.; Kestin, Larry L.

2007-01-01

Purpose: To determine the gross tumor volume (GTV) to clinical target volume margin for non-small-cell lung cancer treatment planning. Methods: A total of 35 patients with Stage T1N0 adenocarcinoma underwent wedge resection plus immediate lobectomy. The gross tumor size and microscopic extension distance beyond the gross tumor were measured. The nuclear grade and percentage of bronchoalveolar features were analyzed for association with microscopic extension. The gross tumor dimensions were measured on a computed tomography (CT) scan (lung and mediastinal windows) and compared with the pathologic dimensions. The potential coverage of microscopic extension for two different lung stereotactic radiotherapy regimens was evaluated. Results: The mean microscopic extension distance beyond the gross tumor was 7.2 mm and varied according to grade (10.1, 7.0, and 3.5 mm for Grade 1 to 3, respectively, p < 0.01). The 90th percentile for microscopic extension was 12.0 mm (13.0, 9.7, and 4.4 mm for Grade 1 to 3, respectively). The CT lung windows correlated better with the pathologic size than did the mediastinal windows (gross pathologic size overestimated by a mean of 5.8 mm; composite size [gross plus microscopic extension] underestimated by a mean of 1.2 mm). For a GTV contoured on the CT lung windows, the margin required to cover microscopic extension for 90% of the cases would be 9 mm (9, 7, and 4 mm for Grade 1 to 3, respectively). The potential microscopic extension dosimetric coverage (55 Gy) varied substantially between the stereotactic radiotherapy schedules. Conclusion: For lung adenocarcinomas, the GTV should be contoured using CT lung windows. Although a GTV based on the CT lung windows would underestimate the gross tumor size plus microscopic extension by only 1.2 mm for the average case, the clinical target volume expansion required to cover the microscopic extension in 90% of cases could be as large as 9 mm, although considerably smaller for high-grade tumors

Auto-segmentation of low-risk clinical target volume for head and neck radiation therapy.

Science.gov (United States)

Yang, Jinzhong; Beadle, Beth M; Garden, Adam S; Gunn, Brandon; Rosenthal, David; Ang, Kian; Frank, Steven; Williamson, Ryan; Balter, Peter; Court, Laurence; Dong, Lei

2014-01-01

To investigate atlas-based auto-segmentation methods to improve the quality of the delineation of low-risk clinical target volumes (CTVs) of unilateral tonsil cancers. Sixteen patients received intensity modulated radiation therapy for left tonsil tumors. These patients were treated by a total of 8 oncologists, who delineated all contours manually on the planning CT image. We chose 6 of the patients as atlas cases and used atlas-based auto-segmentation to map each the atlas CTV to the other 10 patients (test patients). For each test patient, the final contour was produced by combining the 6 individual segmentations from the atlases using the simultaneous truth and performance level estimation algorithm. In addition, for each test patient, we identified a single atlas that produced deformed contours best matching the physician's manual contours. The auto-segmented contours were compared with the physician's manual contours using the slice-wise Hausdorff distance (HD), the slice-wise Dice similarity coefficient (DSC), and a total volume overlap index. No single atlas consistently produced good results for all 10 test cases. The multiatlas segmentation achieved a good agreement between auto-segmented contours and manual contours, with a median slice-wise HD of 7.4 ± 1.0 mm, median slice-wise DSC of 80.2% ± 5.9%, and total volume overlap of 77.8% ± 3.3% over the 10 test cases. For radiation oncologists who contoured both the test case and one of the atlas cases, the best atlas for a test case had almost always been contoured by the oncologist who had contoured that test case, indicating that individual physician's practice dominated in target delineation and was an important factor in optimal atlas selection. Multiatlas segmentation may improve the quality of CTV delineation in clinical practice for unilateral tonsil cancers. We also showed that individual physician's practice was an important factor in selecting the optimal atlas for atlas-based auto

Target Diagnostic Instrument-Based Controls Framework for the National Ignition Facility

International Nuclear Information System (INIS)

Shelton, R; O'Brien, D; Nelson, J; Kamperschroer, J

2007-01-01

NIF target diagnostics are being developed to observe and measure the extreme physics of targets irradiated by the 192-beam laser. The response time of target materials can be on the order of 100ps--the time it takes light to travel 3 cm--temperatures more than 100 times hotter than the surface of the sun, and pressures that exceed 109 atmospheres. Optical and x-ray diagnostics were developed and fielded to observe and record the results of the first 4-beam experiments at NIF. Hard and soft x-ray spectra were measured, and time-integrated and gated x-ray images of hydrodynamics experiments were recorded. Optical diagnostics recorded backscatter from the target, and VISAR laser velocimetry measurements were taken of laser-shocked target surfaces. Additional diagnostics are being developed and commissioned to observe and diagnose ignition implosions, including various neutron and activation diagnostics. NIF's diagnostics are being developed at LLNL and with collaborators at other sites. To accommodate the growing number of target diagnostics, an Instrument-Based Controls hardware-software framework has been developed to facilitate development and ease integration into the NIF Integrated Computer Control System (ICCS). Individual WindowsXP PC controllers for each digitizer, power supply and camera (i.e., instruments) execute controls software unique to each instrument model. Each hardware-software controller manages a single instrument, in contrast to the complexity of combining all the controls software needed for a diagnostic into a single controller. Because of this simplification, controllers can be more easily tested on the actual hardware, evaluating all normal and off-normal conditions. Each target diagnostic is then supported by a number of instruments, each with its own hardware-software instrument-based controller. Advantages of the instrument-based control architecture and framework include reusability, testability, and improved reliability of the deployed

Target Diagnostic Instrument-Based Controls Framework for the National Ignition Facility

Energy Technology Data Exchange (ETDEWEB)

Shelton, R; O' Brien, D; Nelson, J; Kamperschroer, J

2007-05-07

NIF target diagnostics are being developed to observe and measure the extreme physics of targets irradiated by the 192-beam laser. The response time of target materials can be on the order of 100ps--the time it takes light to travel 3 cm--temperatures more than 100 times hotter than the surface of the sun, and pressures that exceed 109 atmospheres. Optical and x-ray diagnostics were developed and fielded to observe and record the results of the first 4-beam experiments at NIF. Hard and soft x-ray spectra were measured, and time-integrated and gated x-ray images of hydrodynamics experiments were recorded. Optical diagnostics recorded backscatter from the target, and VISAR laser velocimetry measurements were taken of laser-shocked target surfaces. Additional diagnostics are being developed and commissioned to observe and diagnose ignition implosions, including various neutron and activation diagnostics. NIF's diagnostics are being developed at LLNL and with collaborators at other sites. To accommodate the growing number of target diagnostics, an Instrument-Based Controls hardware-software framework has been developed to facilitate development and ease integration into the NIF Integrated Computer Control System (ICCS). Individual WindowsXP PC controllers for each digitizer, power supply and camera (i.e., instruments) execute controls software unique to each instrument model. Each hardware-software controller manages a single instrument, in contrast to the complexity of combining all the controls software needed for a diagnostic into a single controller. Because of this simplification, controllers can be more easily tested on the actual hardware, evaluating all normal and off-normal conditions. Each target diagnostic is then supported by a number of instruments, each with its own hardware-software instrument-based controller. Advantages of the instrument-based control architecture and framework include reusability, testability, and improved reliability of the

A centralized informatics infrastructure for the National Institute on Drug Abuse Clinical Trials Network

Science.gov (United States)

Pan, Jeng-Jong; Nahm, Meredith; Wakim, Paul; Cushing, Carol; Poole, Lori; Tai, Betty; Pieper, Carl F.

2009-01-01

Background Clinical trial networks were created to provide a sustaining infrastructure for the conduct of multisite clinical trials. As such, they must withstand changes in membership. Centralization of infrastructure including knowledge management, portfolio management, information management, process automation, work policies, and procedures in clinical research networks facilitates consistency and ultimately research. Purpose In 2005, the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) transitioned from a distributed data management model to a centralized informatics infrastructure to support the network’s trial activities and administration. We describe the centralized informatics infrastructure and discuss our challenges to inform others considering such an endeavor. Methods During the migration of a clinical trial network from a decentralized to a centralized data center model, descriptive data were captured and are presented here to assess the impact of centralization. Results We present the framework for the informatics infrastructure and evaluative metrics. The network has decreased the time from last patient-last visit to database lock from an average of 7.6 months to 2.8 months. The average database error rate decreased from 0.8% to 0.2%, with a corresponding decrease in the interquartile range from 0.04%–1.0% before centralization to 0.01%–0.27% after centralization. Centralization has provided the CTN with integrated trial status reporting and the first standards-based public data share. A preliminary cost-benefit analysis showed a 50% reduction in data management cost per study participant over the life of a trial. Limitations A single clinical trial network comprising addiction researchers and community treatment programs was assessed. The findings may not be applicable to other research settings. Conclusions The identified informatics components provide the information and infrastructure needed for our clinical trial

The national clinical audit of falls and bone health-secondary prevention of falls and fractures: a physiotherapy perspective.

Science.gov (United States)

Goodwin, Victoria; Martin, Finbarr C; Husk, Janet; Lowe, Derek; Grant, Robert; Potter, Jonathan

2010-03-01

To establish current physiotherapy practice in the secondary management of falls and fragility fractures compared with national guidance. Web-based national clinical audit. Acute trusts (n=157) and primary care trusts (n=146) in England, Wales and Northern Ireland. Data were collected on 5642 patients with non-hip fragility fractures and 3184 patients with a hip fracture. Those patients who were bedbound or who declined assessment or rehabilitation were excluded from the analysis. Results indicate that of those with non-hip fractures, 28% received a gait and balance assessment, 22% participated in an exercise programme, and 3% were shown how to get up from the floor. For those with a hip fracture, the results were 68%, 44% and 7%, respectively. Physiotherapists have a significant role to play in the secondary prevention of falls and fractures. However, along with managers and professional bodies, more must be done to ensure that clinical practice reflects the evidence base and professional standards.

Rexin-G, a targeted genetic medicine for cancer.

Science.gov (United States)

Gordon, Erlinda M; Hall, Frederick L

2010-05-01

Rexin-G, a tumor-targeted retrovector bearing a cytocidal cyclin G1 construct, is the first targeted gene therapy vector to gain fast track designation and orphan drug priorities for multiple cancer indications in the US. This review describes the major milestones in the clinical development of Rexin-G: from the molecular cloning and characterization of the human cyclin G1 proto-oncogene in 1994, to the design of the first knockout constructs and genetic engineering of the targeted delivery system from 1995 to 1997, through the initial proofs-of-concept, molecular pharmacology and toxicology studies of Rexin-G in preclinical cancer models from 1997 to 2001, to the pioneering clinical studies in humans from 2002 to 2004, which--together with the advancements in bioprocess development of high-potency clinical grade vectors circa 2005 - 2006--led to the accelerated approval of Rexin-G for all solid tumors by the Philippine FDA in 2007 and the rapid progression of clinical studies from 2007 to 2009 to the cusp of pivotal Phase III trials in the US. In recording the development of Rexin-G as a novel form of targeted biological therapy, this review also highlights important aspects of vector design engineering which served to overcome the physiological barriers to gene delivery as it addresses the key regulatory issues involved in the development of a targeted gene therapy product. Progressive clinical development of Rexin-G demonstrates the potential safety and efficacy of targeted genetic medicine, while validating the design engineering of the molecular biotechnology platform.

Effects of Achieving Target Measures in Rheumatoid Arthritis on Functional Status, Quality of Life, and Resource Utilization: Analysis of Clinical Practice Data.

Science.gov (United States)

Alemao, Evo; Joo, Seongjung; Kawabata, Hugh; Al, Maiwenn J; Allison, Paul D; Rutten-van Mölken, Maureen P M H; Frits, Michelle L; Iannaccone, Christine K; Shadick, Nancy A; Weinblatt, Michael E

2016-03-01

To evaluate associations between achieving guideline-recommended targets of disease activity, defined by the Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) Clinical Disease Activity Index (CDAI) ≤2.8, and other health outcomes in a longitudinal observational study. Other defined thresholds included low disease activity (LDA), moderate (MDA), or severe disease activity (SDA). To control for intraclass correlation and estimate effects of independent variables on outcomes of the modified Health Assessment Questionnaire (M-HAQ), the EuroQol 5-domain (EQ-5D; a quality-of-life measure), hospitalization, and durable medical equipment (DME) use, we employed mixed models for continuous outcomes and generalized estimating equations for binary outcomes. Among 1,297 subjects, achievement (versus nonachievement) of recommended disease targets was associated with enhanced physical functioning and lower health resource utilization. After controlling for baseline covariates, achievement of disease targets (versus LDA) was associated with significantly enhanced physical functioning based on SDAI ≤3.3 (ΔM-HAQ -0.047; P = 0.0100) and CDAI ≤2.8 (-0.073; P = 0.0003) but not DAS28-CRP measures was associated with enhanced physical functioning and health-related quality of life. Some health outcomes were similar in subjects attaining guideline targets versus LDA. Achieving LDA is a worthy clinical objective in some patients. © 2016 The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

AGS Spallation Target Experiment (ASTE) Collaboration

International Nuclear Information System (INIS)

Oyama, Yukio

1999-01-01

An experiment on mercury spallation target with high energy proton beam, called as the AGS Spallation Target Experiment (ASTE) Collaboration, has been performed at Alternating Gradient Synchrotron (AGS) of Brookhaven National Laboratory (BNL) in USA, in cooperation among the laboratories in Japan, Europe and USA. The experimental setup, scope and preliminary results are presented in the paper. (author)

Clinical practice guidelines in complementary and alternative medicine. An analysis of opportunities and obstacles. Practice and Policy Guidelines Panel, National Institutes of Health Office of Alternative Medicine.

Science.gov (United States)

1997-01-01

An estimated 1 of 3 Americans uses some form of complementary and alternative medicine (CAM), such as acupuncture, homeopathy, or herbal medicine. In 1995, the National Institutes of Health Office of Alternative Medicine convened an expert panel to examine the role of clinical practice guidelines in CAM. The panel concluded that CAM practices currently are unsuitable for the development of evidence-based practice guidelines, in part because of the lack of relevant outcomes data from well-designed clinical trials. Moreover, the notions of standardization and appropriateness, inherent in guideline development, face challenging methodologic problems when applied to CAM, which considers many different treatment practices appropriate and encourages highly individualized care. Due to different belief systems and divergent theories about the nature of health and illness, CAM disciplines have fundamental differences in how they define target conditions, causes of disease, interventions, and outcome measures of effectiveness. These differences are even more striking when compared with those used by Western medicine. The panel made a series of recommendations on strategies to strengthen the evidence base for future guideline development in CAM and to meet better the current information needs of clinicians, patients, and guideline developers who seek information about CAM treatments.

Conceptual design report for the University of Rochester cryogenic target delivery system

International Nuclear Information System (INIS)

Fagaly, R.L.; Alexander, N.B.; Bourque, R.F.; Dahms, C.F.; Lindgren, J.R.; Miller, W.J.; Bittner, D.N.; Hendricks, C.D.

1993-05-01

The upgrade of the Omega laser at the University of Rochester's Laboratory for Laser Energetics (UR/LLE) will result in a need for large targets filled with D 2 or Dt and maintained at cryogenic temperatures. This mandates a cryogenic target delivery system capable of filling, layering, characterizing and delivering cryogenic targets to the Omega Upgrade target chamber. The program goal is to design, construct, and test the entire target delivery system by June 1996. When completed (including an operational demonstration), the system will be shipped to Rochester for reassembly and commissioning in time for the Omega Upgrade cryogenic campaign, scheduled to start in 1998. General Atomics has been assigned the task of developing the conceptual design for the cryogenic target delivery system. Design and fabrication activities will be closely coordinated with the University of Rochester, Lawrence Livermore National laboratory (LLNL) and Los Alamos National Laboratory (LANL), drawing upon their knowledge base in fuel layering and cryogenic characterization. The development of a target delivery system for Omega could also benefit experiments at Lawrence Livermore National Laboratory and the other ICF Laboratories in that the same technologies could be applied to NOVA, the National Ignition Facility or the future Laboratory Microfusion Facility

Conceptual design report for the University of Rochester cryogenic target delivery system

Energy Technology Data Exchange (ETDEWEB)

Fagaly, R.L.; Alexander, N.B.; Bourque, R.F.; Dahms, C.F.; Lindgren, J.R.; Miller, W.J. (General Atomics, San Diego, CA (United States)); Bittner, D.N.; Hendricks, C.D. (W.J. Schafer Associates, Livermore, CA (United States))

1993-05-01

The upgrade of the Omega laser at the University of Rochester's Laboratory for Laser Energetics (UR/LLE) will result in a need for large targets filled with D[sub 2] or Dt and maintained at cryogenic temperatures. This mandates a cryogenic target delivery system capable of filling, layering, characterizing and delivering cryogenic targets to the Omega Upgrade target chamber. The program goal is to design, construct, and test the entire target delivery system by June 1996. When completed (including an operational demonstration), the system will be shipped to Rochester for reassembly and commissioning in time for the Omega Upgrade cryogenic campaign, scheduled to start in 1998. General Atomics has been assigned the task of developing the conceptual design for the cryogenic target delivery system. Design and fabrication activities will be closely coordinated with the University of Rochester, Lawrence Livermore National laboratory (LLNL) and Los Alamos National Laboratory (LANL), drawing upon their knowledge base in fuel layering and cryogenic characterization. The development of a target delivery system for Omega could also benefit experiments at Lawrence Livermore National Laboratory and the other ICF Laboratories in that the same technologies could be applied to NOVA, the National Ignition Facility or the future Laboratory Microfusion Facility.

Conceptual design report for the University of Rochester cryogenic target delivery system

Energy Technology Data Exchange (ETDEWEB)

Fagaly, R.L.; Alexander, N.B.; Bourque, R.F.; Dahms, C.F.; Lindgren, J.R.; Miller, W.J. [General Atomics, San Diego, CA (United States); Bittner, D.N.; Hendricks, C.D. [W.J. Schafer Associates, Livermore, CA (US)

1993-05-01

The upgrade of the Omega laser at the University of Rochester`s Laboratory for Laser Energetics (UR/LLE) will result in a need for large targets filled with D{sub 2} or Dt and maintained at cryogenic temperatures. This mandates a cryogenic target delivery system capable of filling, layering, characterizing and delivering cryogenic targets to the Omega Upgrade target chamber. The program goal is to design, construct, and test the entire target delivery system by June 1996. When completed (including an operational demonstration), the system will be shipped to Rochester for reassembly and commissioning in time for the Omega Upgrade cryogenic campaign, scheduled to start in 1998. General Atomics has been assigned the task of developing the conceptual design for the cryogenic target delivery system. Design and fabrication activities will be closely coordinated with the University of Rochester, Lawrence Livermore National laboratory (LLNL) and Los Alamos National Laboratory (LANL), drawing upon their knowledge base in fuel layering and cryogenic characterization. The development of a target delivery system for Omega could also benefit experiments at Lawrence Livermore National Laboratory and the other ICF Laboratories in that the same technologies could be applied to NOVA, the National Ignition Facility or the future Laboratory Microfusion Facility.

SANDS: a service-oriented architecture for clinical decision support in a National Health Information Network.

Science.gov (United States)

Wright, Adam; Sittig, Dean F

2008-12-01

In this paper, we describe and evaluate a new distributed architecture for clinical decision support called SANDS (Service-oriented Architecture for NHIN Decision Support), which leverages current health information exchange efforts and is based on the principles of a service-oriented architecture. The architecture allows disparate clinical information systems and clinical decision support systems to be seamlessly integrated over a network according to a set of interfaces and protocols described in this paper. The architecture described is fully defined and developed, and six use cases have been developed and tested using a prototype electronic health record which links to one of the existing prototype National Health Information Networks (NHIN): drug interaction checking, syndromic surveillance, diagnostic decision support, inappropriate prescribing in older adults, information at the point of care and a simple personal health record. Some of these use cases utilize existing decision support systems, which are either commercially or freely available at present, and developed outside of the SANDS project, while other use cases are based on decision support systems developed specifically for the project. Open source code for many of these components is available, and an open source reference parser is also available for comparison and testing of other clinical information systems and clinical decision support systems that wish to implement the SANDS architecture. The SANDS architecture for decision support has several significant advantages over other architectures for clinical decision support. The most salient of these are:

Comparative evaluation of PCR amplification of RLEP, 16S rRNA, rpoT and Sod A gene targets for detection of M. leprae DNA from clinical and environmental samples

Directory of Open Access Journals (Sweden)

Ravindra P Turankar

2015-01-01

Conclusion: Amongst all the gene targets used in this study, PCR positivity using RLEP gene target was the highest in all the clinical and environmental samples. Further, the RLEP gene target was able to detect 53% of blood samples as positive in BI-negative leprosy cases indicating its future standardization and use for diagnostic purposes.

The National Ignition Facility

International Nuclear Information System (INIS)

Hogan, W.J.; Moses, E.; Warner, B.; Sorem, M.; Soures, J.M.

2001-01-01

The National Ignition Facility (NIF) is the largest construction project ever undertaken at Lawrence Livermore National Laboratory (LLNL). NIF consists of 192 forty-centimeter-square laser beams and a 10-m-diameter target chamber. NIF is being designed and built by an LLNL-led team from Los Alamos National Laboratory, Sandia National Laboratories, the University of Rochester, and LLNL. Physical construction began in 1997. The Laser and Target Area Building and the Optics Assembly Building were the first major construction activities, and despite several unforeseen obstacles, the buildings are now 92% complete and have been done on time and within cost. Prototype component development and testing has proceeded in parallel. Optics vendors have installed full-scale production lines and have done prototype production runs. The assembly and integration of the beampath infrastructure has been reconsidered and a new approach has been developed. This paper will discuss the status of the NIF project and the plans for completion. (author)

Preclinical studies and clinical trial of targeted alpha therapy for cancer

International Nuclear Information System (INIS)

Allen, B.J.

2002-01-01

Full text: Targeted Alpha therapy (TAT) offers the potential to inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The practicality and efficacy of TAT is tested by in vitro and in vivo studies in melanoma, leukemia, colorectal, breast and prostate cancers. Materials and Methods: The alpha-emitting radioisotope is Bi-213, which is produced by the Ac-225 generator and chelated to a cancer specific monoclonal antibody (mab) or protein (eg plasmmogen activator inhibitor PAI2) to form the alpha-conjugate (AC). Stable alpha-ACs have been produced which have been tested for specificity and cytotoxicity in vitro against melanoma (9.2.27 mab), leukemia (WM60 mab), colorectal (C30.6 mab), breast (PAI2) and prostate (PAI2, J591 mab) cancers. Subcutaneous inoculation of 1-1.5 million human cancer cells into the flanks of nude mice causes tumours to grow in all mice. Tumour growth is compared for untreated controls, nonspecific AC and specific AC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. Results: In vitro studies show that TAT is one to two orders of magnitude more cytotoxic to targeted cells than nonspecific ACs, specific beta emitting conjugates or free isotope. In vivo local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Intra-lesional TAT can also completely regress advanced sc melanomas but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of sc melanoma xenografts and gives almost complete control of breast and prostate cancer tumour growth. Conclusions: These results point to the application of local and systemic TAT in the management of secondary cancer. A phase 1 and 2 clinical trial of TAT of subcutaneous, secondary melanoma has commenced at St George Hospital, and 10/30 subjects have been treated by intralesional injection

Proposed definition of the vaginal cuff and paracolpium clinical target volume in postoperative uterine cervical cancer.

Science.gov (United States)

Murakami, Naoya; Norihisa, Yoshiki; Isohashi, Fumiaki; Murofushi, Keiko; Ariga, Takuro; Kato, Tomoyasu; Inaba, Koji; Okamoto, Hiroyuki; Ito, Yoshinori; Toita, Takafumi; Itami, Jun

2016-01-01

The aim of this study was to develop an appropriate definition for vaginal cuff and paracolpium clinical target volume (CTV) for postoperative intensity modulated radiation therapy in patients with uterine cervical cancer. A working subgroup was organized within the Radiation Therapy Study Group of the Japan Clinical Oncology Group to develop a definition for the postoperative vaginal cuff and paracolpium CTV in December 2013. The group consisted of 5 radiation oncologists who specialized in gynecologic oncology and a gynecologic oncologist. A comprehensive literature review that included anatomy, surgery, and imaging fields was performed and was followed by multiple discreet face-to-face discussions and e-mail messages before a final consensus was reached. Definitions for the landmark structures in all directions that demarcate the vaginal cuff and paracolpium CTV were decided by consensus agreement of the working group. A table was created that showed boundary structures of the vaginal cuff and paracolpium CTV in each direction. A definition of the postoperative cervical cancer vaginal cuff and paracolpium CTV was developed. It is expected that this definition guideline will serve as a template for future radiation therapy clinical trial protocols, especially protocols involving intensity modulated radiation therapy. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Socioeconomic inequalities in prognostic markers of non-Hodgkin lymphoma: analysis of a national clinical database

DEFF Research Database (Denmark)

Frederiksen, Birgitte Lidegaard; Brown, Peter de Nully; Dalton, Susanne Oksbjerg

2011-01-01

in histological subgroups reflecting aggressiveness of disease among the social groups. One of the most likely mechanisms of the social difference is longer delay in those with low socioeconomic position. The findings of social inequality in prognostic markers in non-Hodgkin lymphoma (NHL) patients could already......The survival of non-Hodgkin lymphoma patients strongly depends on a range of prognostic factors. This registry-based clinical cohort study investigates the relation between socioeconomic position and prognostic markers in 6234 persons included in a national clinical database in 2000-2008, Denmark....... Several measures of individual socioeconomic position were achieved from Statistics Denmark. The risk of being diagnosed with advanced disease, as expressed by the six prognostic markers (Ann Arbor stage III or IV, more than one extranodal lesion, elevated serum lactate dehydrogenase (LDH), performance...

Exploring the Educational Value of Clinical Vignettes from the Society of General Internal Medicine National Meeting in the Internal Medicine Clerkship

Science.gov (United States)

Wofford, James L; Singh, Sonal

2006-01-01

INTRODUCTION Whether the clinical vignettes presented at the Society of General Internal Medicine (SGIM) annual meeting could be of educational value to third year students in the Internal Medicine clerkship has not been studied. OBJECTIVE To explore the relevance and learning value of clinical vignettes from the SGIM national meeting in the Internal Medicine clerkship. SETTING Third year Ambulatory Internal Medicine clerkship at one academic medical center (academic year 2005 to 2006). METHODS Students were introduced to the clinical vignette and oriented to the database of clinical vignettes available through the SGIM annual meeting website. Students then reviewed 5 to 10 clinical vignettes using a worksheet, and rated the learning value of each vignette using a 5-point Likert scale (1 = least, 5 = greatest). A single investigator evaluated congruence of the vignette with the Clerkship Directors of Internal Medicine (CDIM)-SGIM curriculum to assess relevance. MAIN RESULTS A total of 42 students evaluated 371 clinical vignettes from the 2004 and 2005 meetings. The clinical vignettes were curriculum-congruent in 42.6% (n = 175), and clearly incongruent in 40.4% (n = 164). The mean rating for learning value was 3.8 (±1.0) (5 signifying greatest learning value). Curriculum-congruent vignettes had a higher mean learning value compared with curriculum-incongruent vignettes (4.0 vs 3.6, Student's t-test, P =.017). CONCLUSION The clinical vignettes presented at the national SGIM meeting offer clinical content that is relevant and of some educational value for third year clerkship students. Based on this pilot study, the educational value and strategies for their use in the clinical clerkships deserve further study. PMID:17026730

'Treat to Target' - Lessons Learnt.

Science.gov (United States)

Kurti, Zsuzsanna; Vegh, Zsuzsanna; Golovics, Petra Anna; Lakatos, Peter Laszlo

2016-01-01

Therapeutic management in inflammatory bowel diseases (IBD) has significantly changed in the last decades with the advent of biological therapy resulting in new treatment targets other than clinical symptoms. Patient stratification in the early stage of the disease is an important step to identify patients with poor prognosis, who might benefit from early aggressive treatment to avoid complications in the later disease course. Recent randomized and hypothesis driven (e.g., Randomized Evaluation of an Algorithm for Crohn's Treatment, Post-Operative Crohn's Endoscopic Recurrence) clinical trials conducted in the biological era underscore the need of objective disease monitoring including assessment of biomarkers (e.g., C-reactive protein and calprotectin), mucosal healing and, for biologically treated patients, therapeutic drug monitoring beside clinical symptom assessment in both Crohn's disease and ulcerative colitis. Assessing the treatment efficacy objectively has become an important element of patient monitoring besides clinical symptom assessment. Further clinical studies are needed to assess whether implementation of new therapeutic algorithms based on these targets and tight monitoring in clinical practice have the potential to further improve long-term disease outcomes in IBD. © 2016 S. Karger AG, Basel.

A parent-report Gender Identity Questionnaire for Children: A cross-national, cross-clinic comparative analysis.

Science.gov (United States)

Cohen-Kettenis, Peggy T; Wallien, Madeleine; Johnson, Laurel L; Owen-Anderson, Allison F H; Bradley, Susan J; Zucker, Kenneth J

2006-07-01

A one-factor, 14-item parent-report Gender Identity Questionnaire for Children (GIQC) was developed in a sample of 325 clinic-referred children with gender identity problems and 504 controls from Toronto, Canada (Johnson et al., 2004). In this study, we report a cross-national, cross-clinic comparative analysis of the GIQC on gender-referred children (N = 338) from Toronto and gender-referred children (N = 175) from Utrecht, The Netherlands. Across clinics, the results showed both similarities and differences. Gender-referred boys from Utrecht had a significantly higher total score (indicating more cross-gender behavior) than did gender-referred boys from Toronto, but there was no significant difference for girls. In the Toronto sample, the gender-referred girls had a significantly higher total score than the gender-referred boys, but there was no significant sex difference in the Utrecht sample. Across both clinics, gender-referred children who met the complete DSM criteria for gender identity disorder (GID) had a significantly higher cross-gender score than the gender-referred children who were subthreshold for GID (Cohen's d = 1.11). The results of this study provide the first empirical evidence of relative similarity in cross-gender behavior in a sample of gender-referred children from western Europe when compared to North American children. The results also provide some support for cross-clinic consistency in clinician-based diagnosis of GID.

Immunohistochemical evaluation of molecular radiotherapy target expression in neuroblastoma tissue

Energy Technology Data Exchange (ETDEWEB)

Gains, Jennifer E.; Gaze, Mark N. [University College London Hospitals NHS Foundation Trust, Department of Oncology, London (United Kingdom); Sebire, Neil J. [Great Ormond Street Hospital for Children NHS Foundation Trust, Department of Pathology, London (United Kingdom); Moroz, Veronica; Wheatley, Keith [University of Birmingham, Cancer Research UK Clinical Trials Unit, Birmingham (United Kingdom)

2018-03-15

Neuroblastoma may be treated with molecular radiotherapy, {sup 131}I meta-Iodobenzylguanidine and {sup 177}Lu Lutetium DOTATATE, directed at distinct molecular targets: Noradrenaline Transporter Molecule (NAT) and Somatostatin Receptor (SSTR2), respectively. This study used immunohistochemistry to evaluate target expression in archival neuroblastoma tissue, to determine whether it might facilitate clinical use of molecular radiotherapy. Tissue bank samples of formalin fixed paraffin embedded neuroblastoma tissue from patients for whom clinical outcome data were available were sectioned and stained with haematoxylin and eosin, and monoclonal antibodies directed against NAT and SSTR2. Sections were examined blinded to clinical information and scored for the percentage and intensity of tumour cells stained. These data were analysed in conjunction with clinical data. Tissue from 75 patients was examined. Target expression scores varied widely between patients: NAT median 45%, inter-quartile range 25% - 65%; and SSTR2 median 55%, interquartile range 30% - 80%; and in some cases heterogeneity of expression between different parts of a tumour was observed. A weak positive correlation was observed between the expression scores of the different targets: correlation coefficient = 0.23, p = 0.05. MYCN amplified tumours had lower SSTR2 scores: mean difference 23% confidence interval 8% - 39%, p < 0.01. Survival did not differ by scores. As expression of both targets is variable and heterogeneous, imaging assessment of both may yield more clinical information than either alone. The clinical value of immunohistochemical assessment of target expression requires prospective evaluation. Variable target expression within a patient may contribute to treatment failure. (orig.)

High-efficiency target-ion sources for RIB generation

International Nuclear Information System (INIS)

Alton, G.D.

1993-01-01

A brief review is given of high-efficiency ion sources which have been developed or are under development at ISOL facilities which show particular promise for use at existing, future, or radioactive ion beam (RIB) facilities now under construction. Emphasis will be placed on those sources which have demonstrated high ionization efficiency, species versatility, and operational reliability and which have been carefully designed for safe handling in the high level radioactivity radiation fields incumbent at such facilities. Brief discussions will also be made of the fundamental processes which affect the realizable beam intensities in target-ion sources. Among the sources which will be reviewed will be selected examples of state-of-the-art electron-beam plasma-type ion sources, thermal-ionization, surface-ionization, ECR, and selectively chosen ion source concepts which show promise for radioactive ion beam generation. A few advanced, chemically selective target-ion sources will be described, such as sources based on the use of laser-resonance ionization, which, in principle, offer a more satisfactory solution to isobaric contamination problems than conventional electromagnetic techniques. Particular attention will be given to the sources which have been selected for initial or future use at the Holifield Radioactive Ion Beam Facility now under construction at the Oak Ridge National Laboratory

Target biomarker profile for the clinical management of paracetamol overdose

Science.gov (United States)

Vliegenthart, A D Bastiaan; Antoine, Daniel J; Dear, James W

2015-01-01

Paracetamol (acetaminophen) overdose is one of the most common causes of acute liver injury in the Western world. To improve patient care and reduce pressure on already stretched health care providers new biomarkers are needed that identify or exclude liver injury soon after an overdose of paracetamol is ingested. This review highlights the current state of paracetamol poisoning management and how novel biomarkers could improve patient care and save healthcare providers money. Based on the widely used concept of defining a target product profile, a target biomarker profile is proposed that identifies desirable and acceptable key properties for a biomarker in development to enable the improved treatment of this patient population. The current biomarker candidates, with improved hepatic specificity and based on the fundamental mechanistic basis of paracetamol-induced liver injury, are reviewed and their performance compared with our target profile. PMID:26076366

Targeted treatment for chronic lymphocytic leukemia: clinical potential of obinutuzumab

Directory of Open Access Journals (Sweden)

Smolej L

2014-12-01

Full Text Available Lukáš Smolej 4th Department of Internal Medicine – Hematology, University Hospital Hradec Králové and Charles University in Prague, Faculty of Medicine in Hradec Králové, Hradec Králové, Czech Republic Abstract: Introduction of targeted agents revolutionized the treatment of chronic lymphocytic leukemia (CLL in the past decade. Addition of chimeric monoclonal anti-CD20 antibody rituximab to chemotherapy significantly improved efficacy including overall survival (OS in untreated fit patients; humanized anti-CD52 antibody alemtuzumab and fully human anti-CD20 antibody ofatumumab lead to improvement in refractory disease. Novel small molecule inhibitors such as ibrutinib and idelalisib demonstrated excellent activity and were very recently licensed in relapsed/refractory CLL. Obinutuzumab (GA101 is the newest monoclonal antibody approved for the treatment of CLL. This novel, glycoengineered, type II humanized anti-CD20 antibody is characterized by enhanced antibody-dependent cellular cytotoxicity and direct induction of cell death compared to type I antibodies. Combination of obinutuzumab and chlorambucil yielded significantly better OS in comparison to chlorambucil monotherapy in untreated comorbid patients. These results led to approval of obinuzutumab for the treatment of CLL. Numerous clinical trials combining obinutuzumab with other cytotoxic drugs and novel small molecules are currently under way. This review focuses on the role of obinutuzumab in the treatment of CLL. Keywords: chronic lymphocytic leukemia, anti-CD20 antibodies, chlorambucil, rituximab, ofatumumab, obinutuzumab, overall survival

Clinical Trials

Medline Plus

Full Text Available ... about your health or fill out forms about how you feel. Some people will need to travel or stay in hospitals to take part in clinical trials. For example, the National Institutes of Health Clinical Center in Bethesda, Maryland, runs clinical trials. Many other clinical trials take place ...

National Ignition Facility subsystem design requirements target diagnostics subsystem SSDR 1.8.3

International Nuclear Information System (INIS)

Lee, D.

1996-01-01

This SSDR establishes the performance, design, development and test requirements for the Target Experimental System's Diagnostic, WBS 1.8. 3. This includes the individual diagnostic components, the Target Diagnostic Data Acquisition System (Target DAS), the diagnostic vacuum system, the timing/fiducial system, and the EMI protection system

Canadian Chronic Kidney Disease Clinics: A National Survey of Structure, Function and Models of Care

Directory of Open Access Journals (Sweden)

Adeera Levin

2014-11-01

Full Text Available Background: The goals of care for patients with chronic kidney disease (CKD are to delay progression to end stage renal disease, reduce complications, and to ensure timely transition to dialysis or transplantation, while optimizing independence. Recent guidelines recommend that multidisciplinary team based care should be available to patients with CKD. While most provinces fund CKD care, the specific models by which these outcomes are achieved are not known. Funding for clinics is hospital or program based. Objectives: To describe the structure and function of clinics in order to understand the current models of care, inform best practice and potentially standardize models of care. Design: Prospective cross sectional observational survey study. Setting, Patients/Participants: Canadian nephrology programs in all provinces. Methods and Measurements: Using an open-ended semi-structured questionnaire, we surveyed 71 of 84 multidisciplinary adult CKD clinics across Canada, by telephone and with written semi-structured questionnaires; (June 2012 to November 2013. Standardized introductory scripts were used, in both English and French. Results: CKD clinic structure and models of care vary significantly across Canada. Large variation exists in staffing ratios (Nephrologist, dieticians, pharmacists and nurses to patients, and in referral criteria. Dialysis initiation decisions were usually made by MDs. The majority of clinics (57% had a consistent model of care (the same Nephrologist and nurse per patient, while others had patients seeing a different nephrologist and nurses at each clinic visit. Targets for various modality choices varied, as did access to those modalities. No patient or provider educational tools describing the optimal time to start dialysis exist in any of the clinics. Limitations: The surveys rely on self reporting without validation from independent sources, and there was limited involvement of Quebec clinics. These are relative

Dissemination and Implementation Research Funded by the US National Institutes of Health, 2005–2012

OpenAIRE

Tinkle, Mindy; Kimball, Richard; Haozous, Emily A.; Shuster, George; Meize-Grochowski, Robin

2013-01-01

Dissemination and implementation (D&I) research is a growing area of science focused on overcoming the science-practice gap by targeting the distribution of information and adoption of interventions to public health and clinical practice settings. This study examined D&I research projects funded under specific program announcements by the US National Institutes of Health (NIH) from 2005 to 2012. The authors described the projects' D&I strategies, funding by NIH Institute, focus, characteristi...

Clinical target volume delineation including elective nodal irradiation in preoperative and definitive radiotherapy of pancreatic cancer

Directory of Open Access Journals (Sweden)

Caravatta Luciana

2012-06-01

Full Text Available Abstract Background Radiotherapy (RT is widely used in the treatment of pancreatic cancer. Currently, recommendation has been given for the delineation of the clinical target volume (CTV in adjuvant RT. Based on recently reviewed pathologic data, the aim of this study is to propose criteria for the CTV definition and delineation including elective nodal irradiation (ENI in the preoperative and definitive treatment of pancreatic cancer. Methods The anatomical structures of interest, as well as the abdominal vasculature were identified on intravenous contrast-enhanced CT scans of two different patients with pancreatic cancer of the head and the body. To delineate the lymph node area, a margin of 10 mm was added to the arteries. Results We proposed a set of guidelines for elective treatment of high-risk nodal areas and CTV delineation. Reference CT images were provided. Conclusions The proposed guidelines could be used for preoperative or definitive RT for carcinoma of the head and body of the pancreas. Further clinical investigations are needed to validate the defined CTVs.

Treatment of adult patients with schizophrenia and complex mental health needs - A national clinical guideline

DEFF Research Database (Denmark)

Baandrup, Lone; Østrup Rasmussen, Jesper; Klokker, Louise

2016-01-01

BACKGROUND AND AIM: The Danish Health and Medicines Authority assembled a group of experts to develop a national clinical guideline for patients with schizophrenia and complex mental health needs. Within this context, ten explicit review questions were formulated, covering several identified key...... therapy for persistent positive and/or negative symptoms, and the combination of cognitive behavioural therapy and motivational interviewing for cannabis and/or central stimulant abuse. SSRI or SNRI add-on treatment for persistent negative symptoms should be used only cautiously. Where no evidence...

A national survey on pediatric critical values used in clinical laboratories across Canada.

Science.gov (United States)

Gong, Yanping; Adeli, Khosrow

2009-11-01

Notification of critical values to clinical staff is an important post-analytical process in all acute care clinical laboratories. No data are available however on how laboratories obtain or establish critical values, particularly in pediatric settings. This study was designed to examine and compare critical values used for pediatric patients in biochemistry laboratories in Canada and assess potential interlaboratory variability. Fourteen clinical laboratories, including two in pediatric hospitals and twelve in hospitals caring for both children and adults, participated in a survey that included 14 pre-selected STAT chemistry tests and 19 pre-selected therapeutic drug monitoring (TDM) tests. Among fourteen chemistry tests, good agreement was observed for critical values used for sodium and pH at both low and high levels within 14 participant laboratories. Significant interlaboratory variability existed for glucose critical values at the high end, magnesium at high end, and PO2 at the low end. For 19 TDM tests, the majority of laboratories did not have alert values to report values over the therapeutic level but not toxic. For critical values greater than the toxic range, significant variability existed at both trough and peak levels among laboratories surveyed. When asked to provide the source for critical values established at each site, only a limited number of laboratories identified their sources as either internal decision or published references. Although all laboratories have established and routinely use critical values to alert clinical staff, considerable variability exists in both the critical limits reported as well as the source of such values. There is a clear need for new national efforts to standardize pediatric critical value reporting and establish evidence-based critical limits for all medical laboratories across Canada.

Clinical trial network for the promotion of clinical research for rare diseases in Japan: muscular dystrophy clinical trial network.

Science.gov (United States)

Shimizu, Reiko; Ogata, Katsuhisa; Tamaura, Akemi; Kimura, En; Ohata, Maki; Takeshita, Eri; Nakamura, Harumasa; Takeda, Shin'ichi; Komaki, Hirofumi

2016-07-11

Duchenne muscular dystrophy (DMD) is the most commonly inherited neuromuscular disease. Therapeutic agents for the treatment of rare disease, namely "orphan drugs", have recently drawn the attention of researchers and pharmaceutical companies. To ensure the successful conduction of clinical trials to evaluate novel treatments for patients with rare diseases, an appropriate infrastructure is needed. One of the effective solutions for the lack of infrastructure is to establish a network of rare diseases. To accomplish the conduction of clinical trials in Japan, the Muscular dystrophy clinical trial network (MDCTN) was established by the clinical research group for muscular dystrophy, including the National Center of Neurology and Psychiatry, as well as national and university hospitals, all which have a long-standing history of research cooperation. Thirty-one medical institutions (17 national hospital organizations, 10 university hospitals, 1 national center, 2 public hospitals, and 1 private hospital) belong to this network and collaborate to facilitate clinical trials. The Care and Treatment Site Registry (CTSR) calculates and reports the proportion of patients with neuromuscular diseases in the cooperating sites. In total, there are 5,589 patients with neuromuscular diseases in Japan and the proportion of patients with each disease is as follows: DMD, 29 %; myotonic dystrophy type 1, 23 %; limb girdle muscular dystrophy, 11 %; Becker muscular dystrophy, 10 %. We work jointly to share updated health care information and standardized evaluations of clinical outcomes as well. The collaboration with the patient registry (CTSR), allows the MDCTN to recruit DMD participants with specific mutations and conditions, in a remarkably short period of time. Counting with a network that operates at a national level is important to address the corresponding national issues. Thus, our network will be able to contribute with international research activity, which can lead to

Clinical utility and development of biomarkers in invasive aspergillosis.

Science.gov (United States)

Patterson, Thomas F

2011-01-01

The diagnosis of invasive aspergillosis remains very difficult, and there are limited treatment options for the disease. Pre-clinical models have been used to evaluate the diagnosis and treatment of Aspergillus infection and to assess the pathogenicity and virulence of the organism. Extensive efforts in Aspergillus research have significantly expanded the genomic information about this microorganism. The standardization of animal models of invasive aspergillosis can be used to enhance the evaluation of genomic information about the organism to improve the diagnosis and treatment of invasive aspergillosis. One approach to this process has been the award of a contract by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health to establish and standardize animal models of invasive aspergillosis for the development of new diagnostic technologies for both pulmonary and disseminated Aspergillus infection. This work utilizes molecular approaches for the genetic manipulation of Aspergillus strains that can be tested in animal-model systems to establish new diagnostic targets and tools. Studies have evaluated the performance characteristics of assays for cell-wall antigens of Aspergillus including galactomannan and beta-D-glucan, as well as for DNA targets in the organism, through PCR. New targets, such as proteomic and genomic approaches, and novel detection methods, such as point-of-care lateral-flow devices, have also been evaluated. The goal of this paper is to provide a framework for evaluating genomic targets in animal models to improve the diagnosis and treatment of invasive aspergillosis toward ultimately improving the outcomes for patients with this frequently fatal infection.

Real-time non-rigid target tracking for ultrasound-guided clinical interventions

NARCIS (Netherlands)

Zachiu, Cornel; Ries, Mario G; Ramaekers, Pascal; Guey, Jean-Luc; Moonen, Chrit T W; de Senneville, Baudouin Denis

2017-01-01

Biological motion is a problem for non- or mini-invasive interventions when conducted in mobile/deformable organs due to the targeted pathology moving/deforming with the organ. This may lead to high miss rates and/or incomplete treatment of the pathology. Therefore, real-time tracking of the target

Clinical Trials

Medline Plus

Full Text Available ... need to travel or stay in hospitals to take part in clinical trials. For example, the National Institutes of Health Clinical Center in ... Maryland, runs clinical trials. Many other clinical trials take place in medical centers and ... trial can have many benefits. For example, you may gain access to new treatments before ...

Overview of the Los Alamos National Laboratory Inertial Confinement Fusion Program

International Nuclear Information System (INIS)

Harris, D.B.

1991-01-01

The Los Alamos Inertial Confinement Fusion (ICF) Program is focused on preparing for a National Ignition Facility. Target physics research is addressing specific issues identified for the Ignition Facility target, and materials experts are developing target fabrication techniques necessary for the advanced targets. We are also working with Lawrence Livermore National Laboratory on the design of the National Ignition Facility target chamber. Los Alamos is also continuing to develop the KrF laser-fusion driver for ICF. We are modifying the Aurora laser to higher intensity and shorter pulses and are working with the Naval Research Laboratory on the development of the Nike KrF laser. 9 refs., 1 fig., 2 tabs

What margins should be added to the clinical target volume in radiotherapy treatment planning of lung cancer?

International Nuclear Information System (INIS)

Ekberg, L.; Wittgren, L.; Holmberg, O.

1995-01-01

When defining the planning target volume (PTV) in radiotherapy treatment planning, it is vital to add geometrical margins of normal tissue around the clinical target volume (CTV). This is to ensure that the whole CTV will receive the planned absorbed dose taking into account both set-up deviations and target movements as well as other geometrical variations in the treatment chain. The problem is our limited knowledge of how large these margins should be. To assess the size of needed margins around the CTV in conformal radiotherapy of lung cancer, electronic portal imaging was employed in 232 irradiation field set-ups of 14 patients. This was done in order to quantify the uncertainty in the execution of treatment considering patient movement and set-up displacements. For an estimation of the added geometrical variation from target movement during irradiation, fluoroscopy was used at the simulation of the irradiation fields. The set-up study showed an average systematic deviation for all individual fields of 3.1 mm and an average maximal systematic deviation (in either transversal or craniocaudal direction) of 4.8 mm. The random errors can be described by an average standard deviation of 2.8 mm for all fields in either direction. Major gradual displacements as a function of time was also detected in one of the patients. CTV-movements of several millimetres during respiration could be observed. It was also seen that heartbeats could add to CTV-movements during irradiation with an equal magnitude. The combined effect of these factors are considered when making an overall estimation of margins that should be added to the CTV

Development and Mechanism of Small Activating RNA Targeting CEBPA, a Novel Therapeutic in Clinical Trials for Liver Cancer.

Science.gov (United States)

Voutila, Jon; Reebye, Vikash; Roberts, Thomas C; Protopapa, Pantelitsa; Andrikakou, Pinelopi; Blakey, David C; Habib, Robert; Huber, Hans; Saetrom, Pal; Rossi, John J; Habib, Nagy A

2017-12-06

Small activating RNAs (saRNAs) are short double-stranded oligonucleotides that selectively increase gene transcription. Here, we describe the development of an saRNA that upregulates the transcription factor CCATT/enhancer binding protein alpha (CEBPA), investigate its mode of action, and describe its development into a clinical candidate. A bioinformatically directed nucleotide walk around the CEBPA gene identified an saRNA sequence that upregulates CEBPA mRNA 2.5-fold in human hepatocellular carcinoma cells. A nuclear run-on assay confirmed that this upregulation is a transcriptionally driven process. Mechanistic experiments demonstrate that Argonaute-2 (Ago2) is required for saRNA activity, with the guide strand of the saRNA shown to be associated with Ago2 and localized at the CEBPA genomic locus using RNA chromatin immunoprecipitation (ChIP) assays. The data support a sequence-specific on-target saRNA activity that leads to enhanced CEBPA mRNA transcription. Chemical modifications were introduced in the saRNA duplex to prevent activation of the innate immunity. This modified saRNA retains activation of CEBPA mRNA and downstream targets and inhibits growth of liver cancer cell lines in vitro. This novel drug has been encapsulated in a liposomal formulation for liver delivery, is currently in a phase I clinical trial for patients with liver cancer, and represents the first human study of an saRNA therapeutic. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Single Centre Experience – Clinical Presentation and Frequency of Paediatric Diabetic Ketoacidosis (DKA) At Diagnosis over a 5-Year Period

LENUS (Irish Health Repository)

McKenna, A

2018-03-01

Type 1 diabetes (T1D) symptoms are subtle and easily overlooked. Delayed diagnosis can result in Diabetic ketoacidosis (DKA), a life threatening complication with lasting consequences. We sought to define the presenting features of T1D and DKA frequency, in children <15 years diagnosed in a single national tertiary centre, and identify predictive factors for DKA. A review of T1D incident cases was undertaken from 2008-2012 using the National Diabetes Register (ICDNR) and clinical case notes. Data were compared with a 1997\\/8 national study. We found DKA at presentation in 28.7 % of children and 15.5% had moderate\\/severe DKA. Commonest symptoms were polydipsia, polyuria, weight loss, and lethargy. Median symptom duration was 17 days. Clinical presentation was similar and frequency of DKA at T1D diagnosis remains high. The proportion with moderate\\/severe DKA is lower than the 25% previously reported (p=0.038). National monitoring and targeted action to reduce DKA at diagnosis is required.

Simple model of the indirect compression of targets under conditions close to the national ignition facility at an energy of 1.5 MJ

Energy Technology Data Exchange (ETDEWEB)

Rozanov, V. B., E-mail: rozanov@sci.lebedev.ru; Vergunova, G. A., E-mail: verg@sci.lebedev.ru [Russian Academy of Sciences, Lebedev Physical Institute (Russian Federation)

2015-11-15

The possibility of the analysis and interpretation of the reported experiments with the megajoule National Ignition Facility (NIF) laser on the compression of capsules in indirect-irradiation targets by means of the one-dimensional RADIAN program in the spherical geometry has been studied. The problem of the energy balance in a target and the determination of the laser energy that should be used in the spherical model of the target has been considered. The results of action of pulses differing in energy and time profile (“low-foot” and “high-foot” regimes) have been analyzed. The parameters of the compression of targets with a high-density carbon ablator have been obtained. The results of the simulations are in satisfactory agreement with the measurements and correspond to the range of the observed parameters. The set of compared results can be expanded, in particular, for a more detailed determination of the parameters of a target near the maximum compression of the capsule. The physical foundation of the possibility of using the one-dimensional description is the necessity of the closeness of the last stage of the compression of the capsule to a one-dimensional process. The one-dimensional simulation of the compression of the capsule can be useful in establishing the boundary behind which two-dimensional and three-dimensional simulation should be used.

Anatomic Boundaries of the Clinical Target Volume (Prostate Bed) After Radical Prostatectomy

International Nuclear Information System (INIS)

Wiltshire, Kirsty L.; Brock, Kristy K.; Haider, Masoom A.; Zwahlen, Daniel; Kong, Vickie; Chan, Elisa; Moseley, Joanne; Bayley, Andrew; Catton, Charles; Chung, Peter W.M.; Gospodarowicz, Mary; Milosevic, Michael; Kneebone, Andrew; Warde, Padraig; Menard, Cynthia

2007-01-01

Purpose: We sought to derive and validate an interdisciplinary consensus definition for the anatomic boundaries of the postoperative clinical target volume (CTV, prostate bed). Methods and Materials: Thirty one patients who had planned for radiotherapy after radical prostatectomy were enrolled and underwent computed tomography and magnetic resonance imaging (MRI) simulation prior to radiotherapy. Through an iterative process of consultation and discussion, an interdisciplinary consensus definition was derived based on a review of published data, patterns of local failure, surgical practice, and radiologic anatomy. In validation, we analyzed the distribution of surgical clips in reference to the consensus CTV and measured spatial uncertainties in delineating the CTV and vesicourethral anastomosis. Clinical radiotherapy plans were retrospectively evaluated against the consensus CTV (prostate bed). Results: Anatomic boundaries of the consensus CTV (prostate bed) are described. Surgical clips (n = 339) were well distributed throughout the CTV. The vesicourethral anastomosis was accurately localized using central sagittal computed tomography reconstruction, with a mean ± standard deviation uncertainty of 1.8 ± 2.5 mm. Delineation uncertainties were small for both MRI and computed tomography (mean reproducibility, 0-3.8 mm; standard deviation, 1.0-2.3); they were most pronounced in the anteroposterior and superoinferior dimensions and at the superior/posterior-most aspect of the CTV. Retrospectively, the mean ± standard deviation CTV (prostate bed) percentage of volume receiving 100% of prescribed dose was only 77% ± 26%. Conclusions: We propose anatomic boundaries for the CTV (prostate bed) and present evidence supporting its validity. In the absence of gross recurrence, the role of MRI in delineating the CTV remains to be confirmed. The CTV is larger than historically practiced at our institution and should be encompassed by a microscopic tumoricidal dose

Projected national impact of colorectal cancer screening on clinical and economic outcomes and health services demand.

Science.gov (United States)

Ladabaum, Uri; Song, Kenneth

2005-10-01

Colorectal cancer (CRC) screening is effective and cost-effective, but the potential national impact of widespread screening is uncertain. It is controversial whether screening colonoscopy can be offered widely and how emerging tests may impact health services demand. Our aim was to produce integrated, comprehensive estimates of the impact of widespread screening on national clinical and economic outcomes and health services demand. We used a Markov model and census data to estimate the national consequences of screening 75% of the US population with conventional and emerging strategies. Screening decreased CRC incidence by 17%-54% to as few as 66,000 cases per year and CRC mortality by 28%-60% to as few as 23,000 deaths per year. With no screening, total annual national CRC-related expenditures were 8.4 US billion dollars. With screening, expenditures for CRC care decreased by 1.5-4.4 US billion dollars but total expenditures increased to 9.2-15.4 US billion dollars. Screening colonoscopy every 10 years required 8.1 million colonoscopies per year including surveillance, with other strategies requiring 17%-58% as many colonoscopies. With improved screening uptake, total colonoscopy demand increased in general, even assuming substantial use of virtual colonoscopy. Despite savings in CRC care, widespread screening is unlikely to be cost saving and may increase national expenditures by 0.8-2.8 US billion dollars per year with conventional tests. The current national endoscopic capacity, as recently estimated, may be adequate to support widespread use of screening colonoscopy in the steady state. The impact of emerging tests on colonoscopy demand will depend on the extent to which they replace screening colonoscopy or increase screening uptake in the population.

National Ignition Facility subsystem design requirements target area auxiliary subsystem SSDR 1.8.6

International Nuclear Information System (INIS)

Reitz, T.

1996-01-01

This Subsystem Design Requirement (SSDR) establishes the performance, design, development, and test requirements for the Target Area Auxiliary Subsystems (WBS 1.8.6), which is part of the NIF Target Experimental System (WBS 1.8). This document responds directly to the requirements detailed in NIF Target Experimental System SDR 003 document. Key elements of the Target Area Auxiliary Subsystems include: WBS 1.8.6.1 Local Utility Services; WBS 1.8.6.2 Cable Trays; WBS 1.8.6.3 Personnel, Safety, and Occupational Access; WBS 1.8.6.4 Assembly, Installation, and Maintenance Equipment; WBS 1.8.6.4.1 Target Chamber Service System; WBS 1.8.6.4.2 Target Bay Service Systems

Tumor Vessel Development and Expansion in Ewing's Sarcoma: A Review of the Vasculogenesis Process and Clinical Trials with Vascular-Targeting Agents

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Stewart, Keri S.; Kleinerman, Eugenie S.

2011-01-01

Ewing's sarcoma accounts for a disproportionately high portion of the overall pediatric mortality rate compared to its rare incidence in the pediatric population. Little progress has been made since the introduction of traditional chemotherapies, and understanding the biology of the tumor is critical for developing new therapies. Ewing's sarcomas rely on a functional vascular supply, which is formed by a combination of angiogenesis and vasculogenesis. Recent insights into the molecular regulation of bone marrow (BM) cell participation in vascular development have identified VEGF, SDF-1α, and DLL4 as critical players in the vasculogenesis process. Clinical trials using vascular targeting agents, specifically targeting VEGF or DLL4, are underway. PMID:21785569

Targeting cancer stem cells: emerging role of Nanog transcription factor

Directory of Open Access Journals (Sweden)

Wang ML

2013-09-01

Full Text Available Mong-Lien Wang,1 Shih-Hwa Chiou,2,3 Cheng-Wen Wu1,4–61Institute of Biochemistry and Molecular Biology, 2Institute of Pharmacology, National Yang Ming University, Taipei, Taiwan; 3Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan; 4Institute of Microbiology and Immunology, 5Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan; 6Institute of Biomedical Science, Academia Sinica, Taipei, TaiwanAbstract: The involvement of stemness factors in cancer initiation and progression has drawn much attention recently, especially after the finding that introducing four stemness factors in somatic cells is able to reprogram the cells back to an embryonic stem cell-like state. Following accumulating data revealing abnormal elevated expression levels of key stemness factors, like Nanog, Oct4, and Sox2, in several types of cancer stem cells; the importance and therapeutic potential of targeting these stemness regulators in cancers has turned to research focus. Nanog determines cell fate in both embryonic and cancer stem cells; activating Nanog at an inappropriate time would result in cancer stem cells rather than normal pluripotent stem cells or differentiated somatic cells. Upregulated Nanog is correlated with poor survival outcome of patients with various types of cancer. The discoveries of downstream regulatory pathways directly or indirectly mediated by Nanog indicate that Nanog regulates several aspects of cancer development such as tumor cell proliferation, self-renewal, motility, epithelial-mesenchymal transition, immune evasion, and drug-resistance, which are all defined features for cancer stem cells. The current review paper illustrates the central role of Nanog in the regulatory networks of cancer malignant development and stemness acquirement, as well as in the communication between cancer cells and the surrounding stroma. Though a more defined model is needed to test the

Screening mammography. A missed clinical opportunity? Results of the NCI [National Cancer Institute] Breast Cancer Screening Consortium and national health interview survey studies

International Nuclear Information System (INIS)

Anon.

1990-01-01

Data from seven studies sponsored by the National Cancer Institute (NCI) were used to determine current rates of breast cancer screening and to identify the characteristics of and reasons for women not being screened. All seven studies were population-based surveys of women aged 50 to 74 years without breast cancer. While over 90% of non-Hispanic white respondents had regular sources of medical care, 46% to 76% had a clinical breast examination within the previous year, and only 25% to 41% had a mammogram. Less educated and poorer women had fewer mammograms. The two most common reasons women gave for never having had a mammogram were that they did not known they needed it and that their physician had not recommended it. Many physicians may have overlooked the opportunity to recommend mammography for older women when performing a clinical breast examination and to educate their patients about the benefit of screening mammography

Molecular Composition Analysis of Distant Targets

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National Aeronautics and Space Administration — We propose a system capable of probing the molecular composition of cold solar system targets such as asteroids, comets, planets and moons from a distant vantage....

Burglar Target Selection

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Townsley, Michael; Bernasco, Wim; Ruiter, Stijn; Johnson, Shane D.; White, Gentry; Baum, Scott

2015-01-01

Objectives: This study builds on research undertaken by Bernasco and Nieuwbeerta and explores the generalizability of a theoretically derived offender target selection model in three cross-national study regions. Methods: Taking a discrete spatial choice approach, we estimate the impact of both environment- and offender-level factors on residential burglary placement in the Netherlands, the United Kingdom, and Australia. Combining cleared burglary data from all study regions in a single statistical model, we make statistical comparisons between environments. Results: In all three study regions, the likelihood an offender selects an area for burglary is positively influenced by proximity to their home, the proportion of easily accessible targets, and the total number of targets available. Furthermore, in two of the three study regions, juvenile offenders under the legal driving age are significantly more influenced by target proximity than adult offenders. Post hoc tests indicate the magnitudes of these impacts vary significantly between study regions. Conclusions: While burglary target selection strategies are consistent with opportunity-based explanations of offending, the impact of environmental context is significant. As such, the approach undertaken in combining observations from multiple study regions may aid criminology scholars in assessing the generalizability of observed findings across multiple environments. PMID:25866418

Predictors of Academic Success for the National Board Dental Hygiene Examination and the Southern Regional Testing Agency Clinical Exam

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Efurd, Melissa G.

2012-01-01

The purpose for conducting this study was to investigate and describe the relationship between applicant criteria for a dental hygiene program and subsequent outcomes on credentialing exams: the National Board Dental Hygiene Exam and the Southern Regional Testing Agency clinical exam. Because admission criteria play a crucial role in applicant…

Targeting Accuracy, Procedure Times and User Experience of 240 Experimental MRI Biopsies Guided by a Clinical Add-On Navigation System.

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Busse, Harald; Riedel, Tim; Garnov, Nikita; Thörmer, Gregor; Kahn, Thomas; Moche, Michael

2015-01-01

MRI is of great clinical utility for the guidance of special diagnostic and therapeutic interventions. The majority of such procedures are performed iteratively ("in-and-out") in standard, closed-bore MRI systems with control imaging inside the bore and needle adjustments outside the bore. The fundamental limitations of such an approach have led to the development of various assistance techniques, from simple guidance tools to advanced navigation systems. The purpose of this work was to thoroughly assess the targeting accuracy, workflow and usability of a clinical add-on navigation solution on 240 simulated biopsies by different medical operators. Navigation relied on a virtual 3D MRI scene with real-time overlay of the optically tracked biopsy needle. Smart reference markers on a freely adjustable arm ensured proper registration. Twenty-four operators - attending (AR) and resident radiologists (RR) as well as medical students (MS) - performed well-controlled biopsies of 10 embedded model targets (mean diameter: 8.5 mm, insertion depths: 17-76 mm). Targeting accuracy, procedure times and 13 Likert scores on system performance were determined (strong agreement: 5.0). Differences in diagnostic success rates (AR: 93%, RR: 88%, MS: 81%) were not significant. In contrast, between-group differences in biopsy times (AR: 4:15, RR: 4:40, MS: 5:06 min:sec) differed significantly (p<0.01). Mean overall rating was 4.2. The average operator would use the system again (4.8) and stated that the outcome justifies the extra effort (4.4). Lowest agreement was reported for the robustness against external perturbations (2.8). The described combination of optical tracking technology with an automatic MRI registration appears to be sufficiently accurate for instrument guidance in a standard (closed-bore) MRI environment. High targeting accuracy and usability was demonstrated on a relatively large number of procedures and operators. Between groups with different expertise there were

Targeting Accuracy, Procedure Times and User Experience of 240 Experimental MRI Biopsies Guided by a Clinical Add-On Navigation System.

Directory of Open Access Journals (Sweden)

Harald Busse

Full Text Available MRI is of great clinical utility for the guidance of special diagnostic and therapeutic interventions. The majority of such procedures are performed iteratively ("in-and-out" in standard, closed-bore MRI systems with control imaging inside the bore and needle adjustments outside the bore. The fundamental limitations of such an approach have led to the development of various assistance techniques, from simple guidance tools to advanced navigation systems. The purpose of this work was to thoroughly assess the targeting accuracy, workflow and usability of a clinical add-on navigation solution on 240 simulated biopsies by different medical operators.Navigation relied on a virtual 3D MRI scene with real-time overlay of the optically tracked biopsy needle. Smart reference markers on a freely adjustable arm ensured proper registration. Twenty-four operators - attending (AR and resident radiologists (RR as well as medical students (MS - performed well-controlled biopsies of 10 embedded model targets (mean diameter: 8.5 mm, insertion depths: 17-76 mm. Targeting accuracy, procedure times and 13 Likert scores on system performance were determined (strong agreement: 5.0.Differences in diagnostic success rates (AR: 93%, RR: 88%, MS: 81% were not significant. In contrast, between-group differences in biopsy times (AR: 4:15, RR: 4:40, MS: 5:06 min:sec differed significantly (p<0.01. Mean overall rating was 4.2. The average operator would use the system again (4.8 and stated that the outcome justifies the extra effort (4.4. Lowest agreement was reported for the robustness against external perturbations (2.8.The described combination of optical tracking technology with an automatic MRI registration appears to be sufficiently accurate for instrument guidance in a standard (closed-bore MRI environment. High targeting accuracy and usability was demonstrated on a relatively large number of procedures and operators. Between groups with different expertise there were

Prostate bed target interfractional motion using RTOG consensus definitions and daily CT on rails. Does target motion differ between superior and inferior portions of the clinical target volume

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Verma, Vivek; Zhou, Sumin; Enke, Charles A.; Wahl, Andrew O. [University of Nebraska Medical Center, Department of Radiation Oncology, Omaha (United States); Chen, Shifeng [University of Maryland School of Medicine, Department of Radiation Oncology, Baltimore, MD (United States)

2017-01-15

Using high-quality CT-on-rails imaging, the daily motion of the prostate bed clinical target volume (PB-CTV) based on consensus Radiation Therapy Oncology Group (RTOG) definitions (instead of surgical clips/fiducials) was studied. It was assessed whether PB motion in the superior portion of PB-CTV (SUP-CTV) differed from the inferior PB-CTV (INF-CTV). Eight pT2-3bN0-1M0 patients underwent postprostatectomy intensity-modulated radiotherapy, totaling 300 fractions. INF-CTV and SUP-CTV were defined as PB-CTV located inferior and superior to the superior border of the pubic symphysis, respectively. Daily pretreatment CT-on-rails images were compared to the planning CT in the left-right (LR), superoinferior (SI), and anteroposterior (AP) directions. Two parameters were defined: ''total PB-CTV motion'' represented total shifts from skin tattoos to RTOG-defined anatomic areas; ''PB-CTV target motion'' (performed for both SUP-CTV and INF-CTV) represented shifts from bone to RTOG-defined anatomic areas (i. e., subtracting shifts from skin tattoos to bone). Mean (± standard deviation, SD) total PB-CTV motion was -1.5 (± 6.0), 1.3 (± 4.5), and 3.7 (± 5.7) mm in LR, SI, and AP directions, respectively. Mean (± SD) PB-CTV target motion was 0.2 (±1.4), 0.3 (±2.4), and 0 (±3.1) mm in the LR, SI, and AP directions, respectively. Mean (± SD) INF-CTV target motion was 0.1 (± 2.8), 0.5 (± 2.2), and 0.2 (± 2.5) mm, and SUP-CTV target motion was 0.3 (± 1.8), 0.5 (± 2.3), and 0 (± 5.0) mm in LR, SI, and AP directions, respectively. No statistically significant differences between INF-CTV and SUP-CTV motion were present in any direction. There are no statistically apparent motion differences between SUP-CTV and INF-CTV. Current uniform planning target volume (PTV) margins are adequate to cover both portions of the CTV. (orig.) [German] Zur Evaluation der interfraktionellen Variabilitaet des klinischen Zielvolumens der Prostataloge

Assessing Clinical Research Capacity in Vietnam: A Framework for Strengthening Capability for Clinical Trials in Developing Countries.

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Kagan, Jonathan; Giang, Dao Duc; Iademarco, Michael F; Phung, Van Tt; Lau, Chuen-Yen; Quang, Nguyen Ngo

2016-01-01

Although improving health systems promises important benefits, most developing nations lack the resources to support nationally driven clinical research. Strengthened clinical research capacity can advance national health goals by supporting greater autonomy in aligning research with national priorities. From March through June 2010, we assessed six elements of clinical research capacity in Vietnam: research agenda; clinical investigators and biostatisticians; donors and sponsors; community involvement; scientific, ethical, safety, and quality oversight; and clinical research institutions. Assessments were drawn from interviews with investigators, Ministry of Health staff members, nongovernment organizations, and U.S. Mission staff members, and document review. Observations and recommendations were shared with collaborators. Reassessment in 2015 found growth in the number of clinical trials, improved regulation in human subjects protection and community engagement, and modest advances in research agenda setting. Training and investment in institutions remain challenging. A framework for assessing clinical research capacity can affirm strengths and weaknesses and guide the coordination of capacity-building efforts.

Targeting chemokine (C-C motif) ligand 2 (CCL2) as an example of translation of cancer molecular biology to the clinic.

Science.gov (United States)

Zhang, Jian; Patel, Lalit; Pienta, Kenneth J

2010-01-01

Chemokines are a family of small and secreted proteins that play pleiotropic roles in inflammation-related pathological diseases, including cancer. Among the identified 50 human chemokines, chemokine (C-C motif) ligand 2 (CCL2) is of particular importance in cancer development since it serves as one of the key mediators of interactions between tumor and host cells. CCL2 is produced by cancer cells and multiple different host cells within the tumor microenvironment. CCL2 mediates tumorigenesis in many different cancer types. For example, CCL2 has been reported to promote prostate cancer cell proliferation, migration, invasion, and survival, via binding to its functional receptor CCR2. Furthermore, CCL2 induces the recruitment of macrophages and induces angiogenesis and matrix remodeling. Targeting CCL2 has been demonstrated as an effective therapeutic approach in preclinical prostate cancer models, and currently, neutralizing monoclonal antibody against CCL2 has entered into clinical trials in prostate cancer. In this chapter, targeting CCL2 in prostate cancer will be used as an example to show translation of laboratory findings from cancer molecular biology to the clinic. Copyright © 2010 Elsevier Inc. All rights reserved.

Influence of trade on national CO2 emissions

International Nuclear Information System (INIS)

Munksgaard, Jesper; Pade, Lise-Lotte; Minx, Jan; Lenzen, Manfred

2005-01-01

International trade has an impact on national CO 2 emissions and consequently on the ability to fulfil national CO 2 reduction targets. Through goods and services traded in a globally interdependent world, the consumption in each country is linked to greenhouse gas emissions in other countries. It has been argued that in order to achieve equitable reduction targets, international trade has to be taken into account when assessing nations' responsibility for abating climate change. Especially for open economies such as Denmark, greenhouse gases embodied in internationally traded commodities can have a considerable influence on the national 'greenhouse gas responsibility'. By using input-output modelling, we analyse the influence from international trade on national CO 2 emissions. The aim is to show that trade is the key to define CO 2 responsibility on a macroeconomic level and that imports should be founded in a multi-region model approach. Finally, the paper concludes on the need to consider the impact from foreign trade when negotiating reduction targets and base line scenarios. (Author)

Targeted genomic biomarkers for diagnosis and therapy: from basic research to clinical perspective

International Nuclear Information System (INIS)

Thakur, Mathew L.

2014-01-01

In 2010, more than 30,000 men succumbed to prostate cancer (PC) and more than 240,000 new PC cases were identified in the USA. Digital rectal examination, MRI, and a blood test for prostate specific antigen (PSA) determination play a significant role in detecting advanced PC. However, they are not considered reliable tools for early warning of PC, to detect recurrent cancer or to determine metastatic status of the disease. Unreliable diagnosis results in undertreatment or overtreatment of patients with minimal benefit, enormous morbidity, incontinence, and/or impotence. Histology remains the mainstay of PC confirmation. However, out of >750,000 biopsies performed each year in the USA, >65% show benign pathology, causing patient morbidity and costing hundreds of millions of healthcare dollars. Biological fluids, including urine, represent a promising source of biomarkers for detection and prediction of PC prognosis. Because urine is available non-invasively and readily, numerous studies targeting DNA, RNA, protein and metabolite based biomarkers have been performed. However, none have yet reached the clinic. Even FDA approved PCA3 test has low sensitivity and limitations in predicting aggressive PC

National energy efficiency programme

International Nuclear Information System (INIS)

Anon.

1992-01-01

This paper focusses on energy conservation and specifically on energy efficiency which includes efficiency in the production, delivery and utilisation of energy as part of the total energy system of the economy. A National Energy Efficiency Programme is being launched in the Eighth Plan that will take into account both macro level and policy and planning considerations as well as micro level responses for different category of users in the industry, agriculture, transport and domestic sectors. The need for such a National Energy Efficiency Programme after making an assessment of existing energy conservation activities in the country is discussed. The broad framework and contents of the National Energy Efficiency Programme have been outlined and the Eighth Plan targets for energy conservation and their break-up have been given. These targets, as per the Eighth Plan document are 5000 MW in electricity installed capacity and 6 million tonnes of petroleum products by the terminal year of the Eighth Plan. The issues that need to be examined for each sector for achieving the above targets for energy conservation in the Eighth Plan are discussed briefly. They are: (a) policy and planning, (b) implementation arrangements which include the institutional setup and selective legislation, (c) technological requirements, and (d) resource requirements which include human resources and financial resources. (author)

Headache after traumatic brain injury: a national survey of clinical practices and treatment approaches.

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Brown, Allen W; Watanabe, Thomas K; Hoffman, Jeanne M; Bell, Kathleen R; Lucas, Sylvia; Dikmen, Sureyya

2015-01-01

Individuals with headache after traumatic brain injury (TBI) receive care in a wide variety of clinical locations by physicians trained in multiple specialties. To understand current practice patterns and perceptions of treatment issues among clinicians managing headache after TBI. National survey of current clinical practice using a 20-item questionnaire developed by the authors. Survey respondents were members of the Central Nervous System Council list survey of the American Academy of Physical Medicine and Rehabilitation (N = 1782) and the American Headache Society membership (N = 1260). The survey was sent electronically to potential participants and was followed by 2 biweekly reminders. The survey queried the physicians' clinical setting; their use of headache classification systems, headache diaries, checklists, and diagnostic procedures; the pharmacologic and nonpharmacologic treatments prescribed; and headache chronicity and associated symptoms and disorders among their patients with TBI. Completed surveys were received from 193 respondents. The use of standardized classification systems and checklists was commonly reported. Respondents used nonpharmacologic and pharmacologic treatment approaches with similar frequency and modest perceived success rates. A high frequency of headache-associated new sleep and mood disorders was reported. When response differences occurred between practice settings, they reflected a focus on headache diagnosis, classification, and pharmacologic treatment among neurology and specialty headache clinics, whereas a nonpharmacologic approach to management among TBI specialty and general rehabilitation clinicians was more commonly reported. Management strategies for treating headache after TBI vary widely among general and specialty clinical practices. This suggests that additional research is needed that would lead to an increase in the use of established headache classification and the development of standardized management

Targeting the latest hallmark of cancer: another attempt at 'magic bullet' drugs targeting cancers' metabolic phenotype.

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Cuperlovic-Culf, M; Culf, A S; Touaibia, M; Lefort, N

2012-10-01

The metabolism of tumors is remarkably different from the metabolism of corresponding normal cells and tissues. Metabolic alterations are initiated by oncogenes and are required for malignant transformation, allowing cancer cells to resist some cell death signals while producing energy and fulfilling their biosynthetic needs with limiting resources. The distinct metabolic phenotype of cancers provides an interesting avenue for treatment, potentially with minimal side effects. As many cancers show similar metabolic characteristics, drugs targeting the cancer metabolic phenotype are, perhaps optimistically, expected to be 'magic bullet' treatments. Over the last few years there have been a number of potential drugs developed to specifically target cancer metabolism. Several of these drugs are currently in clinical and preclinical trials. This review outlines examples of drugs developed for different targets of significance to cancer metabolism, with a focus on small molecule leads, chemical biology and clinical results for these drugs.

Variation in radiotherapy target volume definition, dose to organs at risk and clinical target volumes using anatomic (computed tomography) versus combined anatomic and molecular imaging (positron emission tomography/computed tomography): intensity-modulated radiotherapy delivered using a tomotherapy Hi Art machine: final results of the VortigERN study.

Science.gov (United States)

Chatterjee, S; Frew, J; Mott, J; McCallum, H; Stevenson, P; Maxwell, R; Wilsdon, J; Kelly, C G

2012-12-01

Contrast-enhanced computed tomography (CECT) is the current standard for delineating tumours of the head and neck for radiotherapy. Although metabolic imaging with positron emission tomography (PET) has been used in recent years, the studies were non-confirmatory in establishing its routine role in radiotherapy planning in the modern era. This study explored the difference in gross tumour volume and clinical target volume definitions for the primary and nodal volumes when FDG PET/CT was used as compared with CECT in oropharyngeal cancer cases. Twenty patients with oropharyngeal cancers had a PET/CT scan in the treatment position after consent. Target volumes were defined on CECT scans by a consultant clinical oncologist who was blind to the PET scans. After obtaining inputs from a radiologist, another set of target volumes were outlined on the PET/CT data set. The gross and clinical target volumes as defined on the two data sets were then analysed. The hypothesis of more accurate target delineation, preventing geographical miss and comparative overlap volumes between CECT and PET/CT, was explored. The study also analysed the volumes of intersection and analysed whether there was any TNM stage migration when PET/CT was used as compared with CECT for planning. In 17 of 20 patients, the TNM stage was not altered when adding FDG PET information to CT. PET information prevented geographical miss in two patients and identified distant metastases in one case. PET/CT gross tumour volumes were smaller than CECT volumes (mean ± standard deviation: 25.16 cm(3) ± 35.8 versus 36.56 cm(3) ± 44.14; P standard deviation: CECT versus PET/CT 32.48 cm(3) ± 36.63 versus 32.21 cm(3) ± 37.09; P > 0.86) were not statistically different. Similarity and discordance coefficients were calculated and are reported. PET/CT as compared with CECT could provide more clinically relevant information and prevent geographical miss when used for radiotherapy planning for advanced oropharyngeal

Clinical Reasoning Education at US Medical Schools: Results from a National Survey of Internal Medicine Clerkship Directors.

Science.gov (United States)

Rencic, Joseph; Trowbridge, Robert L; Fagan, Mark; Szauter, Karen; Durning, Steven

2017-11-01

Recent reports, including the Institute of Medicine's Improving Diagnosis in Health Care, highlight the pervasiveness and underappreciated harm of diagnostic error, and recommend enhancing health care professional education in diagnostic reasoning. However, little is known about clinical reasoning curricula at US medical schools. To describe clinical reasoning curricula at US medical schools and to determine the attitudes of internal medicine clerkship directors toward teaching of clinical reasoning. Cross-sectional multicenter study. US institutional members of the Clerkship Directors in Internal Medicine (CDIM). Examined responses to a survey that was emailed in May 2015 to CDIM institutional representatives, who reported on their medical school's clinical reasoning curriculum. The response rate was 74% (91/123). Most respondents reported that a structured curriculum in clinical reasoning should be taught in all phases of medical education, including the preclinical years (64/85; 75%), clinical clerkships (76/87; 87%), and the fourth year (75/88; 85%), and that more curricular time should be devoted to the topic. Respondents indicated that most students enter the clerkship with only poor (25/85; 29%) to fair (47/85; 55%) knowledge of key clinical reasoning concepts. Most institutions (52/91; 57%) surveyed lacked sessions dedicated to these topics. Lack of curricular time (59/67, 88%) and faculty expertise in teaching these concepts (53/76, 69%) were identified as barriers. Internal medicine clerkship directors believe that clinical reasoning should be taught throughout the 4 years of medical school, with the greatest emphasis in the clinical years. However, only a minority reported having teaching sessions devoted to clinical reasoning, citing a lack of curricular time and faculty expertise as the largest barriers. Our findings suggest that additional institutional and national resources should be dedicated to developing clinical reasoning curricula to improve

How and when China will exceed its renewable energy deployment targets

International Nuclear Information System (INIS)

Santalco, Aldo

2012-01-01

This paper is focused on the renewable energy targets set by China in its 12th National Development Plan 2011–2015. In particular, the paper examines deployment targets and the means to achieve them, for hydro, wind and solar. These are its priority technologies, in which the country has a level of competitive advantage. For each of these energy sources, four projections have been produced. These projections show whether and when China will meet its deployment targets in terms of the cumulative amount of gigawatts (GW) of installed capacity by 2015. In doing this, historical data from 2005 to 2010 has been analyzed for all three energy sources. Both the average annual growth rate (AAGR), and the compound average growth rate (CAGR) have been computed, in terms of the world averages and China's national performance over this period. AAGR and CAGR have been used for producing four scenarios for each renewable energy, and a logarithmic scale has been applied to them in order to make them more reliable by smoothing out excessive fluctuations. The most likely scenarios for each technology are described. Finally, the gap between these scenarios and the respective national targets set for 2015 and 2020 are calculated. - Highlights: ► The competitive advantages of China for the Renewable Energy Deployment Targets. ► Hydro target met by 2012 with a GW level higher than 31% the target by 2015. ► Wind target met by 2012 with a GW level higher than 35% the target by 2015. ► Solar target met by 2014 with a GW level higher than 23% the target by 2015. ► Best scenarios and gap analysis for 2015 and 2020 targets.

Clinical Trials

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Full Text Available ... and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, ... Center for Health Information Email Alerts Jobs and Careers Site Index About NHLBI National Institute of Health ...

Clinical Trials

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Full Text Available ... and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, ... Customer Service/Center for Health Information Email Alerts Jobs and Careers Site Index About NHLBI National Institute ...

Clinical Trials

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Full Text Available ... whether a new approach causes any harm. In later phases of clinical trials, researchers learn more about ... other National Institutes of Health (NIH) Institutes and Centers sponsor clinical trials. Many other groups, companies, and ...

Clinical Trials

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Full Text Available ... a Clinical Trial If you're interested in learning more about, or taking part in, clinical trials, ... Customer Service/Center for Health Information Email Alerts Jobs and Careers Site Index About NHLBI National Institute ...

Molecular Targets for Targeted Radionuclide Therapy

International Nuclear Information System (INIS)

Mather, S.J.

2009-01-01

radiolabelled regulatory peptides and their metabolically stabilised analogues. Antigen epitopes: Antibodies, as unlabelled biological drugs, are becoming of increasing interest. They exert an antibody-dependent cellular cytotoxicity which leads to lysis of tumour cells. Radiolabelled versions of these (and other) antibodies are being developed worldwide. The disadvantage of the long circulating time of antibodies can be solved by engineering fragments such as diabodies, bivalent single chain variable fragments (scFv), minibodies or by pretargeting approaches. Transmembrane transporters: Other interesting targets are transporters for radiolabelled amino acids and nutrients. Cancer cells require an increased supply of many such nutrients and obtain these by increased expression of some types of amino-acid transporter. A more detailed analysis of the relationship between amino-acid uptake and transporter expression in normal and malignant cells would be very valuable in identifying the clinical therapeutic potential of this class of tracer. Tumour blood supply: Tumours require an efficient blood supply to grow and metastatise and active angiogenesis of new blood vessels is a feature of many tumours. Specific receptors expressed during this process represent a novel class of targets for TRT. Extra-cellular matrix: Recently, another relevant class of target antigens has raised interest. Lectins, or carbohydrate binding proteins, recognize specific oligosaccharide structures on glycoproteins and glycolipids. It is well known that protein and lipid glycosylation are consistently altered in cancer cells for the aberrant activity of specific glycosyltransferase and glycosydases. Experimental evidence demonstrated that tumor growth and progression may depend, at least in part, on the presence of altered glycoproteins on the cell surface, which can mediate aberrant receptor-ligand interactions. (author)

Auto-Targeted Neurostimulation Is Not Superior to Placebo in Chronic Low Back Pain: A Fourfold Blind Randomized Clinical Trial.

Science.gov (United States)

Aguilar Ferrándiz, Maria Encarnación; Nijs, Jo; Gidron, Yori; Roussel, Nathalie; Vanderstraeten, Rob; Van Dyck, Dries; Huysmans, Eva; De Kooning, Margot

2016-07-01

Myofascial trigger points (MTrPs) are common in people with musculoskeletal pain and may play a role in chronic nonspecific low back pain (CLBP). One of the potential treatments of MTrPs is the Nervomatrix Soleve® auto-targeted neurostimulation device, providing targeted transcutaneous electrical nerve stimulation (TENS) to MTrPs in the lower back muscles. To date, no controlled studies have evaluated the effectiveness of this device for the pain management of this population. To examine whether the Nervomatrix Soleve® auto-targeted neurostimulation device is superior over placebo for the treatment of CLBP. A fourfold-blind randomized controlled trial was conducted. Brussels University Hospital, health care centers and pharmacies around Belgium. Participants with CLBP for at least 3 months were randomly assigned to the experimental (the Nervomatrix Soleve® auto-targeted neurostimulation device providing TENS-stimulation and mechanical pressure) or placebo group (the Nervomatrix Soleve® auto-targeted neurostimulation device providing mechanical pressure alone without current). The treatment protocol in both groups consisted of 6 treatment sessions per patient. Participants were evaluated at baseline prior to the intervention, immediately following treatment, and at one month follow-up. Pain and pain behavior (steps climbed) were assessed as primary outcome measures. Secondary outcome measures were pain functioning, health beliefs, symptoms of central sensitization, pain catastrophizing, and kinesiophobia. In total, 39 participants were included in the study. Participants in both groups improved significantly for pain and functioning, but no significant differences were observed between groups. These improvements were not clinically meaningful for any of the reported measures. The health beliefs changed significantly in both groups (P pain, pain behavior, functioning, central sensitization, pain catastrophizing, and health beliefs.

Targets for the APEX experiment at ATLAS

International Nuclear Information System (INIS)

Greene, J.P.; Thomas, G.E.; Leonard, R.H.

1994-01-01

Targets of lead, tantalum, thorium and uranium have been produced for experiments with the APEX (Argonne Positron Experiment) apparatus at ATLAS (Argonne Tandem Linac Accelerator System). APEX is a device built at Argonne National Laboratory to investigate the anomalous positrons observed in collisions of very heavy ion beams on heavy targets. Both fixed and rotating targets have been used. The rotating target system involves a 4-quadrant wheel rotating at speeds up to 700 rpm with the position encoded into the data stream. In addition to the hundreds of targets produced for the heavy-ion reactions studied, a wide variety of targets were employed for beam diagnostics, detector calibration and target wheel development. The experiment used very heavy ion beams ( 238 U, 206 Pb and 208 Pb) from ATLAS and targets of 206 Pb, 208 Pb, 232 Th and 238 U produced in the laboratory

A national survey of pain clinics within the United Kingdom and Ireland focusing on the multidisciplinary team and the incorporation of the extended nursing role.

Science.gov (United States)

Kailainathan, Pungavi; Humble, Stephen; Dawson, Helen; Cameron, Fiona; Gokani, Shyam; Lidder, Gursimren

2018-02-01

Inconsistencies in the availability and quality of pain service provision have been noted nationally, as have lengthy waiting times for appointments and lack of awareness of the Pain Clinic role. The 2013 NHS England report stated that specialist pain services must offer multispecialty and multidisciplinary pain clinics. This national survey of multidisciplinary pain service provision in the United Kingdom and Ireland provides a snapshot of pain service provision in order to review and highlight what variations exist in multidisciplinary team (MDT) provision and working patterns. A common perception among clinicians is that financial pressures have led to alternate ways of staff utilisation with variable degrees of success. The survey included 143 pain clinics, focusing principally on MDT working patterns, MDT composition and adoption of the extended role. The results identified that the majority of Pain Clinics utilise the MDT approach. However, provision of critical components such as regular MDT meetings is highly variable as is the composition of the MDT itself and also working patterns of the individual clinicians. The survey reports the successful use of the extended roles for specialist nurses in follow up clinics. In contrast, the survey highlights that a large proportion of clinicians surveyed have reservations about both the effectiveness and the safety of utilising specialist nurses in the extended role to see new referrals of complex pain patients to pain clinics. This survey underlines the essential requirement for incorporation of greater MDT working locally and nationally and allocation of appropriate resources to facilitate this.

Massively parallel sequencing and targeted exomes in familial kidney disease can diagnose underlying genetic disorders.

Science.gov (United States)

Mallett, Andrew J; McCarthy, Hugh J; Ho, Gladys; Holman, Katherine; Farnsworth, Elizabeth; Patel, Chirag; Fletcher, Jeffery T; Mallawaarachchi, Amali; Quinlan, Catherine; Bennetts, Bruce; Alexander, Stephen I

2017-12-01

Inherited kidney disease encompasses a broad range of disorders, with both multiple genes contributing to specific phenotypes and single gene defects having multiple clinical presentations. Advances in sequencing capacity may allow a genetic diagnosis for familial renal disease, by testing the increasing number of known causative genes. However, there has been limited translation of research findings of causative genes into clinical settings. Here, we report the results of a national accredited diagnostic genetic service for familial renal disease. An expert multidisciplinary team developed a targeted exomic sequencing approach with ten curated multigene panels (207 genes) and variant assessment individualized to the patient's phenotype. A genetic diagnosis (pathogenic genetic variant[s]) was identified in 58 of 135 families referred in two years. The genetic diagnosis rate was similar between families with a pediatric versus adult proband (46% vs 40%), although significant differences were found in certain panels such as atypical hemolytic uremic syndrome (88% vs 17%). High diagnostic rates were found for Alport syndrome (22 of 27) and tubular disorders (8 of 10), whereas the monogenic diagnostic rate for congenital anomalies of the kidney and urinary tract was one of 13. Quality reporting was aided by a strong clinical renal and genetic multidisciplinary committee review. Importantly, for a diagnostic service, few variants of uncertain significance were found with this targeted, phenotype-based approach. Thus, use of targeted massively parallel sequencing approaches in inherited kidney disease has a significant capacity to diagnose the underlying genetic disorder across most renal phenotypes. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

A longitudinal study of organizational formation, innovation adoption, and dissemination activities within the National Drug Abuse Treatment Clinical Trials Network.

Science.gov (United States)

Roman, Paul M; Abraham, Amanda J; Rothrauff, Tanja C; Knudsen, Hannah K

2010-06-01

The National Institute on Drug Abuse established the National Drug Abuse Treatment Clinical Trials Network (CTN) to conduct trials of promising substance abuse treatment interventions in diverse clinical settings and to disseminate results of these trials. This article focuses on three dimensions of CTN's organizational functioning. First, a longitudinal dataset is used to examine CTN's formation as a network of interorganizational interaction among treatment practitioners and researchers. Data indicate strong relationships of interaction and trust, but a decline in problem-centered interorganizational interaction over time. Second, adoption of buprenorphine and motivational incentives among CTN's affiliated community treatment programs (CTPs) is examined over three waves of data. Although adoption is found to increase with CTPs' CTN participation, there is only modest evidence of widespread penetration and implementation. Third, CTPs' pursuit of the CTN's dissemination goals are examined, indicating that such organizational outreach activities are underway and likely to increase innovation diffusion in the future.

IGF system targeted therapy: Therapeutic opportunities for ovarian cancer.

Science.gov (United States)

Liefers-Visser, J A L; Meijering, R A M; Reyners, A K L; van der Zee, A G J; de Jong, S

2017-11-01

The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR) -A and -B. These receptors are activated upon binding to their respective growth factor ligands, IGF-I, IGF-II and insulin, and play an important role in development, maintenance, progression, survival and chemotherapeutic response of ovarian cancer. In many pre-clinical studies anti-IGF-1R/IR targeted strategies proved effective in reducing growth of ovarian cancer models. In addition, anti-IGF-1R targeted strategies potentiated the efficacy of platinum based chemotherapy. Despite the vast amount of encouraging and promising pre-clinical data, anti-IGF-1R/IR targeted strategies lacked efficacy in the clinic. The question is whether targeting the IGF-1R/IR signaling pathway still holds therapeutic potential. In this review we address the complexity of the IGF-1R/IR signaling pathway, including receptor heterodimerization within and outside the IGF system and downstream signaling. Further, we discuss the implications of this complexity on current targeted strategies and indicate therapeutic opportunities for successful targeting of the IGF-1R/IR signaling pathway in ovarian cancer. Multiple-targeted approaches circumventing bidirectional receptor tyrosine kinase (RTK) compensation and prevention of system rewiring are expected to have more therapeutic potential. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

MRO CRISM MAP-PROJECTED TARGETED REDUCED DATA RECORD V1.0

Data.gov (United States)

National Aeronautics and Space Administration — This volume contains the CRISM Map-projected Targeted Reduced Data Record (MTRDR) archive, a collection of multiband image cubes derived from targeted (gimbaled)...

Chemotherapy and molecular target therapy combined with radiation therapy

International Nuclear Information System (INIS)

Akimoto, Tetsuo

2012-01-01

Combined chemotherapy and radiation therapy has been established as standard treatment approach for locally advanced head and neck cancer, esophageal cancer and so on through randomized clinical trials. However, radiation-related morbidity such as acute toxicity also increased as treatment intensity has increased. In underlining mechanism for enhancement of normal tissue reaction in chemo-radiation therapy, chemotherapy enhanced radiosensitivity of normal tissues in addition to cancer cells. Molecular target-based drugs combined with radiation therapy have been expected as promising approach that makes it possible to achieve cancer-specific enhancement of radiosensitivity, and clinical trials using combined modalities have been performed to evaluate the feasibility and efficacy of this approach. In order to obtain maximum radiotherapeutic gain, a detailed understanding of the mechanism underlying the interaction between radiation and Molecular target-based drugs is indispensable. Among molecular target-based drugs, inhibitors targeting epidermal growth factor receptor (EGFR) and its signal transduction pathways have been vigorously investigated, and mechanisms regarding the radiosensitizing effect have been getting clear. In addition, the results of randomized clinical trials demonstrated that radiation therapy combined with cetuximab resulted in improvement of overall and disease-specific survival rate compared with radiation therapy in locally advanced head and neck cancer. In this review, clinical usefulness of chemo-radiation therapy and potential molecular targets for potentiation of radiation-induced cell killing are summarized. (author)

Clinical, Bacteriologic, and Geographic Stratification of Melioidosis Emerges from the Sri Lankan National Surveillance Program.

Science.gov (United States)

Sathkumara, Harindra D; Merritt, Adam J; Corea, Enoka M; Krishnananthasivam, Shivankari; Natesan, Mohan; Inglis, Timothy J J; De Silva, Aruna Dharshan

2018-02-01

Melioidosis, a potentially fatal tropical infection, is said to be underdiagnosed in low-income countries. An increase in melioidosis cases in Sri Lanka allowed us to analyze the relationship among clinical outcome, bacteriology, epidemiology, and geography in the first 108 laboratory-confirmed cases of melioidosis from a nationwide surveillance program. The additional 76 cases of laboratory-confirmed melioidosis confirmed further associations between Burkholderia pseudomallei multilocus sequence typing (MLST) and infection phenotype; ST1137/unifocal bacteremic infection (χ 2 = 3.86, P national genotyping-supported melioidosis registry will improve melioidosis diagnosis, treatment, and prevention where underdiagnosis and mortality rates remain high.

National Ignition Facility subsystem design requirements target positioning subsystem SSDR 1.8.2

International Nuclear Information System (INIS)

Pittenger, L.

1996-01-01

This Subsystem Design Requirement document is a development specification that establishes the performance, design, development and test requirements for the target positioner subsystem (WBS 1.8.2) of the NIF Target Experimental System (WBS 1.8)

Clinical biochemistry education in Spain.

Science.gov (United States)

Queraltó, J M

1994-12-31

Clinical biochemistry in Spain was first established in 1978 as an independent specialty. It is one of several clinical laboratory sciences specialties, together with haematology, microbiology, immunology and general laboratory (Clinical analysis, análisis clinicos). Graduates in Medicine, Pharmacy, Chemistry and Biological Sciences can enter post-graduate training in Clinical Chemistry after a nation-wide examination. Training in an accredited Clinical Chemistry department is 4 years. A national committee for medical and pharmacist specialties advises the government on the number of trainees, program and educational units accreditation criteria. Technical staff includes nurses and specifically trained technologists. Accreditation of laboratories is developed at different regional levels. The Spanish Society for Clinical Biochemistry and Molecular Pathology (SECQ), the national representative in the IFCC, has 1600 members, currently publishes a scientific journal (Química Clinica) and a newsletter. It organizes a continuous education program, a quality control program and an annual Congress.

Transrectal real-time tissue elastography targeted biopsy coupled with peak strain index improves the detection of clinically important prostate cancer.

Science.gov (United States)

Ma, Qi; Yang, Dong-Rong; Xue, Bo-Xin; Wang, Cheng; Chen, Han-Bin; Dong, Yun; Wang, Cai-Shan; Shan, Yu-Xi

2017-07-01

The focus of the present study was to evaluate transrectal real-time tissue elastography (RTE)-targeted two-core biopsy coupled with peak strain index for the detection of prostate cancer (PCa) and to compare this method with 10-core systematic biopsy. A total of 141 patients were enrolled for evaluation. The diagnostic value of peak strain index was assessed using a receiver operating characteristic curve. The cancer detection rates of the two approaches and corresponding positive cores and Gleason score were compared. The cancer detection rate per core in the RTE-targeted biopsy (44%) was higher compared with that in systematic biopsy (30%). The peak strain index value of PCa was higher compared with that of the benign lesion. PCa was detected with the highest sensitivity (87.5%) and specificity (85.5%) using the threshold value of a peak strain index of ≥5.97 with an area under the curve value of 0.95. When the Gleason score was ≥7, RTE-targeted biopsy coupled with peak strain index detected 95.6% of PCa cases, but 84.4% were detected using systematic biopsy. Peak strain index as a quantitative parameter may improve the differentiation of PCa from benign lesions in the prostate peripheral zone. Transrectal RTE-targeted biopsy coupled with peak strain index may enhance the detection of clinically significant PCa, particularly when combined with systematic biopsy.

Ca-48 targets - Home and abroad!

Science.gov (United States)

Greene, John P.; Carpenter, Michael; Janssens, Robert V. F.

2018-05-01

Using the method of reduction/distillation, high-purity films of robust and ductile calcium metal were prepared for use as targets in nuclear physics experiments. These targets, however, are extremely air-sensitive and procedures must be developed for their handling and use without exposure to the air. In most instances, the thin 48Ca target is used on a carrier foil (backing) and a thin covering film of similar material is employed to further reduce re-oxidation. Un-backed metallic targets are rarely produced due to these concerns. In addition, the low natural abundance of the isotope 48Ca provided an increased incentive for the best efficiencies available in their preparation. Here, we describe the preparation of 48Ca targets employing a gold backing and thin gold cover for use at home, Argonne National Laboratory (ANL), as well as abroad, at Osaka University. For the overseas shipments, much care and preparation were necessary to ensure good targets and safe arrival to the experimental facilities.

Laser coupling to reduced-scale targets at Nif Early Light

Energy Technology Data Exchange (ETDEWEB)

Hinkel, D.E.; Schneider, M.B.; Young, B.K.; Holder, J.P.; Langdon, A.B.; Bonanno, G.; Bower, D.E.; Bruns, H.C.; Campbell, K.M.; Celeste, J.R.; Compton, S.; Costa, R.L.; Dewald, E.L.; Dixit, S.N.; Eckart, M.J.; Eder, D.C.; Edwards, M.J.; Ellis, A.D.; Emig, J.A.; Froula, D.H.; Glenzer, S.H.; Hargrove, D.; Haynam, C.A.; Heeter, R.F.; Henesian, M.A.; Holtmeier, G.; James, D.L.; Jancaitis, K.S.; Kalantar, K.H.; Kamperschroer, J.H.; Kauffman, R.L.; Kimbrough, J.; Kirkwood, R.K.; Koniges, A.E.; Landen, O.L.; Landon, M.; Lee, F.D.; MacGowan, B.J.; Mackinnon, A.J.; Manes, K.R.; Marshall, C.; May, M.J.; McDonald, J.W.; Menapace, J.; Moses, S.E.I.; Munro, D.H.; Murray, J.R.; Niemann, C.; Power, G.D.; Rekow, V.; Ruppe, J.A.; Schein, J.; Shepherd, R.; Singh, M.S.; Springer, P.T.; Still, C.H.; Suter, L.J.; Tietbohl, G.L.; Turner, R.E.; VanWonterghem, B.M.; Wallace, R.J.; Warrick, A.; Weber, F.; Wegner, P.J.; Williams, E.A.; Young, P.E. [Lawrence Livermore National Laboratory, Livermore, CA (United States); Baldis, H.A. [California at Davis Univ., CA (United States); Pellinen, D.; Watts, P. [Bechtel Nevada Corporation, Livermore, CA (United States)

2006-06-15

Deposition of maximum laser energy into a small, high-Z enclosure in a short laser pulse creates a hot environment. Such targets were recently included in an experimental campaign using the first four of the 192 beams of the National Ignition Facility (NIF) under construction at the University of California Lawrence Livermore National Laboratory. These targets demonstrate good laser coupling, reaching a radiation temperature of 340 eV. In addition, the Raman backscatter spectrum contains features consistent with Brillouin backscatter of Raman forward scatter. Also, NIF Early Light diagnostics indicate that 20% of the direct backscatter from these reduced-scale targets is in the polarization orthogonal to that of the incident light. (authors)

Development of a national audit tool for juvenile idiopathic arthritis: a BSPAR project funded by the Health Care Quality Improvement Partnership.

Science.gov (United States)

McErlane, Flora; Foster, Helen E; Armitt, Gillian; Bailey, Kathryn; Cobb, Joanna; Davidson, Joyce E; Douglas, Sharon; Fell, Andrew; Friswell, Mark; Pilkington, Clarissa; Strike, Helen; Smith, Nicola; Thomson, Wendy; Cleary, Gavin

2018-01-01

Timely access to holistic multidisciplinary care is the core principle underpinning management of juvenile idiopathic arthritis (JIA). Data collected in national clinical audit programmes fundamentally aim to improve health outcomes of disease, ensuring clinical care is equitable, safe and patient-centred. The aim of this study was to develop a tool for national audit of JIA in the UK. A staged and consultative methodology was used across a broad group of relevant stakeholders to develop a national audit tool, with reference to pre-existing standards of care for JIA. The tool comprises key service delivery quality measures assessed against two aspects of impact, namely disease-related outcome measures and patient/carer reported outcome and experience measures. Eleven service-related quality measures were identified, including those that map to current standards for commissioning of JIA clinical services in the UK. The three-variable Juvenile Arthritis Disease Activity Score and presence/absence of sacro-iliitis in patients with enthesitis-related arthritis were identified as the primary disease-related outcome measures, with presence/absence of uveitis a secondary outcome. Novel patient/carer reported outcomes and patient/carer reported experience measures were developed and face validity confirmed by relevant patient/carer groups. A tool for national audit of JIA has been developed with the aim of benchmarking current clinical practice and setting future standards and targets for improvement. Staged implementation of this national audit tool should facilitate investigation of variability in levels of care and drive quality improvement. This will require engagement from patients and carers, clinical teams and commissioners of JIA services. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Development of a national audit tool for juvenile idiopathic arthritis: a BSPAR project funded by the Health Care Quality Improvement Partnership

Science.gov (United States)

McErlane, Flora; Foster, Helen E; Armitt, Gillian; Bailey, Kathryn; Cobb, Joanna; Davidson, Joyce E; Douglas, Sharon; Fell, Andrew; Friswell, Mark; Pilkington, Clarissa; Strike, Helen; Smith, Nicola; Thomson, Wendy; Cleary, Gavin

2018-01-01

Abstract Objective Timely access to holistic multidisciplinary care is the core principle underpinning management of juvenile idiopathic arthritis (JIA). Data collected in national clinical audit programmes fundamentally aim to improve health outcomes of disease, ensuring clinical care is equitable, safe and patient-centred. The aim of this study was to develop a tool for national audit of JIA in the UK. Methods A staged and consultative methodology was used across a broad group of relevant stakeholders to develop a national audit tool, with reference to pre-existing standards of care for JIA. The tool comprises key service delivery quality measures assessed against two aspects of impact, namely disease-related outcome measures and patient/carer reported outcome and experience measures. Results Eleven service-related quality measures were identified, including those that map to current standards for commissioning of JIA clinical services in the UK. The three-variable Juvenile Arthritis Disease Activity Score and presence/absence of sacro-iliitis in patients with enthesitis-related arthritis were identified as the primary disease-related outcome measures, with presence/absence of uveitis a secondary outcome. Novel patient/carer reported outcomes and patient/carer reported experience measures were developed and face validity confirmed by relevant patient/carer groups. Conclusion A tool for national audit of JIA has been developed with the aim of benchmarking current clinical practice and setting future standards and targets for improvement. Staged implementation of this national audit tool should facilitate investigation of variability in levels of care and drive quality improvement. This will require engagement from patients and carers, clinical teams and commissioners of JIA services. PMID:29069424

Optical alignment techniques for line-imaging velocity interferometry and line-imaging self-emulsion of targets at the National Ignition Facility (NIF)

International Nuclear Information System (INIS)

Malone, Robert M.; Frogget, Brent C.; Kaufman, Morris I.; Tunnell, Thomas W.; Guyton, Robert L.; Reinbachs, Imants P.; Watts, Phillip W.

2007-01-01

The National Ignition Facility (NIF) requires optical diagnostics for measuring shock velocities in shock physics experiments. The Velocity Interferometer System for Any Reflector (VISAR) measures shock velocities, shock breakout times, and emission of 1- to 5-mm targets at a location remote to the NIF target chamber. Three optical systems using the same vacuum chamber port each have a total track of 69 feet. All optical lenses are on kinematic mounts or sliding rails, enabling pointing accuracy of the optical axis to be checked. Counter-propagating laser beams (orange and red) align these diagnostics to a listing of tolerances. The orange alignment laser is introduced at the entrance to the two-level interferometer table and passes forward through the optical systems to the recording streak cameras. The red alignment laser is introduced in front of the recording streak cameras and passes in the reverse direction through all optical elements, out of the interferometer table, eventually reaching the target chamber center. Red laser wavelength is selected to be at the 50 percent reflection point of a special beamsplitter used to separate emission light from the Doppler-shifted interferometer light. Movable aperture cards, placed before and after lens groups, show the spread of alignments spots created by the orange and red alignment lasers. Optical elements include 1- to 15-inch-diameter mirrors, lenses with up to 10.5-inch diameters, beamsplitters, etalons, dove prisms, filters, and pellicles. Alignment of more than 75 optical elements must be verified before each target shot. Archived images from eight alignment cameras prove proper alignment before each shot

Radiotherapy in combination with vascular-targeted therapies

International Nuclear Information System (INIS)

Ciric, Eva; Sersa, Gregor

2010-01-01

Given the critical role of tumor vasculature in tumor development, considerable efforts have been spent on developing therapeutic strategies targeting the tumor vascular network. A variety of agents have been developed, with two general approaches being pursued. Antiangiogenic agents (AAs) aim to interfere with the process of angiogenesis, preventing new tumor blood vessel formation. Vascular-disrupting agents (VDAs) target existing tumor vessels causing tumor ischemia and necrosis. Despite their great therapeutic potential, it has become clear that their greatest clinical utility may lie in combination with conventional anticancer therapies. Radiotherapy is a widely used treatment modality for cancer with its distinct therapeutic challenges. Thus, combining the two approaches seems reasonable. Strong biological rationale exist for combining vascular-targeted therapies with radiation. AAs and VDAs were shown to alter the tumor microenvironment in such a way as to enhance responses to radiation. The results of preclinical and early clinical studies have confirmed the therapeutic potential of this new treatment strategy in the clinical setting. However, concerns about increased normal tissue toxicity, have been raised

Development of a renal transplant clinical pathway: one hospital's journey.

Science.gov (United States)

Darrikhuma, I M

1999-05-01

Mounting pressures to resolve multiple challenges related to quality, cost, and access in a resource-driven, customer-focused health care environment have compelled clinicians to develop innovative strategies to provide cost-effective, state-of-the-art care. Targeted patient groups include those associated with high cost, high volume, or high resource use. Patients undergoing renal transplantation fall into one or more of these categories. Recently, the management of patients with end-stage renal disease (ESRD) has come under national focus, as evidenced by the fact that Health Care Financing Administration (HCFA) has commissioned an ESRD managed care demonstration project. The purpose of this article is to describe how one case management tool--the clinical pathway--can be used to decrease costs and improve outcomes associated with renal transplantation. This discussion will include a review of the origins and components of clinical pathways and a description of how one institution developed, implemented, evaluated, and refined a renal transplantation clinical pathway.

Determining optimal clinical target volume margins in head-and-neck cancer based on microscopic extracapsular extension of metastatic neck nodes

International Nuclear Information System (INIS)

Apisarnthanarax, Smith; Elliott, Danielle D.; El-Naggar, Adel K.; Asper, Joshua A. P.A.; Blanco, Angel; Ang, K. Kian; Garden, Adam S.; Morrison, William H.; Rosenthal, David; Weber, Randal S.; Chao, K.S. Clifford

2006-01-01

Purpose: To determine the optimal clinical target volume margins around the gross nodal tumor volume in head-and-neck cancer by assessing microscopic tumor extension beyond cervical lymph node capsules. Methods and Materials: Histologic sections of 96 dissected cervical lymph nodes with extracapsular extension (ECE) from 48 patients with head-and-neck squamous cell carcinoma were examined. The maximum linear distance from the external capsule border to the farthest extent of the tumor or tumoral reaction was measured. The trends of ECE as a function of the distance from the capsule and lymph node size were analyzed. Results: The median diameter of all lymph nodes was 11.0 mm (range: 3.0-30.0 mm). The mean and median ECE extent was 2.2 mm and 1.6 mm, respectively (range: 0.4-9.0 mm). The ECE was <5 mm from the capsule in 96% of the nodes. As the distance from the capsule increased, the probability of tumor extension declined. No significant difference between the extent of ECE and lymph node size was observed. Conclusion: For N1 nodes that are at high risk for ECE but not grossly infiltrating musculature, 1 cm clinical target volume margins around the nodal gross tumor volume are recommended to cover microscopic nodal extension in head-and-neck cancer

Targeted Nanotechnology for Cancer Imaging

Science.gov (United States)

Toy, Randall; Bauer, Lisa; Hoimes, Christopher; Ghaghada, Ketan B.; Karathanasis, Efstathios

2014-01-01

Targeted nanoparticle imaging agents provide many benefits and new opportunities to facilitate accurate diagnosis of cancer and significantly impact patient outcome. Due to the highly engineerable nature of nanotechnology, targeted nanoparticles exhibit significant advantages including increased contrast sensitivity, binding avidity and targeting specificity. Considering the various nanoparticle designs and their adjustable ability to target a specific site and generate detectable signals, nanoparticles can be optimally designed in terms of biophysical interactions (i.e., intravascular and interstitial transport) and biochemical interactions (i.e., targeting avidity towards cancer-related biomarkers) for site-specific detection of very distinct microenvironments. This review seeks to illustrate that the design of a nanoparticle dictates its in vivo journey and targeting of hard-to-reach cancer sites, facilitating early and accurate diagnosis and interrogation of the most aggressive forms of cancer. We will report various targeted nanoparticles for cancer imaging using X-ray computed tomography, ultrasound, magnetic resonance imaging, nuclear imaging and optical imaging. Finally, to realize the full potential of targeted nanotechnology for cancer imaging, we will describe the challenges and opportunities for the clinical translation and widespread adaptation of targeted nanoparticles imaging agents. PMID:25116445

Molecularly targeted drugs for metastatic colorectal cancer

Directory of Open Access Journals (Sweden)

Cheng YD

2013-11-01

Full Text Available Ying-dong Cheng, Hua Yang, Guo-qing Chen, Zhi-cao Zhang Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China Abstract: The survival rate of patients with metastatic colorectal cancer (mCRC has significantly improved with applications of molecularly targeted drugs, such as bevacizumab, and led to a substantial improvement in the overall survival rate. These drugs are capable of specifically targeting the inherent abnormal pathways in cancer cells, which are potentially less toxic than traditional nonselective chemotherapeutics. In this review, the recent clinical information about molecularly targeted therapy for mCRC is summarized, with specific focus on several of the US Food and Drug Administration-approved molecularly targeted drugs for the treatment of mCRC in the clinic. Progression-free and overall survival in patients with mCRC was improved greatly by the addition of bevacizumab and/or cetuximab to standard chemotherapy, in either first- or second-line treatment. Aflibercept has been used in combination with folinic acid (leucovorin–fluorouracil–irinotecan (FOLFIRI chemotherapy in mCRC patients and among patients with mCRC with wild-type KRAS, the outcomes were significantly improved by panitumumab in combination with folinic acid (leucovorin–fluorouracil–oxaliplatin (FOLFOX or FOLFIRI. Because of the new preliminary studies, it has been recommended that regorafenib be used with FOLFOX or FOLFIRI as first- or second-line treatment of mCRC chemotherapy. In summary, an era of new opportunities has been opened for treatment of mCRC and/or other malignancies, resulting from the discovery of new selective targeting drugs. Keywords: metastatic colorectal cancer (mCRC, antiangiogenic drug, bevacizumab, aflibercept, regorafenib, cetuximab, panitumumab, clinical trial, molecularly targeted therapy

Clinical roles in clinical biochemistry: a national survey of practice in the UK.

Science.gov (United States)

Choudhury, Sirazum M; Williams, Emma L; Barnes, Sophie C; Alaghband-Zadeh, Jamshid; Tan, Tricia M; Cegla, Jaimini

2017-05-01

Background Using an online survey, we collected data to present a picture of how clinical authorization is performed in the UK. Methods A 21-question survey was uploaded to www.surveymonkey.com , and responses were invited via the mail base of the Association for Clinical Biochemistry and Laboratory Medicine. The questionnaire examined the intensity and function of the duty biochemist role and how different types of authorization are used to handle and release results. Results Of 70 responses received, 60 were suitable for analysis. Responses were received from every region of the UK. A typical duty biochemist shift started on average at 8:50, and finished at 17:25. The mean duration was 8 h 58 min. Clinical scientists are the most abundantly represented group on duty biochemist rotas. Higher banded clinical scientists and chemical pathologists covered out-of-hours shifts. Results were handled differently depending on the level of abnormality and the requesting area. Normal results tended to be released either directly from the analyser or after technical then autoauthorization (90%). A greater preference for clinical authorization was seen for abnormal and critical results originating from outpatients (49% and 69%, respectively) or general practice (51% and 71%) than for inpatients (33% and 53%) or A&E (25% and 37%). Conclusions The handling and authorization of biochemistry results varies greatly between laboratories. The role is clearly heterogeneous in the UK. Guidance from the Association for Clinical Biochemistry and Royal College of Pathologists may help to clarify the essential roles of the duty biochemist.

Targeted treatments for cervical cancer: a review

Directory of Open Access Journals (Sweden)

Peralta-Zaragoza O

2012-11-01

Full Text Available Oscar Peralta-Zaragoza,1 Víctor Hugo Bermúdez-Morales,1 Carlos Pérez-Plasencia,2,3 Jonathan Salazar-León,1 Claudia Gómez-Cerón,1 Vicente Madrid-Marina11Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, National Institute of Public Health, Cuernavaca, Morelos, México; 2Oncogenomics Laboratory, National Cancer Institute of Mexico, Tlalpan, México; 3Biomedicine Unit, FES-Iztacala UNAM, México City, MéxicoAbstract: Cervical cancer is the second most common cause of cancer death in women worldwide and the development of new diagnosis, prognostic, and treatment strategies merits special attention. Although surgery and chemoradiotherapy can cure 80%–95% of women with early stage cancer, the recurrent and metastatic disease remains a major cause of cancer death. Many efforts have been made to design new drugs and develop gene therapies to treat cervical cancer. In recent decades, research on treatment strategies has proposed several options, including the role of HPV E6 and E7 oncogenes, which are retained and expressed in most cervical cancers and whose respective oncoproteins are critical to the induction and maintenance of the malignant phenotype. Other efforts have been focused on antitumor immunotherapy strategies. It is known that during the development of cervical cancer, a cascade of abnormal events is induced, including disruption of cellular cycle control, perturbation of antitumor immune response, alteration of gene expression, and deregulation of microRNA expression. Thus, in this review article we discuss potential targets for the treatment of cervical cancer associated with HPV infection, with special attention to immunotherapy approaches, clinical trials, siRNA molecules, and their implications as gene therapy strategies against cervical cancer development.Keywords: Cervical cancer, clinical trials, gene therapy, HPV E6 and E7 oncogenes, siRNAs

Evaluation of a dietary targets monitor.

Science.gov (United States)

Lean, M E J; Anderson, A S; Morrison, C; Currall, J

2003-05-01

To evaluate a two-page food frequency list for use as a Dietary Targets Monitor in large scale surveys to quantify consumptions of the key foods groups targeted in health promotion. Intakes of fruit and vegetables, starchy foods and fish estimated from a validated food frequency questionnaire (FFQ) were compared with a short food frequency list (the Dietary Targets Monitor) specifically designed to assess habitual frequency of consumption of foods in relation to dietary targets which form the basis of a National (Scottish) Food and Health Policy. A total of 1085 adults aged 25-64 y from the Glasgow MONICA Study. : The two questionnaires both collected data on frequencies of food consumption for fruit and vegetables, starchy foods and fish. Comparing the two questionnaires, there were consistent biases, best expressed as ratios (FFQ:Dietary Targets Monitor) between the methods for fruit and vegetables (1.33, 95% CI 1.29, 1.38) and 'starchy foods' (1.08, 95% CI 1.05, 1.12), the DTM showing systematic under-reporting by men. For fish consumption, there was essentially no bias between the methods (0.99, 95% CI 0.94, 1.03). Using calibration factors to adjust for biases, the Dietary Targets Monitor indicated that 16% of the subjects were achieving the Scottish Diet food target (400 g/day) for fruit and vegetable consumption. Nearly one-third (32%) of the subjects were eating the recommended intakes of fish (three portions per week). The Dietary Targets Monitor measure of starchy foods consumption was calibrated using FFQ data to be able to make quantitative estimates: 20% of subjects were eating six or more portions of starchy food daily. A similar estimation of total fat intake and saturated fat intake (g/day) allowed the categorization of subjects as low, moderate or high fat consumers, with broad agreement between the methods. The levels of agreement demonstrated by Bland-Altman analysis, were insufficient to permit use of the adjusted DTM to estimate quantitative

First test of the prompt gamma ray timing method with heterogeneous targets at a clinical proton therapy facility

International Nuclear Information System (INIS)

Hueso-González, Fernando; Enghardt, Wolfgang; Golnik, Christian; Petzoldt, Johannes; Pausch, Guntram; Fiedler, Fine; Priegnitz, Marlen; Römer, Katja E; Wagner, Andreas; Janssens, Guillaume; Prieels, Damien; Smeets, Julien; Vander Stappen, François

2015-01-01

Ion beam therapy promises enhanced tumour coverage compared to conventional radiotherapy, but particle range uncertainties significantly blunt the achievable precision. Experimental tools for range verification in real-time are not yet available in clinical routine. The prompt gamma ray timing method has been recently proposed as an alternative to collimated imaging systems. The detection times of prompt gamma rays encode essential information about the depth-dose profile thanks to the measurable transit time of ions through matter. In a collaboration between OncoRay, Helmholtz-Zentrum Dresden-Rossendorf and IBA, the first test at a clinical proton accelerator (Westdeutsches Protonentherapiezentrum Essen, Germany) with several detectors and phantoms is performed. The robustness of the method against background and stability of the beam bunch time profile is explored, and the bunch time spread is characterized for different proton energies. For a beam spot with a hundred million protons and a single detector, range differences of 5 mm in defined heterogeneous targets are identified by numerical comparison of the spectrum shape. For higher statistics, range shifts down to 2 mm are detectable. A proton bunch monitor, higher detector throughput and quantitative range retrieval are the upcoming steps towards a clinically applicable prototype. In conclusion, the experimental results highlight the prospects of this straightforward verification method at a clinical pencil beam and settle this novel approach as a promising alternative in the field of in vivo dosimetry. (paper)

Clinical trials of CAR-T cells in China.

Science.gov (United States)

Liu, Bingshan; Song, Yongping; Liu, Delong

2017-10-23

Novel immunotherapeutic agents targeting tumor-site microenvironment are revolutionizing cancer therapy. Chimeric antigen receptor (CAR)-engineered T cells are widely studied for cancer immunotherapy. CD19-specific CAR-T cells, tisagenlecleucel, have been recently approved for clinical application. Ongoing clinical trials are testing CAR designs directed at novel targets involved in hematological and solid malignancies. In addition to trials of single-target CAR-T cells, simultaneous and sequential CAR-T cells are being studied for clinical applications. Multi-target CAR-engineered T cells are also entering clinical trials. T cell receptor-engineered CAR-T and universal CAR-T cells represent new frontiers in CAR-T cell development. In this study, we analyzed the characteristics of CAR constructs and registered clinical trials of CAR-T cells in China and provided a quick glimpse of the landscape of CAR-T studies in China.

Off-target Effects in CRISPR/Cas9-mediated Genome Engineering

Directory of Open Access Journals (Sweden)

Xiao-Hui Zhang

2015-01-01

Full Text Available CRISPR/Cas9 is a versatile genome-editing technology that is widely used for studying the functionality of genetic elements, creating genetically modified organisms as well as preclinical research of genetic disorders. However, the high frequency of off-target activity (≥50%—RGEN (RNA-guided endonuclease-induced mutations at sites other than the intended on-target site—is one major concern, especially for therapeutic and clinical applications. Here, we review the basic mechanisms underlying off-target cutting in the CRISPR/Cas9 system, methods for detecting off-target mutations, and strategies for minimizing off-target cleavage. The improvement off-target specificity in the CRISPR/Cas9 system will provide solid genotype–phenotype correlations, and thus enable faithful interpretation of genome-editing data, which will certainly facilitate the basic and clinical application of this technology.

The Appalachian Tri-State Node Experiences with the National Institute on Drug Abuse Clinical Trials Network.

Science.gov (United States)

Kelly, Thomas M; Daley, Dennis C; Byrne, Mimmie; Demarzo, Larry; Smith, Doris; Madl, Stephanie

2011-07-01

The National Institute on Drug Abuse (NIDA)-sponsored Clinical Trial Network (CTN) recently celebrated 10 years of conducting "real world" research into the treatment of addiction. This article reviews the history and results of the most recent CTN studies and describes the experiences of one of the 13 participating research affiliates, the Appalachian Tri-State (ATS) Node. We discuss our "bidirectional" collaboration with multiple community treatment programs (CTPs) on research and dissemination activities and include their experiences as a member of our ATS Node.Results of CTN clinical trials have found unexpectedly that treatment as usual (TAU) is often almost as good as evidence-based interventions such as Motivational Interviewing (MI), possibly due to the difficulty in implementing evidence-based practices most effectively among divergent treatment sites and heterogeneous clinical populations. Some expected findings from the reviewed research are that severity of addiction and comorbidity moderate treatment outcomes and must be accounted for in future CTN-sponsored studies. Notwithstanding these results, much has been learned and recommendations are suggested for changes in CTN research designs that will address methodological limitations and increase treatment effectiveness in future CTN studies.

Assessment of patient safety culture in clinical laboratories in the Spanish National Health System.

Science.gov (United States)

Giménez-Marín, Angeles; Rivas-Ruiz, Francisco; García-Raja, Ana M; Venta-Obaya, Rafael; Fusté-Ventosa, Margarita; Caballé-Martín, Inmaculada; Benítez-Estevez, Alfonso; Quinteiro-García, Ana I; Bedini, José Luis; León-Justel, Antonio; Torra-Puig, Montserrat

2015-01-01

There is increasing awareness of the importance of transforming organisational culture in order to raise safety standards. This paper describes the results obtained from an evaluation of patient safety culture in a sample of clinical laboratories in public hospitals in the Spanish National Health System. A descriptive cross-sectional study was conducted among health workers employed in the clinical laboratories of 27 public hospitals in 2012. The participants were recruited by the heads of service at each of the participating centers. Stratified analyses were performed to assess the mean score, standardized to a base of 100, of the six survey factors, together with the overall patient safety score. 740 completed questionnaires were received (88% of the 840 issued). The highest standardized scores were obtained in Area 1 (individual, social and cultural) with a mean value of 77 (95%CI: 76-78), and the lowest ones, in Area 3 (equipment and resources), with a mean value of 58 (95%CI: 57-59). In all areas, a greater perception of patient safety was reported by the heads of service than by other staff. We present the first multicentre study to evaluate the culture of clinical safety in public hospital laboratories in Spain. The results obtained evidence a culture in which high regard is paid to safety, probably due to the pattern of continuous quality improvement. Nevertheless, much remains to be done, as reflected by the weaknesses detected, which identify areas and strategies for improvement.

Variation of gross tumor volume and clinical target volume definition for lung cancer

International Nuclear Information System (INIS)

Liang Jun; Li Minghui; Chen Dongdu

2011-01-01

Objective: To study the variation of gross tumor volume (GTV) and clinical target volume (CTV) definition for lung cancer between different doctors. Methods: Ten lung cancer patients with PET-CT simulation were selected from January 2008 to December 2009.GTV and CTV of these patients were defined by four professors or associate professors of radiotherapy independently. Results: The mean ratios of largest to smallest GTV and CTV were 1.66 and 1.65, respectively. The mean coefficients of variation for GTV and CTV were 0.20 and 0.17, respectively. System errors of CTV definition in three dimension were less than 5 mm, which was the largest in inferior and superior (0.48 cm, 0.37 cm, 0.32 cm; F=0.40, 0.60, 0.15, P=0.755, 0.618, 0.928). Conclusions: The variation of GTV and CTV definition for lung cancer between different doctors exist. The mean ratios of largest to smallest GTV and CTV were less than 1.7. The variation was in hilar and mediastinum lymphanode regions. System error of CTV definition was the largest (<5 mm) in cranio-caudal direction. (authors)

Heart failure—potential new targets for therapy

Science.gov (United States)

Nabeebaccus, Adam; Zheng, Sean; Shah, Ajay M.

2016-01-01

Abstract Introduction/background Heart failure is a major cause of cardiovascular morbidity and mortality. This review covers current heart failure treatment guidelines, emerging therapies that are undergoing clinical trial, and potential new therapeutic targets arising from basic science advances. Sources of data A non-systematic search of MEDLINE was carried out. International guidelines and relevant reviews were searched for additional articles. Areas of agreement Angiotensin-converting enzyme inhibitors and beta-blockers are first line treatments for chronic heart failure with reduced left ventricular function. Areas of controversy Treatment strategies to improve mortality in heart failure with preserved left ventricular function are unclear. Growing points Many novel therapies are being tested for clinical efficacy in heart failure, including those that target natriuretic peptides and myosin activators. A large number of completely novel targets are also emerging from laboratory-based research. Better understanding of pathophysiological mechanisms driving heart failure in different settings (e.g. hypertension, post-myocardial infarction, metabolic dysfunction) may allow for targeted therapies. Areas timely for developing research Therapeutic targets directed towards modifying the extracellular environment, angiogenesis, cell viability, contractile function and microRNA-based therapies. PMID:27365454

Marketing Plan for the National Security Technology Incubator

Energy Technology Data Exchange (ETDEWEB)

None

2008-03-31

This marketing plan was developed as part of the National Security Preparedness Project by the Arrowhead Center of New Mexico State University. The vision of the National Security Technology Incubator program is to be a successful incubator of technologies and private enterprise that assist the NNSA in meeting new challenges in national safety and security. The plan defines important aspects of developing the incubator, such as defining the target market, marketing goals, and creating strategies to reach the target market while meeting those goals. The three main marketing goals of the incubator are: 1) developing marketing materials for the incubator program; 2) attracting businesses to become incubator participants; and 3) increasing name recognition of the incubator program on a national level.

Detectability counts when assessing populations for biodiversity targets.

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Silviu O Petrovan

Full Text Available Efficient, practical and accurate estimates of population parameters are a necessary basis for effective conservation action to meet biodiversity targets. The brown hare is representative of many European farmland species: historically widespread and abundant but having undergone rapid declines as a result of agricultural intensification. As a priority species in the UK Biodiversity Action Plan, it has national targets for population increase that are part of wider national environmental indicators. Previous research has indicated that brown hare declines have been greatest in pastural landscapes and that gains might be made by focussing conservation effort there. We therefore used hares in pastural landscapes to examine how basic changes in survey methodology can affect the precision of population density estimates and related these to national targets for biodiversity conservation in the UK. Line transects for hares carried out at night resulted in higher numbers of detections, had better-fitting detection functions and provided more robust density estimates with lower effort than those during the day, due primarily to the increased probability of detection of hares at night and the nature of hare responses to the observer. Hare spring densities varied widely within a single region, with a pooled mean of 20.6 hares km(-2, significantly higher than the reported national average of hares in pastures of 3.3 hares km(-2. The high number of encounters allowed us to resolve hare densities at site, season and year scales. We demonstrate how survey conduct can impact on data quantity and quality with implications for setting and monitoring biodiversity targets. Our case study of the brown hare provides evidence that for wildlife species with low detectability, large scale volunteer-based monitoring programmes, either species specific or generalist, might be more successfully and efficiently carried out by a small number of trained personnel able to