A core outcome set for all types of cardiac surgery effectiveness trials: a study protocol for an international eDelphi survey to achieve consensus on what to measure and the subsequent selection of measurement instruments.

PubMed

Moza, A; Benstoem, C; Autschbach, R; Stoppe, C; Goetzenich, A

2015-12-02

Cardiovascular disease (CVD) is a major contributor to the burden of disease and the number one cause of death worldwide. From 1990 until today, more people died from coronary heart disease than from any other cause. CVD is regularly treated with minimally or non-minimally invasive off- or on-pump cardiothoracic surgery and several interventions related to the outcome of the surgical procedures have been evaluated in clinical trials, but heterogeneity in outcome reporting hinders comparison of interventions across trials and limits the ability of research synthesis. This problem is encountered with the introduction of core outcome sets (COSs), which should be measured and reported, as a minimum, in all clinical trials for a specific clinical field. This study protocol describes the methods used to develop a COS for all types of cardiac surgery effectiveness trials. We aim to reach consensus on what to measure in an international three-round eDelphi exercise involving adult patients in need or after cardiothoracic surgery, cardiothoracic surgeons, cardiologists, anaesthesiologists, nursing staff and researchers with expertise in this particular field of medical research. Subsequently, outcome measurement instruments (how to measure) will be determined. Recommendations on COS development given by the Core Outcome Measures in Effectiveness Trials (COMET) Initiative and the Outcome Measures in Rheumatology (OMERACT) Initiative were followed. The proposed COS aims to provide methodological guidance for future cardiothoracic surgical trials to ensure the comparability of effects of interventions across studies and enable research synthesis. This does not imply that primary outcomes should always and exclusively be those of the COS. However, to ensure the comparability of results across trials, the outcomes included in this COS should be considered for inclusion besides measuring trial-specific clinical endpoints.

Bone stimulation for fracture healing: What's all the fuss?

PubMed Central

Victoria, Galkowski; Petrisor, Brad; Drew, Brian; Dick, David

2009-01-01

Approximately 10% of the 7.9 million annual fracture patients in the United States experience nonunion and/or delayed unions, which have a substantial economic and quality of life impact. A variety of devices are being marketed under the name of “bone growth stimulators.” This article provides an overview of electrical and electromagnetic stimulation, ultrasound, and extracorporeal shock waves. More research is needed for knowledge of appropriate device configurations, advancement in the field, and encouragement in the initiation of new trials, particularly large multicenter trials and randomized control trials that have standardized device and protocol methods. PMID:19838359

Laser in Glaucoma and Ocular Hypertension (LiGHT) trial. A multicentre, randomised controlled trial: design and methodology.

PubMed

Gazzard, Gus; Konstantakopoulou, Evgenia; Garway-Heath, David; Barton, Keith; Wormald, Richard; Morris, Stephen; Hunter, Rachael; Rubin, Gary; Buszewicz, Marta; Ambler, Gareth; Bunce, Catey

2018-05-01

The Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial aims to establish whether initial treatment with selective laser trabeculoplasty (SLT) is superior to initial treatment with topical medication for primary open-angle glaucoma (POAG) or ocular hypertension (OHT). The LiGHT Trial is a prospective, unmasked, multicentre, pragmatic, randomised controlled trial. 718 previously untreated patients with POAG or OHT were recruited at six collaborating centres in the UK between 2012 and 2014. The trial comprises two treatment arms: initial SLT followed by conventional medical therapy as required, and medical therapy without laser therapy. Randomisation was provided online by a web-based randomisation service. Participants will be monitored for 3 years, according to routine clinical practice. The target intraocular pressure (IOP) was set at baseline according to an algorithm, based on disease severity and lifetime risk of loss of vision at recruitment, and subsequently adjusted on the basis of IOP control, optic disc and visual field. The primary outcome measure is health-related quality of life (HRQL) (EQ-5D five-level). Secondary outcomes are treatment pathway cost and cost-effectiveness, Glaucoma Utility Index, Glaucoma Symptom Scale, Glaucoma Quality of Life, objective measures of pathway effectiveness, visual function and safety profiles and concordance. A single main analysis will be performed at the end of the trial on an intention-to-treat basis. The LiGHT Trial is a multicentre, pragmatic, randomised clinical trial that will provide valuable data on the relative HRQL, clinical effectiveness and cost-effectiveness of SLT and topical IOP-lowering medication. ISRCTN32038223, Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Use of Ebola Convalescent Plasma to Treat Ebola Virus Disease in Resource-Constrained Settings: A Perspective From the Field

PubMed Central

van Griensven, Johan; De Weiggheleire, Anja; Delamou, Alexandre; Smith, Peter G.; Edwards, Tansy; Vandekerckhove, Philippe; Bah, Elhadj Ibrahima; Colebunders, Robert; Herve, Isola; Lazaygues, Catherine; Haba, Nyankoye; Lynen, Lutgarde

2016-01-01

The clinical evaluation of convalescent plasma (CP) for the treatment of Ebola virus disease (EVD) in the current outbreak, predominantly affecting Guinea, Sierra Leone, and Liberia, was prioritized by the World Health Organization in September 2014. In each of these countries, nonrandomized comparative clinical trials were initiated. The Ebola-Tx trial in Conakry, Guinea, enrolled 102 patients by 7 July 2015; no severe adverse reactions were noted. The Ebola-CP trial in Sierra Leone and the EVD001 trial in Liberia have included few patients. Although no efficacy data are available yet, current field experience supports the safety, acceptability, and feasibility of CP as EVD treatment. Longer-term follow-up as well as data from nontrial settings and evidence on the scalability of the intervention are required. CP sourced from within the outbreak is the most readily available source of anti-EVD antibodies. Until the advent of effective antivirals or monoclonal antibodies, CP merits further evaluation. PMID:26261205

Advances in Retinal Prosthetic Research: A Systematic Review of Engineering and Clinical Characteristics of Current Prosthetic Initiatives.

PubMed

Cheng, Derrick L; Greenberg, Paul B; Borton, David A

2017-03-01

To date, reviews of retinal prostheses have focused primarily on devices undergoing human trials in the Western Hemisphere and fail to capture significant advances in materials and engineering research in countries such as Japan and Korea, as well as projects in early stages of development. To address these gaps, this systematic review examines worldwide advances in retinal prosthetic research, evaluates engineering characteristics and clinical progress of contemporary device initiatives, and identifies potential directions for future research in the field of retinal prosthetics. A literature search using PubMed, Google Scholar, and IEEExplore was conducted following the PRISMA Guidelines for Systematic Review. Inclusion criteria were peer-reviewed papers demonstrating progress in human or animal trials and papers discussing the prosthetic engineering design. For each initiative, a description of the device, its engineering considerations, and recent clinical results were provided. Ten prosthetic initiatives met our inclusion criteria and were organized by stimulation location. Of these initiatives, four have recently completed human trials, three are undergoing multi- or single-center human trials, and three are undergoing preclinical animal testing. Only the Argus II (FDA 2013, CE 2011) has obtained FDA approval for use in the United States; the Alpha-IMS (CE 2013) has achieved the highest visual acuity using a Landolt-C test to date and is the only device presently undergoing a multicenter clinical trial. Several distinct approaches to retinal stimulation have been successful in eliciting visual precepts in animals and/or humans. However, many clinical needs are still not met and engineering challenges must be addressed before a retinal prosthesis with the capability to fully and safely restore functional vision can be realized.

Performance of polymer modified hot mix asphalt pavements : an extended evaluation.

DOT National Transportation Integrated Search

2004-03-01

In the summer of 1996, the Mississippi Department of Transportation (MDOT) initiated a field trial (MDOT : State Study No. 111) and a laboratory study (MDOT State Study No. 123) to evaluate the use of polymer : modified asphalts in hot mix asphalt pa...

Dissecting patterns of preparatory activity in the frontal eye fields during pursuit target selection.

PubMed

Raghavan, Ramanujan T; Joshua, Mati

2017-10-01

We investigated the composition of preparatory activity of frontal eye field (FEF) neurons in monkeys performing a pursuit target selection task. In response to the orthogonal motion of a large and a small reward target, monkeys initiated pursuit biased toward the direction of large reward target motion. FEF neurons exhibited robust preparatory activity preceding movement initiation in this task. Preparatory activity consisted of two components, ramping activity that was constant across target selection conditions, and a flat offset in firing rates that signaled the target selection condition. Ramping activity accounted for 50% of the variance in the preparatory activity and was linked most strongly, on a trial-by-trial basis, to pursuit eye movement latency rather than to its direction or gain. The offset in firing rates that discriminated target selection conditions accounted for 25% of the variance in the preparatory activity and was commensurate with a winner-take-all representation, signaling the direction of large reward target motion rather than a representation that matched the parameters of the upcoming movement. These offer new insights into the role that the frontal eye fields play in target selection and pursuit control. They show that preparatory activity in the FEF signals more strongly when to move rather than where or how to move and suggest that structures outside the FEF augment its contributions to the target selection process. NEW & NOTEWORTHY We used the smooth eye movement pursuit system to link between patterns of preparatory activity in the frontal eye fields and movement during a target selection task. The dominant pattern was a ramping signal that did not discriminate between selection conditions and was linked, on trial-by-trial basis, to movement latency. A weaker pattern was composed of a constant signal that discriminated between selection conditions but was only weakly linked to the movement parameters. Copyright © 2017 the American Physiological Society.

Extending Opportunity: Telidon Technology in Vocational Education.

ERIC Educational Resources Information Center

Turnbull, Amelia Joy

A Mechanics 12 course was chosen by the Alberta Correspondence School for a field trial of computerized delivery systems of vocational education programs to small rural schools where enrollment is low and the construction of vocational laboratories is economically impractical. The Telidon videotex system, which was initially selected, is composed…

DSM-III field trials: I. Initial interrater diagnostic reliability.

PubMed

Spitzer, R L; Forman, J B; Nee, J

1979-06-01

The interrater agreement for major diagnostic categories in studies using DSM-I and DSM-II was usually only fair or poor. In phase one of the DSM-III field trials the overall kappa coefficient of agreement for axis I diagnoses of 281 adult patients was .78 for joint interviews and .66 for diagnoses made after separate interviews; for axis II--personality disorders and specific developmental disorders--the coefficients of agreement were .61 and .54. The interrater reliability of DSM--III is, in general, higher than that previously achieved and may be due to changes in the classification itself, the separation of axis I from axis II conditions, the systematic description of the various disorders, and the inclusion of diagnostic criteria.

Pyrolysis of attapulgite clay blended with yak dung enhances pasture growth and soil health: Characterization and initial field trials.

PubMed

Rafiq, Muhammad Khalid; Joseph, Stephen D; Li, Fei; Bai, Yanfu; Shang, Zhanhuan; Rawal, Aditya; Hook, James M; Munroe, Paul R; Donne, Scott; Taherymoosavi, Sara; Mitchell, David R G; Pace, Ben; Mohammed, Mohanad; Horvat, Joseph; Marjo, Christopher E; Wagner, Avital; Wang, Yanlong; Ye, Jun; Long, Rui-Jun

2017-12-31

Recent studies have shown that the pyrolysis of biomass combined with clay can result in both lower cost and increase in plant yields. One of the major sources of nutrients for pasture growth, as well as fuel and building materials in Tibet is yak dung. This paper reports on the initial field testing in a pasture setting in Tibet using yak dung, biochar, and attapulgite clay/yak dung biochars produced at ratios of 10/90 and 50/50 clay to dung. We found that the treatment with attapulgite clay/yak dung (50/50) biochar resulted in the highest pasture yields and grass nutrition quality. We also measured the properties and yields of mixtures of clay/yak dung biochar used in the field trials produced at 400°C and 500°C to help determine a possible optimum final pyrolysis temperature and dung/clay ratio. It was observed that increasing clay content increased carbon stability, overall biochar yield, pore size, carboxyl and ketone/aldehyde functional groups, hematite and ferrous/ferric sulphate/thiosulphate concentration, surface area and magnetic moment. Decreasing clay content resulted in higher pH, CEC, N content and an enhanced ability to accept and donate electrons. The resulting properties were a complex function of both processing temperature and the percentage of clay for the biochars processed at both 400°C and 500°C. It is possible that the increase in yield and nutrient uptake in the field trial is related to the higher concentration of C/O functional groups, higher surface area and pore volume and higher content of Fe/O/S nanoparticles of multiple oxidation state in the 50/50 clay/dung. These properties have been found to significantly increase the abundance of beneficial microorganisms and hence improve the nutrient cycling and availability in soil. Further field trials are required to determine the optimum pyrolysis production conditions and application rate on the abundance of beneficial microorganisms, yields and nutrient quality. Copyright © 2017 Elsevier B.V. All rights reserved.

Novel strategies in feedforward adaptation to a position-dependent perturbation.

PubMed

Hinder, Mark R; Milner, Theodore E

2005-08-01

To investigate the control mechanisms used in adapting to position-dependent forces, subjects performed 150 horizontal reaching movements over 25 cm in the presence of a position-dependent parabolic force field (PF). The PF acted only over the first 10 cm of the movement. On every fifth trial, a virtual mechanical guide (double wall) constrained subjects to move along a straight-line path between the start and target positions. Its purpose was to register lateral force to track formation of an internal model of the force field, and to look for evidence of possible alternative adaptive strategies. The force field produced a force to the right, which initially caused subjects to deviate in that direction. They reacted by producing deviations to the left, "into" the force field, as early as the second trial. Further adaptation resulted in rapid exponential reduction of kinematic error in the latter portion of the movement, where the greatest perturbation to the handpath was initially observed, whereas there was little modification of the handpath in the region where the PF was active. Significant force directed to counteract the PF was measured on the first guided trial, and was modified during the first half of the learning set. The total force impulse in the region of the PF increased throughout the learning trials, but it always remained less than that produced by the PF. The force profile did not resemble a mirror image of the PF in that it tended to be more trapezoidal than parabolic in shape. As in previous studies of force-field adaptation, we found that changes in muscle activation involved a general increase in the activity of all muscles, which increased arm stiffness, and selectively-greater increases in the activation of muscles which counteracted the PF. With training, activation was exponentially reduced, albeit more slowly than kinematic error. Progressive changes in kinematics and EMG occurred predominantly in the region of the workspace beyond the force field. We suggest that constraints on muscle mechanics limit the ability of the central nervous system to employ an inverse dynamics model to nullify impulse-like forces by generating mirror-image forces. Consequently, subjects adopted a strategy of slightly overcompensating for the first half of the force field, then allowing the force field to push them in the opposite direction. Muscle activity patterns in the region beyond the boundary of the force field were subsequently adjusted because of the relatively-slow response of the second-order mechanics of muscle impedance to the force impulse.

Impact of a clinical trial initiative on clinical trial enrollment in a multidisciplinary prostate cancer clinic.

PubMed

Madsen, Lydia T; Kuban, Deborah A; Choi, Seungtaek; Davis, John W; Kim, Jeri; Lee, Andrew K; Domain, Delora; Levy, Larry; Pisters, Louis L; Pettaway, Curtis A; Ward, John F; Logothetis, Christopher; Hoffman, Karen E

2014-07-01

Clinical oncology trials are hampered by low accrual rates, with fewer than 5% of adult patients with cancer treated on study. Clinical trial enrollment was evaluated at The University of Texas MD Anderson Cancer Center's Multidisciplinary Prostate Cancer Clinic (MPCC) to assess whether a clinical trial initiative, introduced in 2006, impacted enrollment. The trial initiative included posting trial-specific information in clinic, educating patients about appropriate clinical trial options during the treatment recommendation discussion, and providing patients with trial-specific educational information. The investigators evaluated the frequency of clinical trial enrollment for men with newly diagnosed prostate cancer seen in the MPCC from 2004 to 2008. Logistic regression evaluated the impact of patient characteristics and the clinical trial initiative on trial enrollment. The median age of the 1370 men was 64 years; 32% had low-risk, 49% had intermediate-risk, and 19% had high-risk disease. Overall, 74% enrolled in at least one trial and 29% enrolled in more than one trial. Trial enrollment increased from 39% before the initiative (127/326) to 84% (880/1044) after the trial initiative. Patient enrollment increased in laboratory studies (from 25% to 80%), quality-of-life studies (from 10% to 26%), and studies evaluating investigational treatments and systemic agents (from 6% to 15%) after the trial initiative. In multivariate analysis, younger men (P<.001) and men seen after implementation of the clinical trial initiative (P<.001) were more likely to enroll in trials. Clinical trial enrollment in the MPCC was substantially higher than that seen nationally in adult patients with cancer, and enrollment rates increased after the introduction of a clinical trial initiative. Copyright © 2014 by the National Comprehensive Cancer Network.

Standardized Reporting of the Eczema Area and Severity Index (EASI) and the Patient-Oriented Eczema Measure (POEM): A Recommendation by the Harmonising Outcome Measures for Eczema (HOME) Initiative.

PubMed

Grinich, E; Schmitt, J; Küster, D; Spuls, P I; Williams, H C; Chalmers, J R; Thomas, K S; Apfelbacher, C; Prinsen, C A C; Furue, M; Stuart, B; Carter, B; Simpson, E

2018-05-10

Several organizations from multiple fields of medicine are setting standards for clinical research including protocol development, 1 harmonization of outcome reporting, 2 statistical analysis, 3 quality assessment 4 and reporting of findings. 1 Clinical research standardization facilitates the interpretation and synthesis of data, increases the usability of trial results for guideline groups and shared decision-making, and reduces selective outcome reporting bias. The mission of the Harmonising Outcome Measures for Eczema (HOME) initiative is to establish an agreed-upon core set of outcomes to be measured and reported in all clinical trials of atopic dermatitis (AD). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

GPON FTTH trial: lessons learned

NASA Astrophysics Data System (ADS)

Weis, Erik; Hölzl, Rainer; Breuer, Dirk; Lange, Christoph

2009-11-01

This paper reports on a FTTH field trial with GPON (Gigabit-capable passive optical network) technology in the network of Deutsche Telekom in the region of the cities of Berlin and Potsdam. Focus of this trial was to gain practical experience regarding GPON technology, fibre installation in existing ducts with micro duct technology, fibre cabling in customer buildings and impact on operational processes. Furthermore it is reported on an initial Deutsche Telekom FTTB deployment based on GPON technology in the city of Dresden with the main targets to obtain practical deployment and operation experiences with fibre-based access networks and to provide broadband access to a part of the city formerly not servable by DSL (digital subscriber line) technology.

Laser initiation of explosives

NASA Astrophysics Data System (ADS)

Singh, Manpreet; Sethi, V. S.

2002-09-01

Through laser initiation of explosives offers many advantages like controlled threshold energy over wide range, replacement of complicated safety arming mechanisms to simple and better system, immunity to RF/EMI environment etc, but there is greater difficulty to build detonator for all purpose applications and regular field trials. The challenges are to understand the interaction of laser radiation or its induced plasma with explosives, launching and transmission of high power laser beam, coupling and focussing to desired target area. This paper looks into the details of those facts.

Securing Mobile Networks in an Operational Setting

NASA Technical Reports Server (NTRS)

Ivancic, William D.; Stewart, David H.; Bell, Terry L.; Paulsen, Phillip E.; Shell, Dan

2004-01-01

This paper describes a network demonstration and three month field trial of mobile networking using mobile-IPv4. The network was implemented as part of the US Coast Guard operational network which is a ".mil" network and requires stringent levels of security. The initial demonstrations took place in November 2002 and a three month field trial took place from July through September of 2003. The mobile network utilized encryptors capable of NSA-approved Type 1 algorithms, mobile router from Cisco Systems and 802.11 and satellite wireless links. This paper also describes a conceptual architecture for wide-scale deployment of secure mobile networking in operational environments where both private and public infrastructure is used. Additional issues presented include link costs, placement of encryptors and running routing protocols over layer-3 encryption devices.

Point-Source and Area-Wide Field Studies of Pyriproxyfen Autodissemination Against Urban Container-Inhabiting Mosquitoes

DTIC Science & Technology

2014-04-05

trials by Itoh (1994) and subsequently confirmed by Chism and Apperson (2003), Devine et al. (2009) demonstrated in field experiments in Peru that...105 ha in area (Fig. 2), whereas, the control site was in Union Beach , NJ (40.2650 lat., - 74.71026 long.) and spanned 181 ha. Both the treatment and...people/km2) than Union Beach (1384.7 people/km2). We initially intended to assess pyriproxyfen-based area-wide autodissemination by treating 25% of an

Comparison of methods to detect Pasteurella multocida in carrier waterfowl

USGS Publications Warehouse

Samuel, M.D.; Shadduck, D.J.; Goldberg, Diana R.; Johnson, W.P.

2003-01-01

We conducted laboratory challenge trials using mallard ducks (Anas platyrhynchos) to compare methods for detecting carriers of Pasteurella multocida, the bacterium that causes avian cholera, in wild birds. Birds that survived the initial infection were euthanized at 2-4 wk intervals up to 14 wk post challenge. Isolates of P. multocida were obtained at necropsy from 23% of the birds that survived initial infection. We found that swab samples (oral, cloacal, nasal, eye, and leg joint) were most effective for detecting carrier birds up to 14 wk post infection. No detectable differences in isolation were observed for samples stored in either 10% dimethysulfoxide or brain heart infusion broth. The frequency of detecting carriers in our challenge trials appeared to be related to mortality rates observed during the trial, but was not related to a number of other factors including time after challenge, time delays in collecting tissues postmortem, and route of infection. In our trials, there was little association between antibody levels and carrier status. We concluded that swabs samples collected from recently dead birds, stored in liquid nitrogen, and processed using selective broth provide a feasible field method for detecting P. multocida carriers in wild waterfowl.

A decade of the Clinical Trials Transformation Initiative: What have we accomplished? What have we learned?

PubMed

Tenaerts, P; Madre, L; Landray, M

2018-02-01

The Clinical Trials Transformation Initiative reflects on 10 years of working to improve the quality and efficiency of clinical trials. This article highlights many of the Clinical Trials Transformation Initiative's accomplishments and offers examples of the impact that the Clinical Trials Transformation Initiative has had on the clinical trials enterprise. After conducting more than 25 projects and issuing recommendations for specific strategies to improve the design and execution of clinical trials, some common themes and lessons learned have emerged. Lessons include the importance of engaging many stakeholders, advanced planning to address critical issues, discontinuation of non-value added practices, and new opportunities presented by technology. Through its work, the Clinical Trials Transformation Initiative has also derived some operational best practices for conducting collaborative, multi-stakeholder projects covering project selection, project team dynamics and execution, and multi-stakeholder meetings and team discussions. Through these initiatives, the Clinical Trials Transformation Initiative has helped move the needle toward needed change in the clinical trials enterprise that has directly impacted stakeholders and patients alike.

Canadian aeronautical mobile data trials

NASA Technical Reports Server (NTRS)

Pedersen, Allister; Pearson, Andrea

1993-01-01

This paper describes a series of aeronautical mobile data trials conducted on small aircraft (helicopters and fixed wing) utilizing a low-speed store-and-forward mobile data service. The paper outlines the user requirements for aeronautical mobile satellite communications. 'Flight following' and improved wide-area dispatch communications were identified as high priority requirements. A 'proof-of-concept' trial in a Cessna Skymaster aircraft is described. This trial identified certain development work as essential to the introduction of commercial service including antenna development, power supply modifications and doppler software modifications. Other improvements were also proposed. The initial aeronautical mobile data service available for pre-operational (Beta) trials is outlined. Pre-operational field trials commenced in October 1992 and consisted of installations on a Gralen Communications Inc. Cessna 177 and an Aerospatiale Astar 350 series light single engine helicopter. The paper concludes with a discussion of desirable near term mobile data service developments, commercial benefits, current safety benefits and potential future applications for improved safety.

Ten-year growth comparison between rooted cuttings and seedlings of loblolly pine

Treesearch

H.E. Stelzer; G. Sam Foster; D.V. Shaw; J.B. McRae

1997-01-01

Rooted cuttings and seedlings of loblolly pine (Pinus taeda L.) were established in a central Alabama field trial. Five, full-sib families, with an average number of six clones per family, were evaluated. Mean cutting/seedling height ratios revealed that despite initial differences in size, relative growth rates of both propagule types stabilized and...

DIZZYNET--a European network initiative for vertigo and balance research: visions and aims.

PubMed

Zwergal, Andreas; Brandt, Thomas; Magnusson, Mans; Kennard, Christopher

2016-04-01

Vertigo is one of the most common complaints in medicine. Despite its high prevalence, patients with vertigo often receive either inappropriate or inadequate treatment. The most important reasons for this deplorable situation are insufficient interdisciplinary cooperation, nonexistent standards in diagnostics and therapy, the relatively rare translations of basic science findings to clinical applications, and the scarcity of prospective controlled multicenter clinical trials. To overcome these problems, the German Center for Vertigo and Balance Disorders (DSGZ) started an initiative to establish a European Network for Vertigo and Balance Research called DIZZYNET. The central aim is to create a platform for collaboration and exchange among scientists, physicians, technicians, and physiotherapists in the fields of basic and translational research, clinical management, clinical trials, rehabilitation, and epidemiology. The network will also promote public awareness and help establish educational standards in the field. The DIZZYNET has the following objectives as regards structure and content: to focus on multidisciplinary translational research in vertigo and balance disorders, to develop interdisciplinary longitudinal and transversal networks for patient care by standardizing and personalizing the management of patients, to increase methodological competence by implementing common standards of practice and quality management, to internationalize the infrastructure for prospective multicenter clinical trials, to increase recruitment capacity for clinical trials, to create a common data base for patients with vertigo and balance disorders, to offer and promote attractive educational and career paths in a network of cooperating institutions. In the long term, the DIZZYNET should serve as an internationally visible network for interdisciplinary and multiprofessional research on vertigo and balance disorders. It ideally should equally attract the afflicted patients and those managing their disorders. DIZZYNET will not compete with the traditional national or international societies active in the field, but will function as an additional structure that addresses some of the above problems.

Can we improve the performance and reporting of investigator-initiated clinical trials? Rheumatoid arthritis as an example.

PubMed

Landewé, Robert B M; Smolen, Josef S; Weinblatt, Michael E; Emery, Paul; Dougados, Maxime; Fleischmann, Roy; Aletaha, Daniel; Kavanaugh, Arthur; van der Heijde, Désirée

2014-10-01

Investigator-initiated trials, some of which have been referred to as comparative effectiveness trials, pragmatic trials, or strategy trials, are sometimes considered to be of greater clinical importance than industry-driven trials, because they address important but unresolved clinical questions that differ from the questions asked in industry-driven trials. Regulatory authorities have provided methodological guidance for industry-driven trials for the approval of new treatments, but such guidance is less clear for investigator-initiated trials. The European League Against Rheumatism (EULAR) task force for the update of the recommendations for the management of rheumatoid arthritis has critically looked at the methodological quality and conduct of many investigator-initiated trials, and has identified a number of concerns. In this Viewpoint paper, we highlight commonly encountered issues that are discussed using examples of well-known investigator-initiated trials. These issues cover three themes: (1) design choice (superiority vs non-inferiority designs); (2) statistical power and (3) convenience reporting. Since we acknowledge the importance of investigator-initiated research, we also propose a shortlist of points-to-consider when designing, performing and reporting investigator-initiated trials. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Post-trial apomorphine at an autoreceptor dose level can eliminate apomorphine conditioning and sensitization: support for the critical role of dopamine in re-consolidation.

PubMed

Carrera, Marinete Pinheiro; Carey, Robert J; Cruz Dias, Flávia Regina; dos Santos Sampaio, Maria de Fátima; de Matos, Liana Wermelinger

2013-01-01

Re-exposure to conditioned drug stimuli triggers re-consolidation processes. In the present study post-trial apomorphine treatments were administered in order to interact with the re-consolidation of an apomorphine conditioned/sensitized locomotor response. A low (0.05 mg/kg) and a high (2.0mg/kg) dose were used to inhibit or to enhance dopamine activity, respectively. Initially, groups received 5 daily apomorphine (2.0mg/kg)/vehicle treatments either paired or unpaired to open-field placement. The paired treatments generated a progressive locomotor response. Subsequently, all groups received a 5 min non-drug test for conditioning and a conditioned locomotor response was observed in the paired group. The groups received another apomorphine (2.0mg/kg)/vehicle treatment as a re-induction treatment. At this stage the post-trial protocol was initiated. One set of paired, unpaired and vehicle groups were given a low dose of apomorphine (0.05 mg/kg) post-trial; another set received a high dose of apomorphine (2.0mg/kg) post-trial. The remaining group set received vehicle post-trial. The low dose post-trial treatment eliminated the conditioned and sensitized locomotor response and the high dose post-trial treatment enhanced the conditioned and sensitized locomotor response. The efficacy of the post-trial apomorphine treatments to modify the conditioned and the sensitized response after a brief non-drug exposure to test cues supports the proposition that exteroceptive cues control conditioning and sensitization and that the interoceptive drug cues make little or no associational contribution to apomorphine conditioning and sensitization. In addition, the findings point to the importance of dopamine activation in both the acquisition and re-consolidation of conditioning processes. Copyright © 2012 Elsevier B.V. All rights reserved.

DSM-III field trials: II. Initial experience with the multiaxial system.

PubMed

Spitzer, R L; Forman, J B

1979-06-01

The multiaxial system of DSM-III includes nondiagnostic data that are valuable in understanding possible etiological factors and in treatment planning and prognosis. The authors describe the reliability of axis IV--severity of psychosocial stressors--and axis V--highest level of adaptive functioning in the past year--for 281 adult patients interviewed in phase one of the DSM-III field trials. The kappa coefficient of agreement for axis IV was .62 for joint interviews and .58 for separate interviews, which the authors consider at least fair. Reliability for axis V was quite good, .80 for joint interviews and .69 for separate interviews. Eighty-one percent of the participating clinicians judged the multiaxial system to be a useful addition to traditional diagnostic evaluation, although many indicated that they had difficulty quantifying severity of psychosocial stressors.

Determining the influence of rainfall patterns and carbendazim on the surface activity of the earthworm Lumbricus terrestris.

PubMed

Ellis, Sian R; Hodson, Mark E; Wege, Phil

2010-08-01

Carbendazim is highly toxic to earthworms and is used as a standard control substance when running field-based trials of pesticides, but results using carbendazim are highly variable. In the present study, impacts of timing of rainfall events following carbendazim application on earthworms were investigated. Lumbricus terrestris were maintained in soil columns to which carbendazim and then deionized water (a rainfall substitute) were applied. Carbendazim was applied at 4 kg/ha, the rate recommended in pesticide field trials. Three rainfall regimes were investigated: initial and delayed heavy rainfall 24 h and 6 d after carbendazim application, and frequent rainfall every 48 h. Earthworm mortality and movement of carbendazim through the soil was assessed 14 d after carbendazim application. No detectable movement of carbendazim occurred through the soil in any of the treatments or controls. Mortality in the initial heavy and frequent rainfall was significantly higher (approximately 55%) than in the delayed rainfall treatment (approximately 25%). This was due to reduced bioavailability of carbendazim in the latter treatment due to a prolonged period of sorption of carbendazim to soil particles before rainfall events. The impact of carbendazim application on earthworm surface activity was assessed using video cameras. Carbendazim applications significantly reduced surface activity due to avoidance behavior of the earthworms. Surface activity reductions were least in the delayed rainfall treatment due to the reduced bioavailability of the carbendazim. The nature of rainfall events' impacts on the response of earthworms to carbendazim applications, and details of rainfall events preceding and following applications during field trials should be made at a higher level of resolution than is currently practiced according to standard International Organization for Standardization protocols. Copyright 2010 SETAC

The Depression Inventory Development Workgroup: A Collaborative, Empirically Driven Initiative to Develop a New Assessment Tool for Major Depressive Disorder.

PubMed

Vaccarino, Anthony L; Evans, Kenneth R; Kalali, Amir H; Kennedy, Sidney H; Engelhardt, Nina; Frey, Benicio N; Greist, John H; Kobak, Kenneth A; Lam, Raymond W; MacQueen, Glenda; Milev, Roumen; Placenza, Franca M; Ravindran, Arun V; Sheehan, David V; Sills, Terrence; Williams, Janet B W

2016-01-01

The Depression Inventory Development project is an initiative of the International Society for CNS Drug Development whose goal is to develop a comprehensive and psychometrically sound measurement tool to be utilized as a primary endpoint in clinical trials for major depressive disorder. Using an iterative process between field testing and psychometric analysis and drawing upon expertise of international researchers in depression, the Depression Inventory Development team has established an empirically driven and collaborative protocol for the creation of items to assess symptoms in major depressive disorder. Depression-relevant symptom clusters were identified based on expert clinical and patient input. In addition, as an aid for symptom identification and item construction, the psychometric properties of existing clinical scales (assessing depression and related indications) were evaluated using blinded datasets from pharmaceutical antidepressant drug trials. A series of field tests in patients with major depressive disorder provided the team with data to inform the iterative process of scale development. We report here an overview of the Depression Inventory Development initiative, including results of the third iteration of items assessing symptoms related to anhedonia, cognition, fatigue, general malaise, motivation, anxiety, negative thinking, pain and appetite. The strategies adopted from the Depression Inventory Development program, as an empirically driven and collaborative process for scale development, have provided the foundation to develop and validate measurement tools in other therapeutic areas as well.

It's plain and simple: transparency is good for science and in the public interest.

PubMed

Denegri, Simon; Faure, Helene

2013-07-12

In the past couple of years, there has been a growing focus on the need to make scientific output accessible to a greater number of people, especially in the field of clinical research. The public are being urged to become more well-informed and to ask their doctors about taking part in clinical trials. A key finding of a report from the Association of Medical Research Charities was that all published scientific papers would benefit from having a section in plain English. Researchers running a clinical trial are expected to provide a summary of their intended research at various stages of the research process. However, there is evidence that existing summaries are of variable length and quality and not always in plain English. As a result, the National Institute for Health Research (NIHR) commissioned a review of the guidance that is available to researchers. However, recent initiatives demonstrate that there are still a number of challenges in making current research both accessible and understandable by prospective participants. BioMed Central also has a number of ongoing initiatives involving trial registration services and journals.

Restoration of chestnuts as a timber crop in Connecticut

Treesearch

S.L. Anagnostakis; C.C. Pinchot

2014-01-01

American chestnut trees were an important source of timber in Connecticut until chestnut blight disease reduced them to understory shrubs. Breeding begun in 1930 has now produced trees with enough resistance to initiate field trials in the forest. Biological control by hypovirulence viruses is being used in the plots in an effort to keep native trees alive. If native...

Educational Technology Program. Quarterly Technical Summary Report, 1 December 1971-29 February 1972.

ERIC Educational Resources Information Center

Frick, Frederick C.

The Lincoln Training System (LTS-3) is a computer-assisted instructional system for training Air Traffic Controllers and Basic Electronic students in the United States Air Force. This document describes the components of the system prior to its initial field trial in mid-April 1972 at Kessler Air Force Base. The system is made up of 14 Basic…

An Initial Field Trial of an Instrument for Measuring Learning Strategies of Middle School Students. Research Report. ETS RR-08-03

ERIC Educational Resources Information Center

Liu, Ou Lydia; Jackson, Teresa; Ling, Guangming

2008-01-01

Learning strategies have been increasingly recognized as a useful tool to promote effective learning. In response to the lack of available learning strategies measures for middle school students, this study designed an instrument for these students, assessing behavioral, cognitive, and metacognitive strategies. This instrument, the Middle School…

Toward multidomain integrated network management for ATM and SDH networks

NASA Astrophysics Data System (ADS)

Galis, Alex; Gantenbein, Dieter; Covaci, Stefan; Bianza, Carlo; Karayannis, Fotis; Mykoniatis, George

1996-12-01

ACTS Project AC080 MISA has embarked upon the task of realizing and validating via European field trials integrated end-to-end management of hybrid SDH and ATM networks in the framework of open network provision. This paper reflects the initial work of the project and gives an overview of the proposed MISA system architecture and initial design. We describe our understanding of the underlying enterprise model in the network management context, including the concept of the MISA Global Broadband Connectivity Management service. It supports Integrated Broadband Communication by defining an end-to-end broadband connection service in a multi-domain business environment. Its implementation by the MISA consortium within trials across Europe aims for an efficient management of network resources of the SDH and ATM infrastructure, considering optimum end-to-end quality of service and the needs of a number of telecommunication actors: customers, value-added service providers, and network providers.

Comparative field trial of alternative vector control strategies for non-domiciliated Triatoma dimidiata.

PubMed

Ferral, Jhibran; Chavez-Nuñez, Leysi; Euan-Garcia, Maria; Ramirez-Sierra, Maria Jesus; Najera-Vazquez, M Rosario; Dumonteil, Eric

2010-01-01

Chagas disease is a major vector-borne disease, and regional initiatives based on insecticide spraying have successfully controlled domiciliated vectors in many regions. Non-domiciliated vectors remain responsible for a significant transmission risk, and their control is a challenge. We performed a proof-of-concept field trial to test alternative strategies in rural Yucatan, Mexico. Follow-up of house infestation for two seasons following the interventions confirmed that insecticide spraying should be performed annually for the effective control of Triatoma dimidiata; however, it also confirmed that insect screens or long-lasting impregnated curtains may represent good alternative strategies for the sustained control of these vectors. Ecosystemic peridomicile management would be an excellent complementary strategy to improve the cost-effectiveness of interventions. Because these strategies would also be effective against other vector-borne diseases, such as malaria or dengue, they could be integrated within a multi-disease control program.

Fixation of Radiological Contamination; International Collaborative Development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rick Demmer

2013-03-01

A cooperative international project was conducted by the Idaho National Laboratory (INL) and the United Kingdom’s National Nuclear Laboratory (NNL) to integrate a capture coating with a high performance atomizing process. The initial results were promising, and lead to further trials. The somewhat longer testing and optimization process has resulted in a product that could be demonstrated in the field to reduce airborne radiological dust and contamination.

Involved-node radiotherapy in early-stage Hodgkin's lymphoma. Definition and guidelines of the German Hodgkin Study Group (GHSG).

PubMed

Eich, Hans Theodor; Müller, Rolf-Peter; Engenhart-Cabillic, Rita; Lukas, Peter; Schmidberger, Heinz; Staar, Susanne; Willich, Normann

2008-08-01

Radiotherapy of Hodgkin's Lymphoma has evolved from extended-field to involved-field (IF) radiotherapy reducing toxicity whilst maintaining high cure rates. Recent publications recommend further reduction in the radiation field to involved-node (IN) radiotherapy; however, this concept has never been tested in a randomized trial. The German Hodgkin Study Group aims to compare it with standard IF radiotherapy in their future HD17 trial. ALL patients must be examined by the radiation oncologist before the start of chemotherapy. At that time, patients must have complete staging CT scans. For patients with IN radiotherapy, a radiation planning CT before and after chemotherapy with patients in the treatment position is recommended. Fusion techniques, allowing the overlapping of the pre- and postchemotherapy CT scans, should be used. Usage of PET-CT scans with patients in the treatment position is recommended, whenever possible. The clinical target volume encompasses the initial volume of the Lymph node(s) before chemotherapy and incorporates the initial Location and extent of the disease taking the displacement of the normal tissues into account. The margin of the planning target volume should be 2 cm in axial and 3 cm in craniocaudal direction. If necessary, it can be reduced to 1-1.5 cm. To minimize Lung and cardiac toxicity, the target definition in the mediastinum is different. The concept of IN radiotherapy has been proposed as a means to further improve the therapeutic ratio by reducing the risk of radiation-induced toxicity, including second malignancies. Field sizes wiLL further decrease compared to IF radiotherapy.

Development and feasibility of the misuse, abuse, and diversion drug event reporting system (MADDERS®).

PubMed

Treister, Roi; Trudeau, Jeremiah J; Van Inwegen, Richard; Jones, Judith K; Katz, Nathaniel P

2016-12-01

Inappropriate use of analgesic drugs has become increasingly pervasive over the past decade. Currently, drug abuse potential is primarily assessed post-marketing; no validated tools are available to assess this potential in phase II and III clinical trials. This paper describes the development and feasibility testing of a Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS), which aims to identify potentially abuse-related events and classify them according to a recently developed classification scheme, allowing the quantification of these events in clinical trials. The system was initially conceived and designed with input from experts and patients, followed by field-testing to assess its feasibility and content validity in both completed and ongoing clinical trials. The results suggest that MADDERS is a feasible system with initial validity. It showed higher rates of the triggering events in subjects taking medications with known abuse potential than in patients taking medications without abuse potential. Additionally, experts agreed on the classification of most abuse-related events in MADDERS. MADDERS is a new systematic approach to collect information on potentially abuse-related events in clinical trials and classify them. The system has demonstrated feasibility for implementation. Additional research is ongoing to further evaluate its validity. Currently, there are no validated tools to assess drug abuse potential during clinical trials. Because of its ease of implementation, its systematic approach, and its preliminary validation results, MADDERS could provide such a tool for clinical trials. (Am J Addict 2016;25:641-651). © 2016 American Academy of Addiction Psychiatry.

Adaptive designs in clinical trials.

PubMed

Bowalekar, Suresh

2011-01-01

In addition to the expensive and lengthy process of developing a new medicine, the attrition rate in clinical research was on the rise, resulting in stagnation in the development of new compounds. As a consequence to this, the US Food and Drug Administration released a critical path initiative document in 2004, highlighting the need for developing innovative trial designs. One of the innovations suggested the use of adaptive designs for clinical trials. Thus, post critical path initiative, there is a growing interest in using adaptive designs for the development of pharmaceutical products. Adaptive designs are expected to have great potential to reduce the number of patients and duration of trial and to have relatively less exposure to new drug. Adaptive designs are not new in the sense that the task of interim analysis (IA)/review of the accumulated data used in adaptive designs existed in the past too. However, such reviews/analyses of accumulated data were not necessarily planned at the stage of planning clinical trial and the methods used were not necessarily compliant with clinical trial process. The Bayesian approach commonly used in adaptive designs was developed by Thomas Bayes in the 18th century, about hundred years prior to the development of modern statistical methods by the father of modern statistics, Sir Ronald A. Fisher, but the complexity involved in Bayesian approach prevented its use in real life practice. The advances in the field of computer and information technology over the last three to four decades has changed the scenario and the Bayesian techniques are being used in adaptive designs in addition to other sequential methods used in IA. This paper attempts to describe the various adaptive designs in clinical trial and views of stakeholders about feasibility of using them, without going into mathematical complexities.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leong, JoAnn Ching

A recombinant DNA vaccine to IHNV was prepared and tested in field trials at Clear Springs Trout Company's Box Canyon Hatchery in Buhl, Idaho this year in Phase III of the project. The vaccine under consideration in these field trials consisted of lysed bacteria that contained a plasmid which expressed an antigenic portion of the IHNV glycoprotein. In addition, laboratory trials with a bacterial expressed viral nucleoprotein indicated that this served as an immune adjuvant. Therefore, a decision was made to conduct these field trials on a vaccine containing both IHNV glycoprotein and IHNV nucleoprotein. Original plans to conduct themore » field trial at Dworshak National Fish Hatchery were canceled because a management decision was made by Dworshak Fish and Wildlife personnel to rear steelhead salmon eggs from IHNV positive parents at Kooskia National Fish Hatchery. This decision, which was made without prior notification to us, resulted in some discussion at the IHNV committee meeting convened by the Fish and Wildlife Service in Moscow, Idaho on April 27, 1989. At that time, the authors dismay at this decision was voiced and the prediction that an outbreak of IHNV would occur at Kooskia was made. In less than a week, a massive IHNV outbreak did occur at Kooskia and plans to run a field trial at this facility had to be discarded. An alternative site was found at the Box Canyon Hatchery site of Clear Springs Trout Company. Dr. Robert Busch, Director of Research and Development for Clear Springs Trout Company, offered the use of the site. In preparation for the site change they consulted Mary Buckman, Oregon Department of Fish and Wildlife statistician, and they obtained a sample of the IHN virus present at Box Canyon. The Box Canyon virus isolate was typed by reactivity with monoclonal antibodies by Dr. Sandra Ristow at Washington State University. There was insufficient time to examine the vaccine efficacy with the Box Canyon virus isolate in laboratory trials and they had to prepare for field trials without this supporting data. In addition, they had to make numerous changes in the vaccination schedule and in the design of the challenge to accommodate the new site. Most importantly, an application for a change in site had to be approved by the Idaho State Veterinarian and the Veterinary Biologics Group at the USDA National Office in Hyattsville, Maryland. A new work plan was formulated, approvals were obtained, the demands for statistical analyses were satisfied in the new work plan, and 20,000 rainbow trout fry were vaccinated on July 19, 1989. The following is a summary of the results of the work that was initiated at Box Canyon Hatchery.« less

Pulsed Electromagnetic Fields in the treatment of fresh scaphoid fractures. A multicenter, prospective, double blind, placebo controlled, randomized trial

PubMed Central

2011-01-01

Background The scaphoid bone is the most commonly fractured of the carpal bones. In the Netherlands 90% of all carpal fractures is a fracture of the scaphoid bone. The scaphoid has an essential role in functionality of the wrist, acting as a pivot. Complications in healing can result in poor functional outcome. The scaphoid fracture is a troublesome fracture and failure of treatment can result in avascular necrosis (up to 40%), non-union (5-21%) and early osteo-arthritis (up to 32%) which may seriously impair wrist function. Impaired consolidation of scaphoid fractures results in longer immobilization and more days lost at work with significant psychosocial and financial consequences. Initially Pulsed Electromagnetic Fields was used in the treatment of tibial pseudoarthrosis and non-union. More recently there is evidence that physical forces can also be used in the treatment of fresh fractures, showing accelerated healing by 30% and 71% reduction in nonunion within 12 weeks after initiation of therapy. Until now no double blind randomized, placebo controlled trial has been conducted to investigate the effect of this treatment on the healing of fresh fractures of the scaphoid. Methods/Design This is a multi center, prospective, double blind, placebo controlled, randomized trial. Study population consists of all patients with unilateral acute scaphoid fracture. Pregnant women, patients having a life supporting implanted electronic device, patients with additional fractures of wrist, carpal or metacarpal bones and pre-existing impairment in wrist function are excluded. The scaphoid fracture is diagnosed by a combination of physical and radiographic examination (CT-scanning). Proven scaphoid fractures are treated with cast immobilization and a small Pulsed Electromagnetic Fields bone growth stimulating device placed on the cast. Half of the devices will be disabled at random in the factory. Study parameters are clinical consolidation, radiological consolidation evaluated by CT-scanning, functional status of the wrist, including assessment by means of the patient rated wrist evaluation (PRWE) questionnaire and quality of life using SF-36 health survey questionnaire. Primary endpoint is number of scaphoid unions at six weeks, secondary endpoints are time interval to clinical and radiological consolidation, number of non-unions, functional status at 52 weeks and non-adherence to the treatment protocol. Trial registration Netherlands Trial Register (NTR): NTR2064 PMID:21548951

[Constraints on publication rights in industry-initiated clinical trials--secondary publication].

PubMed

Gøtzsche, Peter C; Hróbjartsson, Asbjørn; Johansen, Helle Krogh; Haahr, Mette T; Altman, Douglas G; Chan, An-Wen

2006-06-19

In 22 of 44 industry-initiated clinical trial protocols from 1994-95, it was noted that the sponsor either owned the data or needed to approve the manuscript; another 18 protocols had other constraints. Furthermore, in 16 trials, the sponsor had access to accumulating data, and in an additional 16 trials the sponsor could stop the trial at any time, for any reason. These facts were not noted in any of the trial reports. We found similar constraints on publication rights in 44 protocols from 2004. This tight sponsor control over industry-initiated trials should be changed.

It’s plain and simple: transparency is good for science and in the public interest

PubMed Central

2013-01-01

In the past couple of years, there has been a growing focus on the need to make scientific output accessible to a greater number of people, especially in the field of clinical research. The public are being urged to become more well-informed and to ask their doctors about taking part in clinical trials. A key finding of a report from the Association of Medical Research Charities was that all published scientific papers would benefit from having a section in plain English. Researchers running a clinical trial are expected to provide a summary of their intended research at various stages of the research process. However, there is evidence that existing summaries are of variable length and quality and not always in plain English. As a result, the National Institute for Health Research (NIHR) commissioned a review of the guidance that is available to researchers. However, recent initiatives demonstrate that there are still a number of challenges in making current research both accessible and understandable by prospective participants. BioMed Central also has a number of ongoing initiatives involving trial registration services and journals. PMID:23849479

Transcatheter Aortic Valve Implantation: Experience with the CoreValve Device.

PubMed

Asgar, Anita W; Bonan, Raoul

2012-01-01

The field of transcatheter aortic valve implantation has been rapidly evolving. The Medtronic CoreValve first emerged on the landscape in 2004 with initial first human studies, and it is currently being studied in the Pivotal US trial. This article details the current experience with the self-expanding aortic valve with a focus on clinical results and ongoing challenges. Copyright © 2012 Elsevier Inc. All rights reserved.

Development of the adult PedsQL™ neurofibromatosis type 1 module: initial feasibility, reliability and validity.

PubMed

Nutakki, Kavitha; Hingtgen, Cynthia M; Monahan, Patrick; Varni, James W; Swigonski, Nancy L

2013-02-21

Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder with significant impact on health-related quality of life (HRQOL). Research in understanding the pathogenetic mechanisms of neurofibroma development has led to the use of new clinical trials for the treatment of NF1. One of the most important outcomes of a trial is improvement in quality of life, however, no condition specific HRQOL instrument for NF1 exists. The objective of this study was to develop an NF1 HRQOL instrument as a module of PedsQL™ and to test for its initial feasibility, internal consistency reliability and validity in adults with NF1. The NF1 specific HRQOL instrument was developed using a standard method of PedsQL™ module development - literature review, focus group/semi-structured interviews, cognitive interviews and experts' review of initial draft, pilot testing and field testing. Field testing involved 134 adults with NF1. Feasibility was measured by the percentage of missing responses, internal consistency reliability was measured with Cronbach's alpha and validity was measured by the known-groups method. Feasibility, measured by the percentage of missing responses was 4.8% for all subscales on the adult version of the NF1-specific instrument. Internal consistency reliability for the Total Score (alpha =0.97) and subscale reliabilities ranging from 0.72 to 0.96 were acceptable for group comparisons. The PedsQL™ NF1 module distinguished between NF1 adults with excellent to very good, good, and fair to poor health status. The results demonstrate the initial feasibility, reliability and validity of the PedsQL™ NF1 module in adult patients. The PedsQL™ NF1 Module can be used to understand the multidimensional nature of NF1 on the HRQOL patients with this disorder.

Research Areas - Clinical Trials

Cancer.gov

Information about NCI programs and initiatives that sponsor, conduct, develop, or support clinical trials, including NCI’s Clinical Trial Network (NCTN) and NCI Community Oncology Research Program (NCORP) initiatives.

The development of expertise using an intelligent computer-aided training system

NASA Technical Reports Server (NTRS)

Johnson, Debra Steele

1991-01-01

An initial examination was conducted of an Intelligent Tutoring System (ITS) developed for use in industry. The ITS, developed by NASA, simulated a satellite deployment task. More specifically, the PD (Payload Assist Module Deployment)/ICAT (Intelligent Computer Aided Training) System simulated a nominal Payload Assist Module (PAM) deployment. The development of expertise on this task was examined using three Flight Dynamics Officer (FDO) candidates who has no previous experience with this task. The results indicated that performance improved rapidly until Trial 5, followed by more gradual improvements through Trial 12. The performance dimensions measured included performance speed, actions completed, errors, help required, and display fields checked. Suggestions for further refining the software and for deciding when to expose trainees to more difficult task scenarios are discussed. Further, the results provide an initial demonstration of the effectiveness of the PD/ICAT system in training the nominal PAM deployment task and indicate the potential benefits of using ITS's for training other FDO tasks.

The development of expertise on an intelligent tutoring system

NASA Technical Reports Server (NTRS)

Johnson, Debra Steele

1989-01-01

An initial examination was conducted of an Intelligent Tutoring System (ITS) developed for use in industry. The ITS, developed by NASA, simulated a satellite deployment task. More specifically, the PD (Payload Assist Module Deployment)/ICAT (Intelligent Computer Aided Training) System simulated a nominal Payload Assist Module (PAM) deployment. The development of expertise on this task was examined using three Flight Dynamics Officer (FDO) candidates who had no previous experience with this task. The results indicated that performance improved rapidly until Trial 5, followed by more gradual improvements through Trial 12. The performance dimensions measured included performance speed, actions completed, errors, help required, and display fields checked. Suggestions for further refining the software and for deciding when to expose trainees to more difficult task scenarios are discussed. Further, the results provide an initial demonstration of the effectiveness of the PD/ICAT system in training the nominal PAM deployment task and indicate the potential benefits of using ITS's for training other FDO tasks.

Field Level RNAi-Mediated Resistance to Cassava Brown Streak Disease across Multiple Cropping Cycles and Diverse East African Agro-Ecological Locations

PubMed Central

Wagaba, Henry; Beyene, Getu; Aleu, Jude; Odipio, John; Okao-Okuja, Geoffrey; Chauhan, Raj Deepika; Munga, Theresia; Obiero, Hannington; Halsey, Mark E.; Ilyas, Muhammad; Raymond, Peter; Bua, Anton; Taylor, Nigel J.; Miano, Douglas; Alicai, Titus

2017-01-01

Cassava brown streak disease (CBSD) presents a serious threat to cassava production in East and Central Africa. Currently, no cultivars with high levels of resistance to CBSD are available to farmers. Transgenic RNAi technology was employed to combat CBSD by fusing coat protein (CP) sequences from Ugandan cassava brown streak virus (UCBSV) and Cassava brown streak virus (CBSV) to create an inverted repeat construct (p5001) driven by the constitutive Cassava vein mosaic virus promoter. Twenty-five plant lines of cultivar TME 204 expressing varying levels of small interfering RNAs (siRNAs) were established in confined field trials (CFTs) in Uganda and Kenya. Within an initial CFT at Namulonge, Uganda, non-transgenic TME 204 plants developed foliar and storage root CBSD incidences at 96–100% by 12 months after planting. In contrast, 16 of the 25 p5001 transgenic lines showed no foliar symptoms and had less than 8% of their storage roots symptomatic for CBSD. A direct positive correlation was seen between levels of resistance to CBSD and expression of transgenic CP-derived siRNAs. A subsequent CFT was established at Namulonge using stem cuttings from the initial trial. All transgenic lines established remained asymptomatic for CBSD, while 98% of the non-transgenic TME 204 stake-derived plants developed storage roots symptomatic for CBSD. Similarly, very high levels of resistance to CBSD were demonstrated by TME 204 p5001 RNAi lines grown within a CFT over a full cropping cycle at Mtwapa, coastal Kenya. Sequence analysis of CBSD causal viruses present at the trial sites showed that the transgenic lines were exposed to both CBSV and UCBSV, and that the sequenced isolates shared >90% CP identity with transgenic CP sequences expressed by the p5001 inverted repeat expression cassette. These results demonstrate very high levels of field resistance to CBSD conferred by the p5001 RNAi construct at diverse agro-ecological locations, and across the vegetative cropping cycle. PMID:28127301

Experiences of being a control group: lessons from a UK-based randomized controlled trial of group singing as a health promotion initiative for older people.

PubMed

Skingley, Ann; Bungay, Hilary; Clift, Stephen; Warden, June

2014-12-01

Existing randomized controlled trials within the health field suggest that the concept of randomization is not always well understood and that feelings of disappointment may occur when participants are not placed in their preferred arm. This may affect a study's rigour and ethical integrity if not addressed. We aimed to test whether these issues apply to a healthy volunteer sample within a health promotion trial of singing for older people. Written comments from control group participants at two points during the trial were analysed, together with individual semi-structured interviews with a small sample (n = 11) of this group. We found that motivation to participate in the trial was largely due to the appeal of singing and disappointment resulted from allocation to the control group. Understanding of randomization was generally good and feelings of disappointment lessened over time and with a post-research opportunity to sing. Findings suggest that measures should be put in place to minimize the potential negative impacts of randomized controlled trials in health promotion research. © The Author (2013). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Factors predicting publication of spinal cord injury trials registered on www.ClinicalTrials. gov.

PubMed

DePasse, J Mason; Park, Sara; Eltorai, Adam E M; Daniels, Alan H

2018-02-06

Treatment options for spinal cord injuries are currently limited, but multiple clinical trials are underway for a variety of interventions, drugs, and devices. The Food and Drug Administration website www.ClinicalTrials.gov catalogues these trials and includes information on the status of the trial, date of initiation and completion, source of funding, and region. This investigation assesses the factors associated with publication and the publication rate of spinal cord injury trials. Retrospective analysis of publically available data on www.ClinicalTrials.gov. The www.ClinicalTrials.gov was queried for all trials on patients with spinal cord injury, and these trials were assessed for status, type of intervention, source of funding, and region. Multiple literature searches were performed on all completed trials to determine publication status. There were 626 studies identified concerning the treatment of patients with spinal cord injury, of which 250 (39.9%) were completed. Of these, only 119 (47.6%) were published. There was no significant difference in the rate of publication between regions (p> 0.16) or by study type (p> 0.29). However, trials that were funded by the NIH were more likely to be published than trials funded by industry (p= 0.01). The current publication rate of spinal cord injury trials is only 47.6%, though this rate is similar to the publication rate for trials in other fields. NIH-funded trials are significantly more likely to become published than industry-funded trials, which could indicate that some trials remain unpublished due to undesirable results. However, it is also likely that many trials on spinal cord injury yield negative results, as treatments are often ineffective.

Clinical trials involving positron emission tomography and prostate cancer: an analysis of the ClinicalTrials.gov database.

PubMed

Cihoric, Nikola; Vlaskou Badra, Eugenia; Tsikkinis, Alexandros; Prasad, Vikas; Kroeze, Stephanie; Igrutinovic, Ivan; Jeremic, Branislav; Beck, Marcus; Zschaeck, Sebastian; Wust, Peter; Ghadjar, Pirus

2018-06-18

The goal of this study is to evaluate the status and future perspectives of clinical trials on positron emission tomography in prostate cancer for diagnostic or therapeutic as well as for surveillance purposes. The www.ClinicalTrials.gov database was searched on the 20th of January 2017 for all trials containing terms describing "prostate cancer" (prostate, prostatic, malignant, malignancy, cancer, tumor) and "positron emission tomography". In total 167 trials were identified. Trials that included diseases other than PCa were excluded (n = 27; 16%). Furthermore, we excluded trials (n = 4, 2%) withdrawn prior to first patient enrollment. The remaining trials (n = 137, 82%) were selected for further manual classification analysis. One hundred thirty-seven trials were detected and analyzed. Majority of trials were in "active" recruitment status (n = 46, 34%) followed by trials that had been "completed" - (n = 34, 25%) and trials with "closed recruitment but active follow-up" (n = 23, 17%). Phase 1 and 2 comprised 46% of the complete trial portfolio. Locally confined disease was of major interest (n = 46, 34%), followed by metastatic disease - not otherwise specified (n = 43, 13%). Evaluation of PET was the primary goal of the trial in 114 (83%) cases. Most of the trials evaluated only one agent (n = 122, 89%). Choline and PSMA represented two major groups (total 50%) and they were equally distributed across trial portfolio with 25% (n = 34) each. PSMA trials showed the highest average annual growth rate of 56%. The trials were conducted in 17 countries. The scientific community is showing a strong and ever-growing interest in the field and we expect that in the coming years, more phase III trials will be initiated ultimately delivering the required Level 1 evidence.

Litter quality impacts short- but not long-term soil carbon dynamics in soil aggregate fractions.

PubMed

Gentile, Roberta; Vanlauwe, Bernard; Six, Johan

2011-04-01

Complex molecules are presumed to be preferentially stabilized as soil organic carbon (SOC) based on the generally accepted concept that the chemical composition of litter is a major factor in its rate of decomposition. Hence, a direct link between litter quality and SOC quantity has been assumed, accepted, and ultimately incorporated in SOC models. Here, however, we present data from an incubation and field experiment that refutes the influence of litter quality on the quantity of stabilized SOC. Three different qualities of litter (Tithonia diversifolia, Calliandra calothyrsus, and Zea mays stover; 4 Mg C x ha(-1) yr(-1)) with and without the addition of mineral N fertilizer (0 or 120 kg N x ha(-1)season(-1) were added to a red clay Humic Nitisol in a 3-yr field trial and a 1.5-yr incubation experiment. The litters differed in their concentrations of N, lignin, and polyphenols with the ratio of (lignin + polyphenols): N ranging from 3.5 to 9.8 for the field trial and from 2.3 to 4.0 for the incubation experiment in the order of T. diversifolia < C. calothyrsus < or = Z. mays. Litter quality did not affect the amount of SOC stabilized after three annual additions in the field trial. Even within the most sensitive soil aggregate fractions, SOC contents and C:N ratios did not differ with litter quality, indicating that litter quality did not influence the mechanisms by which SOC was stabilized. While increasing litter quality displayed faster decomposition and incorporation of C into soil aggregates after 0.25 yr in the incubation study, all litters resulted in equivalent amounts of C stabilized in the soil after 1.5 yr, further corroborating the results of the field trial. The addition of N fertilizer did not affect SOC stabilization in either the field or the incubation trial. Thus, we conclude that, while litter quality controls shorter-term dynamics of C decomposition and accumulation in the soil, longer-term SOC patterns cannot be predicted based on initial litter quality effects. Hence, the formation and stabilization of SOC is more controlled by the quantity of litter input and its interaction with the soil matrix than by litter quality.

Description and Evaluation of a Four-Channel, Coherent 100-kHz Sidescan Sonar

DTIC Science & Technology

2004-12-01

document contains color images. 14. ABSTRACT This report documents the design and features of a new, four-channel, coherent 100-kHz sidescan sonar...Atlantic Technical Memorandum DRDC Atlantic TM 2004-204 December 2004 Abstract This report documents the design and features of a new...Results This report documents the design and features of this new high-frequency sonar system. These initial field trial results demonstrate some of

The Laser in Glaucoma and Ocular Hypertension (LiGHT) trial. A multicentre randomised controlled trial: baseline patient characteristics.

PubMed

Konstantakopoulou, Evgenia; Gazzard, Gus; Vickerstaff, Victoria; Jiang, Yuzhen; Nathwani, Neil; Hunter, Rachael; Ambler, Gareth; Bunce, Catey

2018-05-01

The laser in glaucoma and ocular hypertension (LiGHT) trial aims to establish whether initial treatment with selective laser trabeculoplasty (SLT) is superior to initial treatment with topical medication for primary open angle glaucoma (POAG) or ocular hypertension (OHT). LiGHT is a prospective unmasked, multicentre, pragmatic, randomised controlled trial (RCT). 718 previously untreated patients with POAG or OHT were recruited at 6 UK centres between 2012 and 2014. Patients were randomised to initial SLT followed by medical therapy or medical therapy without laser. Participants will be monitored for 3 years, according to routine clinical practice. The primary outcome is EQ-5D-5L. Secondary outcomes are treatment pathway cost and cost-effectiveness, Glaucoma Utility Index (GUI), Glaucoma Symptom Scale, Glaucoma Quality of Life (GQL), pathway effectiveness, visual function, safety and concordance. A total of 555 patients had POAG and 163 OHT; 518 patients had both eyes eligible. The mean age for patients with POAG was 64 years and for OHT 58 years. 70% of all participants were white. Median IOP for OHT eyes was 26 mm Hg and 23 mm Hg for POAG eyes. Median baseline visual field mean deviation was -0.81 dB for OHT eyes and -2.82 dB for POAG eyes. There was no difference between patients with POAG and patients with OHT on the EQ-5D-5DL; the difference between OHT and POAG on the GUI was -0.02 and 1.23 on the GQL. The LiGHT trial is the first RCT to compare the two treatment options in a real-world setting. The baseline characteristics of the LiGHT cohort compare well with other landmark glaucoma studies. ISRCTN32038223, Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Feedforward compensation for novel dynamics depends on force field orientation but is similar for the left and right arms.

PubMed

Reuter, Eva-Maria; Cunnington, Ross; Mattingley, Jason B; Riek, Stephan; Carroll, Timothy J

2016-11-01

There are well-documented differences in the way that people typically perform identical motor tasks with their dominant and the nondominant arms. According to Yadav and Sainburg's (Neuroscience 196: 153-167, 2011) hybrid-control model, this is because the two arms rely to different degrees on impedance control versus predictive control processes. Here, we assessed whether differences in limb control mechanisms influence the rate of feedforward compensation to a novel dynamic environment. Seventy-five healthy, right-handed participants, divided into four subsamples depending on the arm (left, right) and direction of the force field (ipsilateral, contralateral), reached to central targets in velocity-dependent curl force fields. We assessed the rate at which participants developed predictive compensation for the force field using intermittent error-clamp trials and assessed both kinematic errors and initial aiming angles in the field trials. Participants who were exposed to fields that pushed the limb toward ipsilateral space reduced kinematic errors more slowly, built up less predictive field compensation, and relied more on strategic reaiming than those exposed to contralateral fields. However, there were no significant differences in predictive field compensation or kinematic errors between limbs, suggesting that participants using either the left or the right arm could adapt equally well to novel dynamics. It therefore appears that the distinct preferences in control mechanisms typically observed for the dominant and nondominant arms reflect a default mode that is based on habitual functional requirements rather than an absolute limit in capacity to access the controller specialized for the opposite limb. Copyright © 2016 the American Physiological Society.

Feedforward compensation for novel dynamics depends on force field orientation but is similar for the left and right arms

PubMed Central

Cunnington, Ross; Mattingley, Jason B.; Riek, Stephan; Carroll, Timothy J.

2016-01-01

There are well-documented differences in the way that people typically perform identical motor tasks with their dominant and the nondominant arms. According to Yadav and Sainburg's (Neuroscience 196: 153–167, 2011) hybrid-control model, this is because the two arms rely to different degrees on impedance control versus predictive control processes. Here, we assessed whether differences in limb control mechanisms influence the rate of feedforward compensation to a novel dynamic environment. Seventy-five healthy, right-handed participants, divided into four subsamples depending on the arm (left, right) and direction of the force field (ipsilateral, contralateral), reached to central targets in velocity-dependent curl force fields. We assessed the rate at which participants developed predictive compensation for the force field using intermittent error-clamp trials and assessed both kinematic errors and initial aiming angles in the field trials. Participants who were exposed to fields that pushed the limb toward ipsilateral space reduced kinematic errors more slowly, built up less predictive field compensation, and relied more on strategic reaiming than those exposed to contralateral fields. However, there were no significant differences in predictive field compensation or kinematic errors between limbs, suggesting that participants using either the left or the right arm could adapt equally well to novel dynamics. It therefore appears that the distinct preferences in control mechanisms typically observed for the dominant and nondominant arms reflect a default mode that is based on habitual functional requirements rather than an absolute limit in capacity to access the controller specialized for the opposite limb. PMID:27582293

[Non-commercial clinical trials--who will be the legal sponsor? Sponsorship of investigator-initiated clinical trials according to the German Drug Law].

PubMed

Benninger-Döring, G; Boos, J

2006-07-01

Non-commercial clinical trials may be of great benefit to the patients concerned. The 12th amendment to the German Drug Law (AMG) changed legal liability of the initiators of investigator-initiated clinical trials with extensive consequences for traditional project leaders. The central point under discussion is the sponsor's responsibility according to the AMG. Presently leading management divisions of university hospitals and universities are developing proceedings to assume sponsor responsibility by institutions (institutional sponsorship), which should enable investigator-initiated clinical trials to be conducted according to legal requirements in the future. Detailed problems and special questions can only be resolved in a single-minded fashion, and if necessary political processes should be catalyzed.

Understanding the investigators: a qualitative study investigating the barriers and enablers to the implementation of local investigator-initiated clinical trials in Ethiopia

PubMed Central

Franzen, Samuel R P; Chandler, Clare; Enquselassie, Fikre; Siribaddana, Sisira; Atashili, Julius; Angus, Brian; Lang, Trudie

2013-01-01

Objectives Clinical trials provide ‘gold standard’ evidence for policy, but insufficient locally relevant trials are conducted in low-income and middle-income countries. Local investigator-initiated trials could generate highly relevant data for national governments, but information is lacking on how to facilitate them. We aimed to identify barriers and enablers to investigator-initiated trials in Ethiopia to inform and direct capacity strengthening initiatives. Design Exploratory, qualitative study comprising of in-depth interviews (n=7) and focus group discussions (n=3). Setting Fieldwork took place in Ethiopia during March 2011. Participants Local health researchers with previous experiences of clinical trials or stakeholders with an interest in trials were recruited through snowball sampling (n=20). Outcome measures Detailed discussion notes were analysed using thematic coding analysis and key themes were identified. Results All participants perceived investigator-initiated trials as important for generating local evidence. System and organisational barriers included: limited funding allocation, weak regulatory and administrative systems, few learning opportunities, limited human and material capacity and poor incentives for conducting research. Operational hurdles were symptomatic of these barriers. Lack of awareness, confidence and motivation to undertake trials were important individual barriers. Training, knowledge sharing and experience exchange were key enablers to trial conduct and collaboration was unanimously regarded as important for improving capacity. Conclusions Barriers to trial conduct were found at individual, operational, organisational and system levels. These findings indicate that to increase locally led trial conduct in Ethiopia, system wide changes are needed to create a more receptive and enabling research environment. Crucially, the creation of research networks between potential trial groups could provide much needed practical collaborative support through sharing of financial and project management burdens, knowledge and resources. These findings could have important implications for capacity-strengthening initiatives but further research is needed before the results can be generalised more widely. PMID:24285629

The Future of HIV Vaccine Research and the Role of the Global HIV Vaccine Enterprise

PubMed Central

Voronin, Yegor; Manrique, Amapola; Bernstein, Alan

2010-01-01

Purpose of review This review covers the role of the Global HIV Vaccine Enterprise (the Enterprise), an alliance of independent organizations committed to development of a safe and effective HIV vaccine. It discussesthe history, impact on the field and future directions and initiatives of the alliance, in the context of recent progress in HIV vaccine research and development. Recent Findings Significant progress has been made in the field since the release of the 2005 Scientific Strategic Plan (The Plan) of the Enterprise. Over the last year, the Enterprise embarked on an impact assessment of the 2005 Planand the development of the 2010 Plan. Enterprise Working Groups identified key priorities in the field, several of which are discussed in this review, including: changing the nature, purpose and process of clinical trials; increasing and facilitating data sharing; and optimizing existing and attracting new resources. Summary This isan important moment in HIV vaccine research. New clinical trial and laboratory results have created new opportunities to advance the search for an HIV vaccineand reinvigorated the field. The Enterprise will publish its 2010 Scientific Strategic Planthis year, providinga framework for setting new priorities and directions, and encouraging new and existing partners to embark on a shared scientific agenda. PMID:20978383

The future of HIV vaccine research and the role of the Global HIV Vaccine Enterprise.

PubMed

Voronin, Yegor; Manrique, Amapola; Bernstein, Alan

2010-09-01

This review covers the role of the Global HIV Vaccine Enterprise (the Enterprise), an alliance of independent organizations committed to development of a safe and effective HIV vaccine. It discusses the history, impact on the field, and future directions and initiatives of the alliance in the context of recent progress in HIV vaccine research and development. Significant progress has been made in the field since the release of the 2005 Scientific Strategic Plan (the Plan) of the Enterprise. Over the last year, the Enterprise embarked on an impact assessment of the 2005 Plan and the development of the 2010 Plan. Enterprise Working Groups identified key priorities in the field, several of which are discussed in this review, including changing the nature, purpose and process of clinical trials, increasing and facilitating data sharing, and optimizing existing and mobilizing new resources. This time is an important moment in HIV vaccine research. New clinical trial and laboratory results have created new opportunities to advance the search for an HIV vaccine and reinvigorated the field. The Enterprise will publish its 2010 Plan this year, providing a framework for setting new priorities and directions and encouraging new and existing partners to embark on a shared scientific agenda.

Biomass power for rural development. Technical progress report, May 1, 1996--December 31, 1996

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neuhauser, E.

Developing commercial energy crops for power generation by the year 2000 is the focus of the DOE/USDA sponsored Biomass Power for Rural Development project. The New York based Salix Consortium project is a multi-partner endeavor, implemented in three stages. Phase-I, Final Design and Project Development, will conclude with the preparation of construction and/or operating permits, feedstock production plans, and contracts ready for signature. Field trials of willow (Salix) have been initiated at several locations in New York (Tully, Lockport, King Ferry, La Facette, Massena, and Himrod) and co-firing tests are underway at Greenidge Station (NYSEG). Phase-II of the project willmore » focus on scale-up of willow crop acreage, construction of co-firing facilities at Dunkirk Station (NMPC), and final modifications for Greenidge Station. There will be testing of the energy crop as part of the gasification trials expected to occur at BED`s McNeill power station and potentially at one of GPU`s facilities. Phase-III will represent full-scale commercialization of the energy crop and power generation on a sustainable basis. Willow has been selected as the energy crop of choice for many reasons. Willow is well suited to the climate of the Northeastern United States, and initial field trials have demonstrated that the yields required for the success of the project are obtainable. Like other energy crops, willow has rural development benefits and could serve to diversify local crop production, provide new sources of income for participating growers, and create new jobs. Willow could be used to put a large base of idle acreage back into crop production. Additionally, the willow coppicing system integrates well with current farm operations and utilizes agricultural practices that are already familiar to farmers.« less

The Cryptophlebia Leucotreta Granulovirus—10 Years of Commercial Field Use

PubMed Central

Moore, Sean D.; Kirkman, Wayne; Richards, Garth I.; Stephen, Peter R.

2015-01-01

In the last 15 years, extensive work on the Cryptophlebia leucotreta granulovirus (CrleGV) has been conducted in South Africa, initially in the laboratory, but subsequently also in the field. This culminated in the registration of the first CrleGV-based biopesticide in 2004 (hence, the 10 years of commercial use in the field) and the second one three years later. Since 2000, more than 50 field trials have been conducted with CrleGV against the false codling moth, Thaumatotibia leucotreta, on citrus in South Africa. In a representative sample of 13 field trials reported over this period, efficacy (measured by reduction in larval infestation of fruit) ranged between 30% and 92%. Efficacy was shown to persist at a level of 70% for up to 17 weeks after application of CrleGV. This only occurred where the virus was applied in blocks rather than to single trees. The addition of molasses substantially and sometimes significantly enhanced efficacy. It was also established that CrleGV should not be applied at less than ~2 × 1013 OBs per ha in order to avoid compromised efficacy. As CrleGV-based products were shown to be at least as effective as chemical alternatives, persistent and compatible with natural enemies, their use is recommended within an integrated program for control of T. leucotreta on citrus and other crops. PMID:25809025

No reliable evidence to guide initial arch wire choice for fixed appliance therapy.

PubMed

Flores-Mir, Carlos

2013-12-01

The Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline and Embase databases were searched. Conference proceedings and abstracts from the British Orthodontic Conference European Orthodontic Conference and the International Association for Dental Research were also searched together with the reference lists of identified studies. Study authors were contacted for additional information. Randomised controlled trials of initial arch wire involving participants with upper and/or lower full arch fixed orthodontic appliances were included. Study selection, data extraction and risk of bias assessment were carried out independently by at least two reviewers. Nine RCTs with 571 participants were included in this review. All trials were at high risk of bias. All trials had at least one potentially confounding factor (such as bracket type, slot size, ligation method, extraction of teeth) which is likely to have influenced the outcome and was not controlled in the trial. None of the trials reported the important adverse outcome of root resorption. The comparisons were made between:Multistrand stainless steel initial arch wires compared to superelastic nickel titanium (NiTi) initial arch wires. There were four trials in this group, with different comparisons and outcomes reported at different times. No meta-analysis was possible. There is insufficient evidence from these trials to determine whether or not there is a difference in either rate of alignment or pain between stainless steel and NiTi initial arch wires.Conventional (stabilised) NiTi initial arch wires compared to superelastic NiTi initial arch wires. There were two trials in this group, one reporting the outcome of alignment over six months and the other reporting pain over one week. There is insufficient evidence from these trials to determine whether or not there is any difference between conventional (stabilised) and superelastic NiTi initial arch wires with regard to either alignment or pain.Single-strand superelastic NiTi initial arch wires compared to other NiTi (coaxial, copper NiTi (CuNiTi) or thermoelastic) initial arch wires. The three trials in this comparison each compared a different product against single-strand superelastic NiTi. There is very weak unreliable evidence, based on one very small study (n = 24) at high risk of bias, that coaxial superelastic NiTi may produce greater tooth movement over 12 weeks, but no information on associated pain or root resorption. This result should be interpreted with caution until further research evidence is available. There is insufficient evidence to determine whether or not there is a difference between either thermoelastic or CuNiTi and superelastic NiTi initial arch wires. There is no reliable evidence from the trials included in this review that any specific initial arch wire material is better or worse than another with regard to speed of alignment or pain. There is no evidence at all about the effect of initial arch wire materials on the important adverse effect of root resorption. Further well-designed and conducted, adequately-powered RCTs are required to determine whether the performance of initial arch wire materials as demonstrated in the laboratory, makes a clinically important difference to the alignment of teeth in the initial stage of orthodontic treatment in patients.

Patients or volunteers? The impact of motivation for trial participation on the efficacy of patient decision Aids: a secondary analysis of a Cochrane systematic review.

PubMed

Brown, James G; Joyce, Kerry E; Stacey, Dawn; Thomson, Richard G

2015-05-01

Efficacy of patient decision aids (PtDAs) may be influenced by trial participants' identity either as patients seeking to benefit personally from involvement or as volunteers supporting the research effort. To determine if study characteristics indicative of participants' trial identity might influence PtDA efficacy. We undertook exploratory subgroup meta-analysis of the 2011 Cochrane review of PtDAs, including trials that compared PtDA with usual care for treatment decisions. We extracted data on whether participants initiated the care pathway, setting, practitioner interactions, and 6 outcome variables (knowledge, risk perception, decisional conflict, feeling informed, feeling clear about values, and participation). The main subgroup analysis categorized trials as "volunteerism" or "patienthood" on the basis of whether participants initiated the care pathway. A supplementary subgroup analysis categorized trials on the basis of whether any volunteerism factors were present (participants had not initiated the care pathway, had attended a research setting, or had a face-to-face interaction with a researcher). Twenty-nine trials were included. Compared with volunteerism trials, pooled effect sizes were higher in patienthood trials (where participants initiated the care pathway) for knowledge, decisional conflict, feeling informed, feeling clear, and participation. The subgroup difference was statistically significant for knowledge only (P = 0.03). When trials were compared on the basis of whether volunteerism factors were present, knowledge was significantly greater in patienthood trials (P < 0.001), but there was otherwise no consistent pattern of differences in effects across outcomes. There is a tendency toward greater PtDA efficacy in trials in which participants initiate the pathway of care. Knowledge acquisition appears to be greater in trials where participants are predominantly patients rather than volunteers. © The Author(s) 2015.

Catch trials in force field learning influence adaptation and consolidation of human motor memory

PubMed Central

Stockinger, Christian; Focke, Anne; Stein, Thorsten

2014-01-01

Force field studies are a common tool to investigate motor adaptation and consolidation. Thereby, subjects usually adapt their reaching movements to force field perturbations induced by a robotic device. In this context, so-called catch trials, in which the disturbing forces are randomly turned off, are commonly used to detect after-effects of motor adaptation. However, catch trials also produce sudden large motor errors that might influence the motor adaptation and the consolidation process. Yet, the detailed influence of catch trials is far from clear. Thus, the aim of this study was to investigate the influence of catch trials on motor adaptation and consolidation in force field experiments. Therefore, 105 subjects adapted their reaching movements to robot-generated force fields. The test groups adapted their reaching movements to a force field A followed by learning a second interfering force field B before retest of A (ABA). The control groups were not exposed to force field B (AA). To examine the influence of diverse catch trial ratios, subjects received catch trials during force field adaptation with a probability of either 0, 10, 20, 30, or 40%, depending on the group. First, the results on motor adaptation revealed significant differences between the diverse catch trial ratio groups. With increasing amount of catch trials, the subjects' motor performance decreased and subjects' ability to accurately predict the force field—and therefore internal model formation—was impaired. Second, our results revealed that adapting with catch trials can influence the following consolidation process as indicated by a partial reduction to interference. Here, the optimal catch trial ratio was 30%. However, detection of consolidation seems to be biased by the applied measure of performance. PMID:24795598

Telling our stories: heroin-assisted treatment and SNAP activism in the Downtown Eastside of Vancouver.

PubMed

Boyd, Susan; Murray, Dave; MacPherson, Donald

2017-05-18

This article highlights the experiences of a peer-run group, SALOME/NAOMI Association of Patients (SNAP), that meets weekly in the Downtown Eastside of Vancouver, British Columbia, Canada. SNAP is a unique independent peer- run drug user group that formed in 2011 following Canada's first heroin-assisted treatment trial (HAT), North America Opiate Medication Initiative (NAOMI). SNAP's members are now made up of former research participants who participated in two heroin-assisted trials in Vancouver. This article highlights SNAP members' experiences as research subjects in Canada's second clinical trial conducted in Vancouver, Study to Assess Longer-term Opioid Medication Effectiveness (SALOME), that began recruitment of research participants in 2011. This paper draws on one brainstorming session, three focus groups, and field notes, with the SALOME/NAOMI Association of Patients (SNAP) in late 2013 about their experiences as research subjects in Canada's second clinical trial, SALOME in the DTES of Vancouver, and fieldwork from a 6-year period (March 2011 to February 2017) with SNAP members. SNAP's research draws on research principles developed by drug user groups and critical methodological frameworks on community-based research for social justice. The results illuminate how participating in the SALOME clinical trial impacted the lives of SNAP members. In addition, the findings reveal how SNAP member's advocacy for HAT impacts the group in positive ways. Seven major themes emerged from the analysis of the brainstorming and focus groups: life prior to SALOME, the clinic setting and routine, stability, 6-month transition, support, exiting the trial and ethics, and collective action, including their participation in a constitutional challenge in the Supreme Court of BC to continue receiving HAT once the SALOME trial ended. HAT benefits SNAP members. They argue that permanent HAT programs should be established in Canada because they are an effective harm reduction initiative, one that also reduces opioid overdose deaths.

Barriers and Facilitators to Initiating and Completing Time-Limited Trials in Critical Care.

PubMed

Bruce, Courtenay R; Liang, Cecilia; Blumenthal-Barby, Jennifer S; Zimmerman, Janice; Downey, Andrea; Pham, Linda; Theriot, Lisette; Delgado, Estevan D; White, Douglas

2015-12-01

A time-limited trial is an agreement between clinicians and patients or surrogate decision makers to use medical therapies over a defined period of time to see if the patient improves or deteriorates according to agreed-upon clinical milestones. Although time-limited trials are broadly advocated, there is little empirical evidence of the benefits and risks of time-limited trials, when they are initiated, when and why they succeed or fail, and what facilitates completion of them. Our study objectives were to 1) identify the purposes for which clinicians use time-limited trials and 2) identify barriers and facilitators to initiating and completing time-limited trials. Semistructured interviews: We analyzed interviews using qualitative description with constant comparative techniques. Nine hundred-bed, academic, tertiary hospital in Houston, Texas. Interviewees were from open medical, surgical, neurosurgical, and cardiovascular ICUs. Thirty healthcare professionals were interviewed (nine surgeons, 16 intensivists, three nurse practitioners, and two "other" clinicians). None. Interviewees reported initiating time-limited trials for three different purposes: to prepare surrogates and clinicians for discussion and possible shifts toward comfort-care only therapies, build consensus, and refine prognostic information. The main barriers to initiating time-limited trials involve clinicians' or surrogate decision makers' disagreement on setting a time limit. Barriers to completing time-limited trials include 1) requesting more time; 2) communication breakdowns because of rotating call schedules; and 3) changes in clinical course. Finally, facilitators to completing time-limited trials include 1) having defined goals about what could be achieved during an ICU stay, either framed in narrow, numeric terms or broad goals focusing on achievable activities of daily living; 2) applying time-limited trials in certain types of cases; and 3) taking ownership to ensure completion of the trial. An understanding of barriers and facilitators to initiating and completing time-limited trials is an essential first step toward appropriate utilization of time-limited trials in the ICUs, as well as developing educational or communication interventions with clinicians to facilitate time-limited trial use. We provide practical suggestions on patient populations in whom time-limited trials may be successful, the setting, and clinicians likely to benefit from educational interventions, allowing clinicians to have a fuller sense of when and how to use time-limited trials.

Automated Astrometric Analysis of Satellite Observations using Wide-field Imaging

NASA Astrophysics Data System (ADS)

Skuljan, J.; Kay, J.

2016-09-01

An observational trial was conducted in the South Island of New Zealand from 24 to 28 February 2015, as a collaborative effort between the United Kingdom and New Zealand in the area of space situational awareness. The aim of the trial was to observe a number of satellites in low Earth orbit using wide-field imaging from two separate locations, in order to determine the space trajectory and compare the measurements with the predictions based on the standard two-line elements. This activity was an initial step in building a space situational awareness capability at the Defence Technology Agency of the New Zealand Defence Force. New Zealand has an important strategic position as the last land mass that many satellites selected for deorbiting pass before entering the Earth's atmosphere over the dedicated disposal area in the South Pacific. A preliminary analysis of the trial data has demonstrated that relatively inexpensive equipment can be used to successfully detect satellites at moderate altitudes. A total of 60 satellite passes were observed over the five nights of observation and about 2600 images were collected. A combination of cooled CCD and standard DSLR cameras were used, with a selection of lenses between 17 mm and 50 mm in focal length, covering a relatively wide field of view of 25 to 60 degrees. The CCD cameras were equipped with custom-made GPS modules to record the time of exposure with a high accuracy of one millisecond, or better. Specialised software has been developed for automated astrometric analysis of the trial data. The astrometric solution is obtained as a two-dimensional least-squares polynomial fit to the measured pixel positions of a large number of stars (typically 1000) detected across the image. The star identification is fully automated and works well for all camera-lens combinations used in the trial. A moderate polynomial degree of 3 to 5 is selected to take into account any image distortions introduced by the lens. A typical RMS error of the least-squares fit is about 0.1 pixels, which corresponds to about 4 to 10 seconds of arc in the sky, depending on the pixel scale (field of view). This gives a typical uncertainty between 10 and 25 metres in measuring the position of a satellite at a characteristic range of 500 kilometres. The results of this trial have confirmed that wide-field measurements based on standard photographic equipment and using automated astrometric analysis techniques can be used to improve the current orbital models of satellites in low Earth orbit.

Pulsed Electromagnetic Fields in the treatment of fresh scaphoid fractures. A multicenter, prospective, double blind, placebo controlled, randomized trial.

PubMed

Hannemann, Pascal; Göttgens, Kevin W A; van Wely, Bob J; Kolkman, Karel A; Werre, Andries J; Poeze, Martijn; Brink, Peter R G

2011-05-06

The scaphoid bone is the most commonly fractured of the carpal bones. In the Netherlands 90% of all carpal fractures is a fracture of the scaphoid bone. The scaphoid has an essential role in functionality of the wrist, acting as a pivot. Complications in healing can result in poor functional outcome. The scaphoid fracture is a troublesome fracture and failure of treatment can result in avascular necrosis (up to 40%), non-union (5-21%) and early osteo-arthritis (up to 32%) which may seriously impair wrist function. Impaired consolidation of scaphoid fractures results in longer immobilization and more days lost at work with significant psychosocial and financial consequences.Initially Pulsed Electromagnetic Fields was used in the treatment of tibial pseudoarthrosis and non-union. More recently there is evidence that physical forces can also be used in the treatment of fresh fractures, showing accelerated healing by 30% and 71% reduction in nonunion within 12 weeks after initiation of therapy. Until now no double blind randomized, placebo controlled trial has been conducted to investigate the effect of this treatment on the healing of fresh fractures of the scaphoid. This is a multi center, prospective, double blind, placebo controlled, randomized trial. Study population consists of all patients with unilateral acute scaphoid fracture. Pregnant women, patients having a life supporting implanted electronic device, patients with additional fractures of wrist, carpal or metacarpal bones and pre-existing impairment in wrist function are excluded. The scaphoid fracture is diagnosed by a combination of physical and radiographic examination (CT-scanning).Proven scaphoid fractures are treated with cast immobilization and a small Pulsed Electromagnetic Fields bone growth stimulating device placed on the cast. Half of the devices will be disabled at random in the factory.Study parameters are clinical consolidation, radiological consolidation evaluated by CT-scanning, functional status of the wrist, including assessment by means of the patient rated wrist evaluation (PRWE) questionnaire and quality of life using SF-36 health survey questionnaire.Primary endpoint is number of scaphoid unions at six weeks, secondary endpoints are time interval to clinical and radiological consolidation, number of non-unions, functional status at 52 weeks and non-adherence to the treatment protocol. Netherlands Trial Register (NTR): NTR2064. © 2011 Hannemann et al; licensee BioMed Central Ltd.

Clinical trial quality: From supervision to collaboration and beyond.

PubMed

Meeker-O'Connell, Ann; Glessner, Coleen

2018-02-01

Over the past decade, clinical trial quality has evolved from an after-the-fact, reactive activity to one focused on the important work of evidence generation from well-designed trials. This article explores the role the Clinical Trials Transformation Initiative has played in advancing quality as a core element of clinical trial design, through project work that initially focused on monitoring but evolved into a holistic, prospective, and comprehensive quality by design approach to clinical trial design and conduct.

Enhancing clinical evidence by proactively building quality into clinical trials.

PubMed

Meeker-O'Connell, Ann; Glessner, Coleen; Behm, Mark; Mulinde, Jean; Roach, Nancy; Sweeney, Fergus; Tenaerts, Pamela; Landray, Martin J

2016-08-01

Stakeholders across the clinical trial enterprise have expressed concern that the current clinical trial enterprise is unsustainable. The cost and complexity of trials have continued to increase, threatening our ability to generate reliable evidence essential for making appropriate decisions concerning the benefits and harms associated with clinical interventions. Overcoming this inefficiency rests on improving protocol design, trial planning, and quality oversight. The Clinical Trials Transformation Initiative convened a project to evaluate methods to prospectively build quality into the scientific and operational design of clinical trials ("quality-by-design"), such that trials are feasible to conduct and important errors are prevented rather than remediated. A working group evaluated aspects of trial design and oversight and developed the Clinical Trials Transformation Initiative quality-by-design principles document, outlining a series of factors generally relevant to the reliability of trial conclusions and to patient safety. These principles were then applied and further refined during a series of hands-on workshops to evaluate their utility in facilitating proactive, cross-functional dialogue, and decision-making about trial design and planning. Following these workshops, independent qualitative interviews were conducted with 19 workshop attendees to explore the potential challenges for implementing a quality-by-design approach to clinical trials. The Clinical Trials Transformation Initiative project team subsequently developed recommendations and an online resource guide to support implementation of this approach. The Clinical Trials Transformation Initiative quality-by-design principles provide a framework for assuring that clinical trials adequately safeguard participants and provide reliable information on which to make decisions on the effects of treatments. The quality-by-design workshops highlighted the value of active discussions incorporating the different perspectives within and external to an organization (e.g. clinical investigators, research site staff, and trial participants) in improving trial design. Workshop participants also recognized the value of focusing oversight on those aspects of the trial where errors would have a major impact on participant safety and reliability of results. Applying the Clinical Trials Transformation Initiative quality-by-design recommendations and principles should enable organizations to prioritize the most critical determinants of a trial's quality, identify non-essential activities that can be eliminated to streamline trial conduct and oversight, and formulate appropriate plans to define, avoid, mitigate, monitor, and address important errors. © The Author(s) 2016.

SUPERFUND TREATABILITY CLEARINGHOUSE: FULL SCALE ROTARY KILN INCINERATOR FIELD TRIAL: PHASE I, VERIFICATION TRIAL BURN ON DIOXIN/HERBICIDE ORANGE CONTAMINATED SOIL

EPA Science Inventory

This treatability study reports on the results of one of a series of field trials using various remedial action technologies that may be capable of restoring Herbicide Orange (HO)XDioxin contaminated sites. A full-scale field trial using a rotary kiln incinerator capable of pro...

Re-Engineering Alzheimer Clinical Trials: Global Alzheimer's Platform Network.

PubMed

Cummings, J; Aisen, P; Barton, R; Bork, J; Doody, R; Dwyer, J; Egan, J C; Feldman, H; Lappin, D; Truyen, L; Salloway, S; Sperling, R; Vradenburg, G

2016-06-01

Alzheimer's disease (AD) drug development is costly, time-consuming, and inefficient. Trial site functions, trial design, and patient recruitment for trials all require improvement. The Global Alzheimer Platform (GAP) was initiated in response to these challenges. Four GAP work streams evolved in the US to address different trial challenges: 1) registry-to-cohort web-based recruitment; 2) clinical trial site activation and site network construction (GAP-NET); 3) adaptive proof-of-concept clinical trial design; and 4) finance and fund raising. GAP-NET proposes to establish a standardized network of continuously funded trial sites that are highly qualified to perform trials (with established clinical, biomarker, imaging capability; certified raters; sophisticated management system. GAP-NET will conduct trials for academic and biopharma industry partners using standardized instrument versions and administration. Collaboration with the Innovative Medicines Initiative (IMI) European Prevention of Alzheimer's Disease (EPAD) program, the Canadian Consortium on Neurodegeneration in Aging (CCNA) and other similar international initiatives will allow conduct of global trials. GAP-NET aims to increase trial efficiency and quality, decrease trial redundancy, accelerate cohort development and trial recruitment, and decrease trial costs. The value proposition for sites includes stable funding and uniform training and trial execution; the value to trial sponsors is decreased trial costs, reduced time to execute trials, and enhanced data quality. The value for patients and society is the more rapid availability of new treatments for AD.

COMBAT: Initial experience with a randomized clinical trial of plasma-based resuscitation in the field for traumatic hemorrhagic shock

PubMed Central

Chapman, Michael P.; Moore, Ernest E.; Chin, Theresa L; Ghasabyan, Arsen; Chandler, James; Stringham, John; Gonzalez, Eduardo; Moore, Hunter B.; Banerjee, Anirban; Silliman, Christopher C; Sauaia, Angela

2015-01-01

The existing evidence shows great promise for plasma as the first resuscitation fluid in both civilian and military trauma. We embarked on the Control of Major Bleeding After Trauma (COMBAT) trial with the support of the Department of Defense, in order to determine if plasma-first resuscitation yields hemostatic and survival benefits. The methodology of the COMBAT study represents not only three years of development work, but the integration of nearly two-decades of technical experience with the design and implementation of other clinical trials and studies. Herein, we describe the key features of the study design, critical personnel and infrastructural elements, and key innovations. We will also briefly outline the systems engineering challenges entailed by this study. COMBAT is a randomized, placebo controlled, semi-blinded prospective Phase IIB clinical trial, conducted in a ground ambulance fleet based at a Level I trauma center, and part of a multicenter collaboration. The primary objective of COMBAT is to determine the efficacy of field resuscitation with plasma first, compared to standard of care (normal saline). To date we have enrolled 30 subjects in the COMBAT study. The ability to achieve intervention with a hemostatic resuscitation agent in the closest possible temporal proximity to injury is critical and represents an opportunity to forestall the evolution of the “bloody vicious cycle”. Thus, the COMBAT model for deploying plasma in first response units should serve as a model for RCTs of other hemostatic resuscitative agents. PMID:25784527

Efficacy of vitamin D3 supplementation in reducing incidence of pulmonary tuberculosis and mortality among HIV-infected Tanzanian adults initiating antiretroviral therapy: study protocol for a randomized controlled trial.

PubMed

Sudfeld, Christopher R; Mugusi, Ferdinand; Aboud, Said; Nagu, Tumaini J; Wang, Molin; Fawzi, Wafaie W

2017-02-10

HIV-infected adults initiating antiretroviral therapy (ART) in sub-Saharan Africa continue to experience high rates of morbidity and mortality during the initial months of treatment. Observational studies in high-income and resource-limited settings indicate that HIV-infected adults with low vitamin D levels may be at increased risk of mortality, HIV disease progression, and incidence of pulmonary tuberculosis (TB). As a result, vitamin D 3 supplementation may improve survival and treatment outcomes for HIV-infected adults initiating ART. The Trial of Vitamins-4 (ToV4) is an individually randomized, double-blind, placebo-controlled trial of vitamin D 3 (cholecalciferol) supplementation conducted among 4000 HIV-infected adults with low vitamin D levels [25-hydroxyvitamin D (25(OH)D) <30 ng/mL] initiating ART in Dar es Salaam, Tanzania. The two primary aims of the trial are to determine the effect of a vitamin D 3 supplementation regimen on incidence of (1) mortality and (2) pulmonary TB as compared to a matching placebo regimen. The primary safety outcome of the study is incident hypercalcemia. The investigational vitamin D 3 regimen consists of oral supplements containing 50,000 IU vitamin D 3 taken under direct observation at randomization and once a week for 3 weeks (four doses) followed by daily oral supplements containing 2000 IU vitamin D 3 taken at home from the fourth week until trial discharge at 1 year post ART initiation. Trial participants are followed up at weekly clinic visits during the first month of ART and at monthly clinic visits thereafter until trial discharge at 1 year post ART initiation. Secondary aims of the trial are to examine the effect of the vitamin D 3 regimen on CD4 T cell reconstitution, incidence of non-TB comorbidities, body mass index (BMI), depression and anxiety, physical activity, bone health, and immunologic biomarkers. The ToV4 will provide causal evidence on the effect of vitamin D 3 supplementation on incidence of pulmonary TB and mortality among HIV-infected Tanzanian adults initiating ART. The trial will also give insight to whether vitamin D 3 supplementation trials for the prevention of pulmonary TB should be pursued in HIV-uninfected populations. ClinicalTrials.gov, NCT01798680 . Registered on 21 February 2013.

Theory-based interventions for contraception.

PubMed

Lopez, Laureen M; Tolley, Elizabeth E; Grimes, David A; Chen-Mok, Mario

2009-01-21

The explicit use of theory in research helps expand the knowledge base. Theories and models have been used extensively in HIV-prevention research and in interventions for preventing sexually transmitted infections (STIs). The health behavior field uses many theories or models of change. However, educational interventions addressing contraception often have no stated theoretical base. Review randomized controlled trials that tested a theoretical approach to inform contraceptive choice; encourage contraceptive use; or promote adherence to, or continuation of, a contraceptive regimen. We searched computerized databases for trials that tested a theory-based intervention for improving contraceptive use (MEDLINE, POPLINE, CENTRAL, PsycINFO, EMBASE, ClinicalTrials.gov, and ICTRP). We also wrote to researchers to find other trials. Trials tested a theory-based intervention for improving contraceptive use. We excluded trials focused on high-risk groups. Interventions addressed the use of one or more contraceptive methods. The reports provided evidence that the intervention was based on a specific theory or model. The primary outcomes were pregnancy, contraceptive choice, initiating or changing contraceptive use, contraceptive regimen adherence, and contraception continuation. The primary author evaluated abstracts for eligibility. Two authors extracted data from included studies. We calculated the odds ratio for dichotomous outcomes and the mean difference for continuous data. No meta-analysis was conducted due to intervention differences. Of 26 trials, 12 interventions addressed contraception (other than condoms), while 14 focused on condom use for preventing HIV or STIs. In 2 of 10 trials with pregnancy or birth data, a theory-based group showed better results. Four of nine trials with contraceptive use (other than condoms) showed better outcomes in an experimental group. For condom use, a theory-based group had favorable results in 14 of 20 trials, but the number was halved in a subgroup analysis. Social Cognitive Theory was the main theoretical basis for 12 trials, and 10 showed positive results. Of the other 14 trials, favorable results were shown for other social cognition models (N=2), motivational interviewing (N=5), and the AIDS Risk Reduction Model (N=2). No major patterns were detected by type of theory, intervention, or target population. Family planning researchers and practitioners could apply the relevant theories and effective interventions from HIV and STI prevention. More thorough use of single theories would help inform the field about what works. Better reporting is needed on research design and intervention implementation.

NASA JSC water monitor system: City of Houston field demonstration

NASA Technical Reports Server (NTRS)

Taylor, R. E.; Jeffers, E. L.; Fricks, D. H.

1979-01-01

A water quality monitoring system with on-line and real time operation similar to the function in a spacecraft was investigated. A system with the capability to determine conformance to future high effluent quality standards and to increase the potential for reclamation and reuse of water was designed. Although all system capabilities were not verified in the initial field trial, fully automated operation over a sustained period with only routine manual adjustments was accomplished. Two major points were demonstrated: (1) the water monitor system has great potential in water monitoring and/or process control applications; and (2) the water monitor system represents a vast improvement over conventional (grab sample) water monitoring techniques.

A comparison of susceptibility to Myxobolus cerebralis among strains of rainbow trout and steelhead in field and laboratory trials

USGS Publications Warehouse

Densmore, Christine L.; Blazer, V.S.; Cartwright, Deborah D.; Schill, W.B.; Schachte, J.H.; Petrie, C.J.; Batur, M.V.; Waldrop, T.B.; Mack, A.; Pooler, P.S.

2001-01-01

Three strains of rainbow trout and steelhead Oncorhynchus mykiss were evaluated for the presence of whirling disease in field and laboratory trials. In the field exposures, fingerling Salmon River steelhead and Cayuga Lake and Randolph strains of rainbow trout were placed in wire cages in an earthen, stream-fed pond in New York State that was known to harbor Myxobolus cerebralis. Control fish were held at another hatchery that was free of whirling disease. In the controlled trials at the National Fish Health Research Laboratory, fingerling steelhead and Cayuga Lake and Mount Lassen rainbow trout were exposed to triactinomyxons at low (200 triactinomyxons/fish) or high (2,000 triactinomyxons/fish) levels for 2 h. Controls of each group were sham-exposed. Following an incubation period of 154 d for laboratory trials and 180 d for field trials, cranial tissue samples were taken for spore enumeration (field and laboratory trials) and histological analyses (laboratory only). Clinical signs of disease, including whirling behavior, blacktail, and skeletal deformities, were recorded for each fish in the laboratory trial at the terminal sampling. No clinical evidence of disease was noted among fish in the field trials. Clinical signs were noted among all strains in the laboratory trials at both exposure levels, and these signs were consistently greatest for the Mount Lassen strain. Whirling and skeletal deformities were more evident in the steelhead than in the Cayuga Lake rainbow trout; blacktail was more common in the Cayuga Lake fish. In both field and laboratory trials, spore counts were significantly higher for Cayuga Lake rainbow trout than in steelhead. In laboratory trials, moderate to marked cranial tissue lesions predominated in all three strains.

Mobile access to virtual randomization for investigator-initiated trials.

PubMed

Deserno, Thomas M; Keszei, András P

2017-08-01

Background/aims Randomization is indispensable in clinical trials in order to provide unbiased treatment allocation and a valid statistical inference. Improper handling of allocation lists can be avoided using central systems, for example, human-based services. However, central systems are unaffordable for investigator-initiated trials and might be inaccessible from some places, where study subjects need allocations. We propose mobile access to virtual randomization, where the randomization lists are non-existent and the appropriate allocation is computed on demand. Methods The core of the system architecture is an electronic data capture system or a clinical trial management system, which is extended by an R interface connecting the R server using the Java R Interface. Mobile devices communicate via the representational state transfer web services. Furthermore, a simple web-based setup allows configuring the appropriate statistics by non-statisticians. Our comprehensive R script supports simple randomization, restricted randomization using a random allocation rule, block randomization, and stratified randomization for un-blinded, single-blinded, and double-blinded trials. For each trial, the electronic data capture system or the clinical trial management system stores the randomization parameters and the subject assignments. Results Apps are provided for iOS and Android and subjects are randomized using smartphones. After logging onto the system, the user selects the trial and the subject, and the allocation number and treatment arm are displayed instantaneously and stored in the core system. So far, 156 subjects have been allocated from mobile devices serving five investigator-initiated trials. Conclusion Transforming pre-printed allocation lists into virtual ones ensures the correct conduct of trials and guarantees a strictly sequential processing in all trial sites. Covering 88% of all randomization models that are used in recent trials, virtual randomization becomes available for investigator-initiated trials and potentially for large multi-center trials.

Introduction to the Special Issue.

ERIC Educational Resources Information Center

Petrosino, Anthony

2003-01-01

Introduces the articles of this special issue focusing on randomized field trials in criminology. In spite of the overall lack of randomized field trials in criminology, some agencies and individuals are able to mount an impressive number of field trials, and these articles focus on their experiences. (SLD)

Advances in gene therapy for heart failure.

PubMed

Fish, Kenneth M; Ishikawa, Kiyotake

2015-04-01

Chronic heart failure is expected to increase its social and economic burden as a consequence of improved survival in patients with acute cardiac events. Cardiac gene therapy holds significant promise in heart failure treatment for patients with currently very limited or no treatment options. The introduction of adeno-associated virus (AAV) gene vector changed the paradigm of cardiac gene therapy, and now it is the primary vector of choice for chronic heart failure gene therapy in clinical and preclinical studies. Recently, there has been significant progress towards clinical translation in this field spearheaded by AAV-1 mediated sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) gene therapy targeting chronic advanced heart failure patients. Meanwhile, several independent laboratories are reporting successful gene therapy approaches in clinically relevant large animal models of heart failure and some of these approaches are expected to enter clinical trials in the near future. This review will focus on gene therapy approaches targeting heart failure that is in clinical trials and those close to its initial clinical trial application.

Errors in Postural Preparation Lead to Increased Choice Reaction Times for Step Initiation in Older Adults

PubMed Central

Nutt, John G.; Horak, Fay B.

2011-01-01

Background. This study asked whether older adults were more likely than younger adults to err in the initial direction of their anticipatory postural adjustment (APA) prior to a step (indicating a motor program error), whether initial motor program errors accounted for reaction time differences for step initiation, and whether initial motor program errors were linked to inhibitory failure. Methods. In a stepping task with choice reaction time and simple reaction time conditions, we measured forces under the feet to quantify APA onset and step latency and we used body kinematics to quantify forward movement of center of mass and length of first step. Results. Trials with APA errors were almost three times as common for older adults as for younger adults, and they were nine times more likely in choice reaction time trials than in simple reaction time trials. In trials with APA errors, step latency was delayed, correlation between APA onset and step latency was diminished, and forward motion of the center of mass prior to the step was increased. Participants with more APA errors tended to have worse Stroop interference scores, regardless of age. Conclusions. The results support the hypothesis that findings of slow choice reaction time step initiation in older adults are attributable to inclusion of trials with incorrect initial motor preparation and that these errors are caused by deficits in response inhibition. By extension, the results also suggest that mixing of trials with correct and incorrect initial motor preparation might explain apparent choice reaction time slowing with age in upper limb tasks. PMID:21498431

Combining auctions and performance-based payments in a forest enrichment field trial in Western Kenya.

PubMed

Khalumba, Mercelyne; Wünscher, Tobias; Wunder, Sven; Büdenbender, Mirjam; Holm-Müller, Karin

2014-06-01

Cost-effectiveness is an important aspect in the assessment of payments for environmental services (PES) initiatives. In participatory field trials with communities in Western Kenya, we combined procurement auctions for forest enrichment contracts with performance-based payments and compared the outcomes with a baseline scenario currently used by the Kenyan Forest Service. Procurement auctions were the most cost-effective. The competitive nature of the auction reduced contracting expenses (provision costs), and the result-oriented payments provided additional incentives to care for the planted seedlings, resulting in their improved survival rates (service quantity). These gains clearly exceeded increases in transaction costs associated with conducting an auction. The number of income-poor auction participants and winners was disproportionately high and local institutional buy-in was remarkably strong. Our participatory approach may, however, require adaptations when conducted at a larger scale. Although the number of contracts we monitored was limited and prohibited the use of statistical tests, our study is one of the first to reveal the benefits of using auctions for PES in developing countries. © 2014 Society for Conservation Biology.

Current Status of Gene Therapy for Inherited Lung Diseases

PubMed Central

Driskell, Ryan R.; Engelhardt, John F.

2007-01-01

Gene therapy as a treatment modality for pulmonary disorders has attracted significant interest over the past decade. Since the initiation of the first clinical trials for cystic fibrosis lung disease using recombinant adenovirus in the early 1990s, the field has encountered numerous obstacles including vector inflammation, inefficient delivery, and vector production. Despite these obstacles, enthusiasm for lung gene therapy remains high. In part, this enthusiasm is fueled through the diligence of numerous researchers whose studies continue to reveal great potential of new gene transfer vectors that demonstrate increased tropism for airway epithelia. Several newly identified serotypes of adeno-associated virus have demonstrated substantial promise in animal models and will likely surface soon in clinical trials. Furthermore, an increased understanding of vector biology has also led to the development of new technologies to enhance the efficiency and selectivity of gene delivery to the lung. Although the promise of gene therapy to the lung has yet to be realized, the recent concentrated efforts in the field that focus on the basic virology of vector development will undoubtedly reap great rewards over the next decade in treating lung diseases. PMID:12524461

Bone regeneration: stem cell therapies and clinical studies in orthopaedics and traumatology

PubMed Central

Gómez-Barrena, Enrique; Rosset, Philippe; Müller, Ingo; Giordano, Rosaria; Bunu, Carmen; Layrolle, Pierre; Konttinen, Yrjö T; Luyten, Frank P

2011-01-01

Abstract Regenerative medicine seeks to repair or replace damaged tissues or organs, with the goal to fully restore structure and function without the formation of scar tissue. Cell based therapies are promising new therapeutic approaches in regenerative medicine. By using mesenchymal stem cells, good results have been reported for bone engineering in a number of clinical studies, most of them investigator initiated trials with limited scope with respect to controls and outcome. With the implementation of a new regulatory framework for advanced therapeutic medicinal products, the stage is set to improve both the characterization of the cells and combination products, and pave the way for improved controlled and well-designed clinical trials. The incorporation of more personalized medicine approaches, including the use of biomarkers to identify the proper patients and the responders to treatment, will be contributing to progress in the field. Both translational and clinical research will move the boundaries in the field of regenerative medicine, and a coordinated effort will provide the clinical breakthroughs, particularly in the many applications of bone engineering. PMID:21251219

Advancing molecular-guided surgery through probe development and testing in a moderate cost evaluation pipeline

NASA Astrophysics Data System (ADS)

Pogue, Brian W.; Paulsen, Keith D.; Hull, Sally M.; Samkoe, Kimberley S.; Gunn, Jason; Hoopes, Jack; Roberts, David W.; Strong, Theresa V.; Draney, Daniel; Feldwisch, Joachim

2015-03-01

Molecular guided oncology surgery has the potential to transform the way decisions about resection are done, and can be critically important in areas such as neurosurgery where the margins of tumor relative to critical normal tissues are not readily apparent from visual or palpable guidance. Yet there are major financial barriers to advancing agents into clinical trials with commercial backing. We observe that development of these agents in the standard biological therapeutic paradigm is not viable, due to the high up front financial investment needed and the limitations in the revenue models of contrast agents for imaging. The hypothesized solution to this problem is to develop small molecular biologicals tagged with an established fluorescent reporter, through the chemical agent approval pathway, targeting a phase 0 trials initially, such that the initial startup phase can be completely funded by a single NIH grant. In this way, fast trials can be completed to de-risk the development pipeline, and advance the idea of fluorescence-guided surgery (FGS) reporters into human testing. As with biological therapies the potential successes of each agent are still moderate, but this process will allow the field to advance in a more stable and productive manner, rather than relying upon isolated molecules developed at high cost and risk. The pathway proposed and tested here uses peptide synthesis of an epidermal growth factor receptor (EGFR)-binding Affibody molecules, uniquely conjugated to IRDye 800CW, developed and tested in academic and industrial laboratories with well-established records for GMP production, fill and finish, toxicity testing, and early phase clinical trials with image guidance.

Randomised comparison of the effectiveness of the laryngeal mask airway supreme, i-gel and current practice in the initial airway management of prehospital cardiac arrest (REVIVE-Airways): a feasibility study research protocol

PubMed Central

Benger, Jonathan Richard; Voss, Sarah; Coates, David; Greenwood, Rosemary; Nolan, Jerry; Rawstorne, Steven; Rhys, Megan; Thomas, Matthew

2013-01-01

Introduction Effective cardiopulmonary resuscitation with appropriate airway management improves outcomes following out-of-hospital cardiac arrest (OHCA). Historically, tracheal intubation has been accepted as the optimal form of OHCA airway management in the UK. The Joint Royal Colleges Ambulance Liaison Committee recently concluded that newer supraglottic airway devices (SADs) are safe and effective devices for hospital procedures and that their use in OHCA should be investigated. This study will address an identified gap in current knowledge by assessing whether it is feasible to use a cluster randomised design to compare SADs with current practice, and also to each other, during OHCA. Methods and analysis The primary objective of this study is to assess the feasibility of a cluster randomised trial to compare the ventilation success of two newer SADs: the i-gel and the laryngeal mask airway supreme to usual practice during the initial airway management of OHCA. The secondary objectives are to collect data on ventilation success, further airway interventions required, loss of a previously established airway during transport, airway management on arrival at hospital (or termination of the resuscitation attempt), initial resuscitation success, survival to intensive care admission, survival to hospital discharge and patient outcome at 3 months. Ambulance paramedics will be randomly allocated to one of the three methods of airway management. Adults in medical OHCA attended by a trial paramedic will be eligible for the study. Ethics and dissemination Approval for the study has been obtained from a National Health Service Research Ethics Committee with authority to review proposals for trials of a medical device in incapacitated adults. The results will be made publicly available on an open access website, and we will publish the findings in appropriate journals and present them at national and international conferences relevant to the subject field. Trial registration ISRCTN: 18528625. PMID:23408081

A trial of ignition innovation of gasoline engine by nanosecond pulsed low temperature plasma ignition

NASA Astrophysics Data System (ADS)

Shiraishi, Taisuke; Urushihara, Tomonori; Gundersen, Martin

2009-07-01

Application of nanosecond pulsed low temperature plasma as an ignition technique for automotive gasoline engines, which require a discharge under conditions of high back pressure, has been studied experimentally using a single-cylinder engine. The nanosecond pulsed plasma refers to the transient (non-equilibrated) phase of a plasma before the formation of an arc discharge; it was obtained by applying a high voltage with a nanosecond pulse (FWHM of approximately 80 or 25 ns) between coaxial cylindrical electrodes. It was confirmed that nanosecond pulsed plasma can form a volumetric multi-channel streamer discharge at an energy consumption of 60 mJ cycle-1 under a high back pressure of 1400 kPa. It was found that the initial combustion period was shortened compared with the conventional spark ignition. The initial flame visualization suggested that the nanosecond pulsed plasma ignition results in the formation of a spatially dispersed initial flame kernel at a position of high electric field strength around the central electrode. It was observed that the electric field strength in the air gap between the coaxial cylindrical electrodes was increased further by applying a shorter pulse. It was also clarified that the shorter pulse improved ignitability even further.

Influence of Weather on the Predicted Moisture Content of Field Chopped EnergySorghum and Switchgrass

DOE PAGES

Popp, Michael P.; Searcy, Stephen S.; Sokhansanj, Shahab; ...

2015-03-25

To determine the effects of weather on harvested moisture content (MC) of switchgrass (Panicum virgatum) and energy sorghum (Sorghum bicolor), tracking of harvest progress on individual fields in the Integrated Biomass Supply and Logistics (IBSAL) model was modified to allow: i) rewetting of swathed material in the drying formulae; and ii) field queuing rules based on equipment availability and weather. Estimated crop yield and initial MC by harvest date, as observed in field trials, along with the modeling of different delays between mowing and harvest allowed estimation of harvested MC, annual tonnage processed and associated processing cost differences by cropmore » and location over 10 years. Extending the hours of annual equipment use had minor implications on cost of production. Energy sorghum proved difficult to dry in the field. Its higher yield, leading to shorter supply distance to the plant, may justify harvesting of energy sorghum early in the season with drier weather. Lastly, later harvest for lower-yielding switchgrass offers MC advantages.« less

Influence of Weather on the Predicted Moisture Content of Field Chopped EnergySorghum and Switchgrass

DOE Office of Scientific and Technical Information (OSTI.GOV)

Popp, Michael P.; Searcy, Stephen S.; Sokhansanj, Shahab

To determine the effects of weather on harvested moisture content (MC) of switchgrass (Panicum virgatum) and energy sorghum (Sorghum bicolor), tracking of harvest progress on individual fields in the Integrated Biomass Supply and Logistics (IBSAL) model was modified to allow: i) rewetting of swathed material in the drying formulae; and ii) field queuing rules based on equipment availability and weather. Estimated crop yield and initial MC by harvest date, as observed in field trials, along with the modeling of different delays between mowing and harvest allowed estimation of harvested MC, annual tonnage processed and associated processing cost differences by cropmore » and location over 10 years. Extending the hours of annual equipment use had minor implications on cost of production. Energy sorghum proved difficult to dry in the field. Its higher yield, leading to shorter supply distance to the plant, may justify harvesting of energy sorghum early in the season with drier weather. Lastly, later harvest for lower-yielding switchgrass offers MC advantages.« less

Evaluating Research and Impact: A Bibliometric Analysis of Research by the NIH/NIAID HIV/AIDS Clinical Trials Networks

PubMed Central

Rosas, Scott R.; Kagan, Jonathan M.; Schouten, Jeffrey T.; Slack, Perry A.; Trochim, William M. K.

2011-01-01

Evaluative bibliometrics uses advanced techniques to assess the impact of scholarly work in the context of other scientific work and usually compares the relative scientific contributions of research groups or institutions. Using publications from the National Institute of Allergy and Infectious Diseases (NIAID) HIV/AIDS extramural clinical trials networks, we assessed the presence, performance, and impact of papers published in 2006–2008. Through this approach, we sought to expand traditional bibliometric analyses beyond citation counts to include normative comparisons across journals and fields, visualization of co-authorship across the networks, and assess the inclusion of publications in reviews and syntheses. Specifically, we examined the research output of the networks in terms of the a) presence of papers in the scientific journal hierarchy ranked on the basis of journal influence measures, b) performance of publications on traditional bibliometric measures, and c) impact of publications in comparisons with similar publications worldwide, adjusted for journals and fields. We also examined collaboration and interdisciplinarity across the initiative, through network analysis and modeling of co-authorship patterns. Finally, we explored the uptake of network produced publications in research reviews and syntheses. Overall, the results suggest the networks are producing highly recognized work, engaging in extensive interdisciplinary collaborations, and having an impact across several areas of HIV-related science. The strengths and limitations of the approach for evaluation and monitoring research initiatives are discussed. PMID:21394198

The Plant Alkaloid Camptothecin as a Novel Antifouling Compound for Marine Paints: Laboratory Bioassays and Field Trials.

PubMed

Feng, Dan Qing; He, Jian; Chen, Si Yu; Su, Pei; Ke, Cai Huan; Wang, Wei

2018-06-02

The extensive use of copper and booster biocides in antifouling (AF) paints has raised environmental concerns and the need to develop new AF agents. In the present study, 18 alkaloids derived from terrestrial plants were initially evaluated for AF activity using laboratory bioassays with the bryozoan Bugula neritina and the barnacle Balanus albicostatus. The results showed that 4 of the 18 alkaloids were effective in inhibiting larval settlement of B. neritina, with an EC 50 range of 6.18 to 43.11 μM, and 15 of the 18 alkaloids inhibited larval settlement of B. albicostatus, with EC 50 values ranging from 1.18 to 67.58 μM. Field trials that incorporated five alkaloids respectively into paints with 20% w/w indicated an in situ AF efficiency of evodiamine, strychnine, camptothecin (CPT), and cepharanthine, with the most potent compound being CPT, which also exhibited stronger AF efficiency than the commercial antifoulants cuprous oxide and zinc pyrithione in the field over a period of 12 months. Further field trials with different CPT concentrations (0.1 to 20% w/w) in the paints suggested a concentration-dependent AF performance in the natural environment, and the effective concentrations to significantly inhibit settlement of biofoulers in the field were ≥ 0.5% w/w (the efficiency of 0.5% w/w lasted for 2 months). Moreover, CPT toxicity against the crustacean Artemia salina, the planktonic microalgae Phaeodactylum tricornutum and Isochrysis galbana, was examined. The results showed that 24 h LC 50 of CPT against A. salina was 20.75 μM, and 96 h EC 50 (growth inhibition) values of CPT to P. tricornutum and I. galbana were 55.81 and 6.29 μM, respectively, indicating that CPT was comparatively less toxic than several commercial antifoulants previously reported. Our results suggest the novel potential application of CPT as an antifoulant.

Establishment and maintenance of asepsis in endodontics - a review of the literature.

PubMed

Malmberg, Leona; Björkner, Annika Elisabeth; Bergenholtz, Gunnar

2016-08-01

Successful endodontic treatment depends on effective measures to eliminate and prevent infection of root canals. Initially treatment should start with isolation and disinfection of the operating field. This review makes an inventory of the available knowledge regarding its establishment and maintenance. A literature search was conducted in the PubMed database in order to identify clinical trials examining disinfection or unintentional contamination of the endodontic operative field. A list of 115 articles was obtained and screened. Five relevant articles were identified. These articles were read in full text. The reference lists from these articles were checked manually for additional studies and three studies were obtained. A total of eight articles met the inclusion criteria. There was a great variety in terms of aim, method, and material of the included studies. None could prove a totally reliable aseptic operative field and not one chemical, or combination of chemicals, were found in more than one study. No study documented complete asepsis following initial disinfection, and no study could document predictable maintenance of an established bacteria-free surface. Critical appraisal and standardization of the disinfection and aseptic procedures in endodontics are needed.

Stem cell clinical trials for spinal cord injury: readiness, reluctance, redefinition.

PubMed

Illes, J; Reimer, J C; Kwon, B K

2011-11-01

A wealth of scientific and clinical research has focused on the use of stem cells as a potential therapy for spinal cord injury (SCI), culminating most recently in the initiation of clinical trials. However, with the urgency that scientists and clinicians have undertaken to move forward with novel therapies for this devastating injury, the perspectives of stakeholders who live with a SCI have been left behind. Translational research in this rapidly growing field therefore overlooks a critically important viewpoint. We address this concern with a qualitative study of the perspectives on experimental stem cell treatments from individuals who have actually suffered a spinal cord injury. Using focus groups and interviews, we engaged individuals with thoracic and cervical SCIs at sub-acute and chronic stages post-injury. We found four major themes that inform the progression of stem cell research to clinical trials: 'readiness', 'the here and now', 'wait and see', and 'informed hope'. Taken together, the data suggest a profound difference related to target timing of stem cell clinical trials and the perspectives about timing from those who are the end-beneficiaries of therapy. To bridge this gap, we conclude with a number of considerations for the timing disparity of trials and recommendations for improving informed consent.

Understanding and preventing type 1 diabetes through the unique working model of TrialNet.

PubMed

Battaglia, Manuela; Anderson, Mark S; Buckner, Jane H; Geyer, Susan M; Gottlieb, Peter A; Kay, Thomas W H; Lernmark, Åke; Muller, Sarah; Pugliese, Alberto; Roep, Bart O; Greenbaum, Carla J; Peakman, Mark

2017-11-01

Type 1 diabetes is an autoimmune disease arising from the destruction of pancreatic insulin-producing beta cells. The disease represents a continuum, progressing sequentially at variable rates through identifiable stages prior to the onset of symptoms, through diagnosis and into the critical periods that follow, culminating in a variable depth of beta cell depletion. The ability to identify the very earliest of these presymptomatic stages has provided a setting in which prevention strategies can be trialled, as well as furnishing an unprecedented opportunity to study disease evolution, including intrinsic and extrinsic initiators and drivers. This niche opportunity is occupied by Type 1 Diabetes TrialNet, an international consortium of clinical trial centres that leads the field in intervention and prevention studies, accompanied by deep longitudinal bio-sampling. In this review, we focus on discoveries arising from this unique bioresource, comprising more than 70,000 samples, and outline the processes and science that have led to new biomarkers and mechanistic insights, as well as identifying new challenges and opportunities. We conclude that via integration of clinical trials and mechanistic studies, drawing in clinicians and scientists and developing partnership with industry, TrialNet embodies an enviable and unique working model for understanding a disease that to date has no cure and for designing new therapeutic approaches.

Understanding and preventing type 1 diabetes through the unique working model of TrialNet

PubMed Central

Anderson, Mark S.; Buckner, Jane H.; Geyer, Susan M.; Gottlieb, Peter A.; Kay, Thomas W. H.; Lernmark, Åke; Muller, Sarah; Pugliese, Alberto; Roep, Bart O.; Greenbaum, Carla J.

2018-01-01

Type 1 diabetes is an autoimmune disease arising from the destruction of pancreatic insulin-producing beta cells. The disease represents a continuum, progressing sequentially at variable rates through identifiable stages prior to the onset of symptoms, through diagnosis and into the critical periods that follow, culminating in a variable depth of beta cell depletion. The ability to identify the very earliest of these presymptomatic stages has provided a setting in which prevention strategies can be trialled, as well as furnishing an unprecedented opportunity to study disease evolution, including intrinsic and extrinsic initiators and drivers. This niche opportunity is occupied by Type 1 Diabetes TrialNet, an international consortium of clinical trial centres that leads the field in intervention and prevention studies, accompanied by deep longitudinal bio-sampling. In this review, we focus on discoveries arising from this unique bioresource, comprising more than 70,000 samples, and outline the processes and science that have led to new biomarkers and mechanistic insights, as well as identifying new challenges and opportunities. We conclude that via integration of clinical trials and mechanistic studies, drawing in clinicians and scientists and developing partnership with industry, TrialNet embodies an enviable and unique working model for understanding a disease that to date has no cure and for designing new therapeutic approaches. PMID:28770323

'It looks like you just want them when things get rough': civil society perspectives on negative trial results and stakeholder engagement in HIV prevention trials.

PubMed

Koen, Jennifer; Essack, Zaynab; Slack, Catherine; Lindegger, Graham; Newman, Peter A

2013-12-01

Civil society organizations (CSOs) have significantly impacted on the politics of health research and the field of bioethics. In the global HIV epidemic, CSOs have served a pivotal stakeholder role. The dire need for development of new prevention technologies has raised critical challenges for the ethical engagement of community stakeholders in HIV research. This study explored the perspectives of CSO representatives involved in HIV prevention trials (HPTs) on the impact of premature trial closures on stakeholder engagement. Fourteen respondents from South African and international CSOs representing activist and advocacy groups, community mobilisation initiatives, and human and legal rights groups were purposively sampled based on involvement in HPTs. Interviews were conducted from February-May 2010. Descriptive analysis was undertaken across interviews and key themes were developed inductively. CSO representatives largely described positive outcomes of recent microbicide and HIV vaccine trial terminations, particularly in South Africa, which they attributed to improvements in stakeholder engagement. Ongoing challenges to community engagement included the need for principled justifications for selective stakeholder engagement at strategic time-points, as well as the need for legitimate alternatives to CABs as mechanisms for engagement. Key issues for CSOs in relation to research were also raised. © 2012 John Wiley & Sons Ltd.

Evaluation of early efficacy endpoints for proof-of-concept trials.

PubMed

Chen, Cong; Sun, Linda; Li, Chih-Lin

2013-03-11

A Phase II proof-of-concept (POC) trial usually uses an early efficacy endpoint other than a clinical endpoint as the primary endpoint. Because of the advancement in bioscience and technology, which has yielded a number of new surrogate biomarkers, drug developers often have more candidate endpoints to choose from than they can handle. As a result, selection of endpoint and its effect size as well as choice of type I/II error rates are often at the center of heated debates in design of POC trials. While optimization of the trade-off between benefit and cost is the implicit objective in such a decision-making process, it is seldom explicitly accounted for in practice. In this research note, motivated by real examples from the oncology field, we provide practical measures for evaluation of early efficacy endpoints (E4) for POC trials. We further provide optimal design strategies for POC trials that include optimal Go-No Go decision criteria for initiation of Phase III and optimal resource allocation strategies for conducting multiple POC trials in a portfolio under fixed resources. Although oncology is used for illustration purpose, the same idea developed in this research note also applies to similar situations in other therapeutic areas or in early-stage drug development in that a Go-No Go decision has to rely on limited data from an early efficacy endpoint and cost-effectiveness is the main concern.

Ghost Authorship in Industry-Initiated Randomised Trials

PubMed Central

Gøtzsche, Peter C; Hróbjartsson, Asbjørn; Johansen, Helle Krogh; Haahr, Mette T; Altman, Douglas G; Chan, An-Wen

2007-01-01

Background Ghost authorship, the failure to name, as an author, an individual who has made substantial contributions to an article, may result in lack of accountability. The prevalence and nature of ghost authorship in industry-initiated randomised trials is not known. Methods and Findings We conducted a cohort study comparing protocols and corresponding publications for industry-initiated trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg in 1994–1995. We defined ghost authorship as present if individuals who wrote the trial protocol, performed the statistical analyses, or wrote the manuscript, were not listed as authors of the publication, or as members of a study group or writing committee, or in an acknowledgment. We identified 44 industry-initiated trials. We did not find any trial protocol or publication that stated explicitly that the clinical study report or the manuscript was to be written or was written by the clinical investigators, and none of the protocols stated that clinical investigators were to be involved with data analysis. We found evidence of ghost authorship for 33 trials (75%; 95% confidence interval 60%–87%). The prevalence of ghost authorship was increased to 91% (40 of 44 articles; 95% confidence interval 78%–98%) when we included cases where a person qualifying for authorship was acknowledged rather than appearing as an author. In 31 trials, the ghost authors we identified were statisticians. It is likely that we have overlooked some ghost authors, as we had very limited information to identify the possible omission of other individuals who would have qualified as authors. Conclusions Ghost authorship in industry-initiated trials is very common. Its prevalence could be considerably reduced, and transparency improved, if existing guidelines were followed, and if protocols were publicly available. PMID:17227134

Ghost authorship in industry-initiated randomised trials.

PubMed

Gøtzsche, Peter C; Hróbjartsson, Asbjørn; Johansen, Helle Krogh; Haahr, Mette T; Altman, Douglas G; Chan, An-Wen

2007-01-01

Ghost authorship, the failure to name, as an author, an individual who has made substantial contributions to an article, may result in lack of accountability. The prevalence and nature of ghost authorship in industry-initiated randomised trials is not known. We conducted a cohort study comparing protocols and corresponding publications for industry-initiated trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg in 1994-1995. We defined ghost authorship as present if individuals who wrote the trial protocol, performed the statistical analyses, or wrote the manuscript, were not listed as authors of the publication, or as members of a study group or writing committee, or in an acknowledgment. We identified 44 industry-initiated trials. We did not find any trial protocol or publication that stated explicitly that the clinical study report or the manuscript was to be written or was written by the clinical investigators, and none of the protocols stated that clinical investigators were to be involved with data analysis. We found evidence of ghost authorship for 33 trials (75%; 95% confidence interval 60%-87%). The prevalence of ghost authorship was increased to 91% (40 of 44 articles; 95% confidence interval 78%-98%) when we included cases where a person qualifying for authorship was acknowledged rather than appearing as an author. In 31 trials, the ghost authors we identified were statisticians. It is likely that we have overlooked some ghost authors, as we had very limited information to identify the possible omission of other individuals who would have qualified as authors. Ghost authorship in industry-initiated trials is very common. Its prevalence could be considerably reduced, and transparency improved, if existing guidelines were followed, and if protocols were publicly available.

The Styx field trial

PubMed Central

Gemmell, M. A.

1968-01-01

An assessment was made of the effectiveness of the generally accepted methods recommended for controlling hydatid disease during the course of a field-trial, initiated in 1943 in an isolated region of New Zealand. The results obtained during the first 21 years are described. Basically, the trial was an attempt to compare the effectiveness of a general public health educational programme and an anthelmintic programme using arecoline hydrobromide for treatment of dogs with that of a specific educational programme using this compound as a diagnostic agent. Arecoline hydrobromide was found to be too uncertain in its action to be of practical value as an anthelmintic. The development of diagnostic techniques, described in this paper, made it possible to use the compound for diagnostic purposes and thus for educational purposes, since each dog could be examined for tapeworms in the presence of the owner. Using changes in the annual prevalence rate in sheep of the cysts of E. granulosus and those of T. hydatigena as the principal indicators, the conclusion has been reached that the specific diagnostic approach achieved more success than the general educational and treatment programme. The principal reason for this appears to be that the former approach induced a greater awareness in owners of the need for strict management to prevent dogs gaining access to infective raw offal than that stimulated in the community when the dogs were dosed but not examined. ImagesFIG. 2FIG. 4FIG. 5 PMID:5303843

Oncolytic Virus Therapy of Glioblastoma Multiforme – Concepts and Candidates

PubMed Central

Wollmann, Guido; Ozduman, Koray; van den Pol, Anthony N.

2012-01-01

Twenty years of oncolytic virus (OV) development have created a field that is driven by the potential promise of lasting impact on our cancer treatment repertoire. With the field constantly expanding – over 20 viruses have been recognized as potential OVs – new virus candidates continue to emerge even as established viruses reach clinical trials. They all share the defining commonalities of selective replication in tumors, subsequent tumor cell lysis, and dispersion within the tumor. Members from diverse virus classes with distinctly different biologies and host species have been identified. Of these viruses, 15 have been tested on human glioblastoma multiforme (GBM). So far, 20 clinical trials have been conducted or initiated using attenuated strains of 7 different oncolytic viruses against GBM. In this review, we present an overview of viruses that have been developed or considered for GBM treatment. We outline the principles of tumor targeting and selective viral replication, which include mechanisms of tumor-selective binding, and molecular elements usurping cellular biosynthetic machinery in transformed cells. Results from clinical trials have clearly established the proof of concept and have confirmed the general safety of OV application in the brain. The moderate clinical efficacy has not yet matched the promising preclinical lab results; next-generation OVs that are either “armed” with therapeutic genes or that are embedded in a multimodality treatment regimen should enhance the clinical results. PMID:22290260

Design of the PRINCESS trial: pre-hospital resuscitation intra-nasal cooling effectiveness survival study (PRINCESS).

PubMed

Nordberg, Per; Taccone, Fabio Silvio; Castren, Maaret; Truhlár, Anatolij; Desruelles, Didier; Forsberg, Sune; Hollenberg, Jacob; Vincent, Jean-Louis; Svensoon, Leif

2013-11-25

Therapeutic hypothermia (TH, 32-34°C) has been shown to improve neurological outcome in comatose survivors of out-of-hospital cardiac arrest (OHCA) with ventricular tachycardia or fibrillation. Earlier initiation of TH may increase the beneficial effects. Experimental studies have suggested that starting TH during cardiopulmonary resuscitation (CPR) may further enhance its neuroprotective effects. The aim of this study was to evaluate whether intra-arrest TH (IATH), initiated in the field with trans nasal evaporative cooling (TNEC), would provide outcome benefits when compared to standard of care in patients being resuscitated from OHCA. We describe the methodology of a multi-centre, randomized, controlled trial comparing IATH delivered through TNEC device (Rhinochill, Benechill Inc., San Diego, CA, USA) during CPR to standard treatment, including TH initiated after hospital admission. The primary outcome is neurological intact survival defined as cerebral performance category 1-2 at 90 days among those patients who are admitted to the hospital. Secondary outcomes include survival at 90 days, proportion of patients achieving a return to spontaneous circulation (ROSC), the proportion of patients admitted alive to the hospital and the proportion of patients achieving target temperature (<34°C) within the first 4 hours since CA. This ongoing trial will assess the impact of IATH with TNEC, which may be able to rapidly induce brain cooling and have fewer side effects than other methods, such as cold fluid infusion. If this intervention is found to improve neurological outcome, its early use in the pre-hospital setting will be considered as an early neuro-protective strategy in OHCA. NCT01400373.

Timing of Radiation Therapy and Chemotherapy After Breast-Conserving Surgery for Node-Positive Breast Cancer: Long-Term Results From International Breast Cancer Study Group Trials VI and VII

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karlsson, Per, E-mail: per.karlsson@oncology.gu.se; Cole, Bernard F.; Price, Karen N.

Purpose: To update the previous report from 2 randomized clinical trials, now with a median follow-up of 16 years, to analyze the effect of radiation therapy timing on local failure and disease-free survival. Patients and Methods: From July 1986 to April 1993, International Breast Cancer Study Group trial VI randomly assigned 1475 pre-/perimenopausal women with node-positive breast cancer to receive 3 or 6 cycles of initial chemotherapy (CT). International Breast Cancer Study Group trial VII randomly assigned 1212 postmenopausal women with node-positive breast cancer to receive tamoxifen for 5 years, or tamoxifen for 5 years with 3 early cycles of initial CT. Formore » patients who received breast-conserving surgery (BCS), radiation therapy (RT) was delayed until initial CT was completed; 4 or 7 months after BCS for trial VI and 2 or 4 months for trial VII. We compared RT timing groups among 433 patients on trial VI and 285 patients on trial VII who received BCS plus RT. Endpoints were local failure, regional/distant failure, and disease-free survival (DFS). Results: Among pre-/perimenopausal patients there were no significant differences in disease-related outcomes. The 15-year DFS was 48.2% in the group allocated 3 months initial CT and 44.9% in the group allocated 6 months initial CT (hazard ratio [HR] 1.12; 95% confidence interval [CI] 0.87-1.45). Among postmenopausal patients, the 15-year DFS was 46.1% in the no-initial-CT group and 43.3% in the group allocated 3 months initial CT (HR 1.11; 95% CI 0.82-1.51). Corresponding HRs for local failures were 0.94 (95% CI 0.61-1.46) in trial VI and 1.51 (95% CI 0.77-2.97) in trial VII. For regional/distant failures, the respective HRs were 1.15 (95% CI 0.80-1.63) and 1.08 (95% CI 0.69-1.68). Conclusions: This study confirms that, after more than 15 years of follow-up, it is reasonable to delay radiation therapy until after the completion of standard CT.« less

Making randomised trials more efficient: report of the first meeting to discuss the Trial Forge platform.

PubMed

Treweek, Shaun; Altman, Doug G; Bower, Peter; Campbell, Marion; Chalmers, Iain; Cotton, Seonaidh; Craig, Peter; Crosby, David; Davidson, Peter; Devane, Declan; Duley, Lelia; Dunn, Janet; Elbourne, Diana; Farrell, Barbara; Gamble, Carrol; Gillies, Katie; Hood, Kerry; Lang, Trudie; Littleford, Roberta; Loudon, Kirsty; McDonald, Alison; McPherson, Gladys; Nelson, Annmarie; Norrie, John; Ramsay, Craig; Sandercock, Peter; Shanahan, Daniel R; Summerskill, William; Sydes, Matt; Williamson, Paula; Clarke, Mike

2015-06-05

Randomised trials are at the heart of evidence-based healthcare, but the methods and infrastructure for conducting these sometimes complex studies are largely evidence free. Trial Forge ( www.trialforge.org ) is an initiative that aims to increase the evidence base for trial decision making and, in doing so, to improve trial efficiency.This paper summarises a one-day workshop held in Edinburgh on 10 July 2014 to discuss Trial Forge and how to advance this initiative. We first outline the problem of inefficiency in randomised trials and go on to describe Trial Forge. We present participants' views on the processes in the life of a randomised trial that should be covered by Trial Forge.General support existed at the workshop for the Trial Forge approach to increase the evidence base for making randomised trial decisions and for improving trial efficiency. Agreed upon key processes included choosing the right research question; logistical planning for delivery, training of staff, recruitment, and retention; data management and dissemination; and close down. The process of linking to existing initiatives where possible was considered crucial. Trial Forge will not be a guideline or a checklist but a 'go to' website for research on randomised trials methods, with a linked programme of applied methodology research, coupled to an effective evidence-dissemination process. Moreover, it will support an informal network of interested trialists who meet virtually (online) and occasionally in person to build capacity and knowledge in the design and conduct of efficient randomised trials.Some of the resources invested in randomised trials are wasted because of limited evidence upon which to base many aspects of design, conduct, analysis, and reporting of clinical trials. Trial Forge will help to address this lack of evidence.

Assessment of Safety and Effectiveness of the Extracorporeal Continuous-Flow Ventricular Assist Device (BR16010) Use as a Bridge-to-Decision Therapy for Severe Heart Failure or Refractory Cardiogenic Shock: Study Protocol for Single-Arm Non-randomized, Uncontrolled, and Investigator-Initiated Clinical Trial.

PubMed

Fukushima, Norihide; Tatsumi, Eisuke; Seguchi, Osamu; Takewa, Yoshiaki; Hamasaki, Toshimitsu; Onda, Kaori; Yamamoto, Haruko; Hayashi, Teruyuki; Fujita, Tomoyuki; Kobayashi, Junjiro

2018-06-08

The management of heart failure patients presenting in a moribund state remains challenging, despite significant advances in the field of ventricular assist systems. Bridge to decision involves using temporary devices to stabilize the hemodynamic state of such patients while further assessment is performed and a decision can be made regarding patient management. The purpose of this study (NCVC-BTD_01, National Cerebral and Cardiovascular Center-Bridge to Dicision_01) is to assess the safety and effectiveness of the newly developed extracorporeal continuous-flow ventricular assist system employing a disposable centrifugal pump with a hydrodynamically levitated bearing (BR16010) use as a bridge-to-decision therapy for patients with severe heart failure or refractory cardiogenic shock. NCVC-BTD_01 is a single-center, single-arm, open-label, exploratory, medical device, investigator-initiated clinical study. It is conducted at the National Cerebral and Cardiovascular Center in Japan. A total of nine patients will be enrolled in the study. The study was planned using Simon's minimax two-stage phase design. The primary endpoint is a composite of survival free of device-related serious adverse events and complications during device support. For left ventricular assistance, withdrawal of a trial device due to cardiac function recovery or exchange to other ventricular assist devices (VADs) for the purpose of bridge to transplantation (BTT) during 30 days after implantation will be considered study successes. For right ventricular assistance, withdrawal of tal device due to right ventricular function recovery within 30 days after implantation will be considered a study success. Secondary objectives include changes in brain natriuretic peptide levels (7 days after implantation of a trial device and the day of withdrawal of a trial device), period of mechanical ventricular support, changes in left ventricular ejection fraction (7 days after implantation of a trial device and the day of withdrawal of a trial device), and changes in left ventricular diastolic dimension (7 days after implantation of a trial device and the day of withdrawal of a trial device). We will disseminate the findings through regional, national, and international conferences and through peer-reviewed journals. UMIN Clinical Trials Registry (UMIN-CTR; R000033243) registered on 8 September 2017.

Partnerships and Pathways of Dissemination: The NIDA-SAMHSA Blending Initiative in the Clinical Trials Network

PubMed Central

Martino, Steve; Brigham, Gregory S.; Higgins, Christine; Gallon, Steve; Freese, Thomas E.; Albright, Lonnetta M.; Hulsey, Eric G.; Krom, Laurie; Storti, Susan A.; Perl, Harold; Nugent, Cathrine D.; Pintello, Denise; Condon, Timothy P.

2010-01-01

Since 2001, the National Drug Abuse Treatment Clinical Trials Network (CTN) has worked to put the results of its trials into the hands of community treatment programs, in large part through its participation in the National Institute on Drug Abuse - Substance Abuse and Mental Health Services Administration Blending Initiative and its close involvement with the Center for Substance Abuse Treatment’s Addiction Technology Transfer Centers. This article describes 1) the CTN’s integral role in the Blending Initiative, 2) key partnerships and dissemination pathways through which the results of CTN trials are developed into blending products and then transferred to community treatment programs, and 3) three blending initiatives involving buprenorphine, motivational incentives, and motivational interviewing. The Blending Initiative has resulted in high utilization of its products, preparation of over 200 regional trainers, widespread training of service providers in most U.S. States, Puerto Rico, and the U.S. Virgin Islands, and movement toward the development of web-based implementation supports and technical assistance. Implications for future directions of the Blending Initiative and opportunities for research are discussed. PMID:20307793

An overview of the information management component of RICIS

NASA Technical Reports Server (NTRS)

Bishop, Peter C.

1987-01-01

Information management is the RICIS (Research Institute for Computing and Information Systems) research area which covers four types of tasks initiated during the first year of research: (1) surveys - a description of the existing state of some area in computing and information systems; (2) forecasts - a description of the alternative future states of some area; (3) plans - an approach to accomplishing some objective in the future; and (4) demonstrations - working prototypes and field trials to study the feasibility and the benefits of a particular information system. The activity in these research areas is described.

The ethics of human gene transfer.

PubMed

Kimmelman, Jonathan

2008-03-01

Almost 20 years since the first gene-transfer trial was carried out in humans, the field has made significant advances towards clinical application. Nevertheless, it continues to face numerous unresolved ethical challenges--among them are the question of when to initiate human testing, the acceptability of germline modification and whether the technique should be applied to the enhancement of traits. Although such issues have precedents in other medical contexts, they take on a different character in gene transfer, in part because of the scientific uncertainty and the social context of innovation.

Gene Therapy in Fanconi Anemia: A Matter of Time, Safety and Gene Transfer Tool Efficiency.

PubMed

Verhoeyen, Els; Roman-Rodriguez, Francisco Jose; Cosset, Francois-Loic; Levy, Camille; Rio, Paula

2017-01-01

Fanconi anemia (FA) is a rare genetic syndrome characterized by progressive marrow failure. Gene therapy by infusion of FA-corrected autologous hematopoietic stem cells (HSCs) may offer a potential cure since it is a monogenetic disease with mutations in the FANC genes, coding for DNA repair enzymes [1]. However, the collection of hCD34+-cells in FA patients implies particular challenges because of the reduced numbers of progenitor cells present in their bone marrow (BM) [2] or mobilized peripheral blood [3-5]. In addition, the FA genetic defect fragilizes the HSCs [6]. These particular features might explain why the first clinical trials using murine leukemia virus derived retroviral vectors conducted for FA failed to show engraftment of corrected cells. The gene therapy field is now moving towards the use of lentiviral vectors (LVs) evidenced by recent succesful clinical trials for the treatment of patients suffering from adrenoleukodystrophy (ALD) [7], β-thalassemia [8], metachromatic leukodystrophy [9] and Wiskott-Aldrich syndrome [10]. LV trials for X-linked severe combined immunodificiency and Fanconi anemia (FA) defects were recently initiated [11, 12]. Fifteen years of preclinical studies using different FA mouse models and in vitro research allowed us to find the weak points in the in vitro culture and transduction conditions, which most probably led to the initial failure of FA HSC gene therapy. In this review, we will focus on the different obstacles, unique to FA gene therapy, and how they have been overcome through the development of optimized protocols for FA HSC culture and transduction and the engineering of new gene transfer tools for FA HSCs. These combined advances in the field hopefully will allow the correction of the FA hematological defect in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

76 FR 48119 - Oral Rabies Vaccine Trial; Availability of a Risk Assessment and an Environmental Assessment

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-08

...] Oral Rabies Vaccine Trial; Availability of a Risk Assessment and an Environmental Assessment AGENCY... environmental assessment relative to an oral rabies vaccination field trial in West Virginia. The environmental... rabies vaccine, analyzes the use of that vaccine in field safety and efficacy trials in West Virginia...

Early initiation of beta blockade in heart failure: issues and evidence.

PubMed

Williams, Randall E

2005-09-01

Despite clinical trials demonstrating that inhibitors of the renin-angiotensin and sympathetic nervous systems can reduce the mortality and morbidity risk associated with heart failure, these drugs have remained underutilized in general clinical practice. In particular, many patients with heart failure due to left ventricular systolic dysfunction fail to receive beta blockers, although this class of drugs, as well as other antihypertensive agents such as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, are recommended as part of routine heart failure therapy by national expert consensus guidelines. In-hospital initiation of beta-blocker therapy may improve long-term utilization by physicians and compliance by patients through obviating many of the misperceived dangers associated with beta blockade. The following review of the clinical trial data from the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) trial, the Metoprolol Controlled-Release Randomized Intervention Trial in Heart Failure (MERIT-HF), the Cardiac Insufficiency Bisoprolol Study II (CIBIS-II), the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial, and the Initiation Management Predischarge Process for Assessment of Carvedilol Therapy for Heart Failure (IMPACT-HF) trial on the efficacy, safety, and tolerability of beta blockers indicates that early initiation can be safely achieved and can improve patient outcomes.

Initial arch wires for tooth alignment during orthodontic treatment with fixed appliances.

PubMed

Jian, Fan; Lai, Wenli; Furness, Susan; McIntyre, Grant T; Millett, Declan T; Hickman, Joy; Wang, Yan

2013-04-30

Initial arch wires are the first arch wires to be inserted into the fixed appliance at the beginning of orthodontic treatment and are used mainly for the alignment of teeth by correcting crowding and rotations. With a number of different types of orthodontic arch wires available for initial tooth alignment, it is important to understand which wire is most efficient, as well as which wires cause the least amount of root resorption and pain during the initial aligning stage of treatment. This is an update of the review 'Initial arch wires for alignment of crooked teeth with fixed orthodontic braces' first published in the Cochrane Database of Systematic Reviews 2010, Issue 4. To assess the effects of initial arch wires for alignment of teeth with fixed orthodontic braces in relation to alignment speed, root resorption and pain intensity. We searched the following electronic databases: the Cochrane Oral Health Group's Trials Register (to 2 August 2012), CENTRAL (The Cochrane Library 2012, Issue 7), MEDLINE via OVID (1950 to 2 August 2012) and EMBASE via OVID (1980 to 2 August 2012). We also searched the reference lists of relevant articles. There was no restriction with regard to publication status or language of publication. We contacted all authors of included studies to identify additional studies. We included randomised controlled trials (RCTs) of initial arch wires to align teeth with fixed orthodontic braces. Only studies involving participants with upper and/or lower full arch fixed orthodontic appliances were included. Two review authors were responsible for study selection, validity assessment and data extraction. All disagreements were resolved by discussion amongst the review team. Corresponding authors of included studies were contacted to obtain missing information. Nine RCTs with 571 participants were included in this review. All trials were at high risk of bias and a number of methodological limitations were identified. All trials had at least one potentially confounding factor (such as bracket type, slot size, ligation method, extraction of teeth) which is likely to have influenced the outcome and was not controlled in the trial. None of the trials reported the important adverse outcome of root resorption.Three groups of comparisons were made.(1) Multistrand stainless steel initial arch wires compared to superelastic nickel titanium (NiTi) initial arch wires. There were four trials in this group, with different comparisons and outcomes reported at different times. No meta-analysis was possible. There is insufficient evidence from these trials to determine whether or not there is a difference in either rate of alignment or pain between stainless steel and NiTi initial arch wires.(2) Conventional (stabilised) NiTi initial arch wires compared to superelastic NiTi initial arch wires. There were two trials in this group, one reporting the outcome of alignment over 6 months and the other reporting pain over 1 week. There is insufficient evidence from these trials to determine whether or not there is any difference between conventional (stabilised) and superelastic NiTi initial arch wires with regard to either alignment or pain.(3) Single-strand superelastic NiTi initial arch wires compared to other NiTi (coaxial, copper NiTi (CuNiTi) or thermoelastic) initial arch wires. The three trials in this comparison each compared a different product against single-strand superelastic NiTi. There is very weak unreliable evidence, based on one very small study (n = 24) at high risk of bias, that coaxial superelastic NiTi may produce greater tooth movement over 12 weeks, but no information on associated pain or root resorption. This result should be interpreted with caution until further research evidence is available. There is insufficient evidence to determine whether or not there is a difference between either thermoelastic or CuNiTi and superelastic NiTi initial arch wires. There is no reliable evidence from the trials included in this review that any specific initial arch wire material is better or worse than another with regard to speed of alignment or pain. There is no evidence at all about the effect of initial arch wire materials on the important adverse effect of root resorption. Further well-designed and conducted, adequately-powered, RCTs are required to determine whether the performance of initial arch wire materials as demonstrated in the laboratory, makes a clinically important difference to the alignment of teeth in the initial stage of orthodontic treatment in patients.

Portfolio of prospective clinical trials including brachytherapy: an analysis of the ClinicalTrials.gov database.

PubMed

Cihoric, Nikola; Tsikkinis, Alexandros; Miguelez, Cristina Gutierrez; Strnad, Vratislav; Soldatovic, Ivan; Ghadjar, Pirus; Jeremic, Branislav; Dal Pra, Alan; Aebersold, Daniel M; Lössl, Kristina

2016-03-22

To evaluate the current status of prospective interventional clinical trials that includes brachytherapy (BT) procedures. The records of 175,538 (100 %) clinical trials registered at ClinicalTrials.gov were downloaded on September 2014 and a database was established. Trials using BT as an intervention were identified for further analyses. The selected trials were manually categorized according to indication(s), BT source, applied dose rate, primary sponsor type, location, protocol initiator and funding source. We analyzed trials across 8 available trial protocol elements registered within the database. In total 245 clinical trials were identified, 147 with BT as primary investigated treatment modality and 98 that included BT as an optional treatment component or as part of the standard treatment. Academic centers were the most frequent protocol initiators in trials where BT was the primary investigational treatment modality (p < 0.01). High dose rate (HDR) BT was the most frequently investigated type of BT dose rate (46.3 %) followed by low dose rate (LDR) (42.0 %). Prostate was the most frequently investigated tumor entity in trials with BT as the primary treatment modality (40.1 %) followed by breast cancer (17.0 %). BT was rarely the primary investigated treatment modality for cervical cancer (6.8 %). Most clinical trials using BT are predominantly in early phases, investigator-initiated and with low accrual numbers. Current investigational activities that include BT mainly focus on prostate and breast cancers. Important questions concerning the optimal usage of BT will not be answered in the near future.

In-App Reflection Guidance: Lessons Learned Across Four Field Trials at the Workplace

ERIC Educational Resources Information Center

Fessl, Angela; Wesiak, Gudrun; Rivera-Pelayo, Verónica; Feyertag, Sandra; Pammer, Viktoria

2017-01-01

This paper presents a concept for in-app reflection guidance and its evaluation in four work-related field trials. By synthesizing across four field trials, we can show that computer-based reflection guidance can function in the workplace, in the sense of being accepted as technology, being perceived as useful and leading to reflective learning.…

InterGeo II: International Geographical Achievement Test. Field Trials Report and Test (Secondary Schools, Grade 8).

ERIC Educational Resources Information Center

Niemz, Gunter; Stoltman, Joseph P.

InterGeo II, a project of the Commission on Geographical Education (CGE) of the International Geographical Union (IGU), has developed a broadly based, field-trialed testing instrument for making cross-national comparisons of achievement in geography. Field trials of InterGeo II were held in 23 countries. Data were analyzed for national achievement…

Rapid Antiretroviral Therapy Initiation for Women in an HIV-1 Prevention Clinical Trial Experiencing Primary HIV-1 Infection during Pregnancy or Breastfeeding.

PubMed

Morrison, Susan; John-Stewart, Grace; Egessa, John J; Mubezi, Sezi; Kusemererwa, Sylvia; Bii, Dennis K; Bulya, Nulu; Mugume, Francis; Campbell, James D; Wangisi, Jonathan; Bukusi, Elizabeth A; Celum, Connie; Baeten, Jared M

2015-01-01

During an HIV-1 prevention clinical trial in East Africa, we observed 16 cases of primary HIV-1 infection in women coincident with pregnancy or breastfeeding. Nine of eleven pregnant women initiated rapid combination antiretroviral therapy (ART), despite having CD4 counts exceeding national criteria for ART initiation; breastfeeding women initiated ART or replacement feeding. Rapid ART initiation during primary HIV-1 infection during pregnancy and breastfeeding is feasible in this setting.

Criteria for Identifying and Evaluating Candidate Sites for Open-Field Trials of Genetically Engineered Mosquitoes

PubMed Central

Brown, David M.; Alphey, Luke S.; McKemey, Andrew; Beech, Camilla

2014-01-01

Abstract Recent laboratory successes in the development of genetically engineered mosquitoes for controlling pathogen transmission have fostered the need for standardized procedures for advancing the technical achievements to practical tools. It is incumbent in many cases for the same scientists doing the in-laboratory discovery research to also take on the initial challenges of developing the pathway that will move the technologies to the field. One of these challenges is having a set of criteria for selecting collaborators and sites for efficacy and safety field trials that combine rigorous science with good ethical and legal practices. Specific site-selection criteria were developed in four categories—Scientific, Regulatory, Community Engagement, and Resources—in anticipation of open-field releases of a transgenic mosquito strain designed to suppress populations of the dengue vector mosquito, Aedes aegypti. The criteria are derived from previous published material, discussions, and personal experiences with the expectation of providing guidance to laboratory scientists for addressing the conceptual and operational considerations for identifying partner researchers and countries with whom to collaborate. These criteria are not intended to be prescriptive nor can they be applied to every circumstance where genetic approaches are proposed for deployment. However, we encourage those involved in the discovery phase of research to consider each criterion during project planning activities, and where appropriate, incorporate them into a “go/no-go” decision-making process for further development and testing of the technologies. PMID:24689963

[Dialectical Behavior Therapy (DBT)--developments and empirical evidence].

PubMed

Burmeister, Kerstin; Höschel, Klaus; von Auer, Anne Kristin; Reiske, Sophie; Schweiger, Ulrich; Sipos, Valerija; Philipsen, Alexandra; Priebe, Kathlen; Bohus, Martin

2014-07-01

Dialectical Behavior Therapy has been initially designed and evaluated as an outpatient-treatment program for chronic suicidal female patients. Within the last years, several adaptations of DBT for specific comorbidities, other settings or other disorders related to emotion dysregulation have been developed. This report reviews conceptual aspects and the scientific evidence of initially designed Dialectical Behavior Therapy and the adaptations. Systematic literature search and systematic review. Recently, two meta-analyses which are based on randomized controlled trials conclude robust and stabile effects of DBT Evidence from further RCTs and other studies show promise for the properties of many DBT adaptations. The current review of the literature suggests a good effectiveness of DBT, especially on complex disorders with deficits in the field of emotion regulation. © Georg Thieme Verlag KG Stuttgart · New York.

Between-Subject Variability in the Breaking Continuous Flash Suppression Paradigm: Potential Causes, Consequences, and Solutions

PubMed Central

Gayet, Surya; Stein, Timo

2017-01-01

A recent focus in the field of consciousness research involves investigating the propensity of initially non-conscious visual information to gain access to consciousness. A critical tool for measuring conscious access is the so-called breaking continuous flash suppression paradigm (b-CFS). In this paradigm, a high contrast dynamic pattern is presented to one eye, thereby temporarily suppressing a target stimulus that is presented to the other eye. The time it takes for observers to report (e.g., the location of) the initially suppressed stimulus provides a measure of conscious access. Typical observations in b-CFS studies include the finding that upright faces are released from suppression faster than inverted faces, and the finding that stimuli that match the current content of visual working memory are released from suppression faster than mismatching stimuli. Interestingly, the extent to which observers exhibit these effects varies extensively (in the range of hundreds of milliseconds). By re-analyzing existing datasets and a new dataset we establish that the difference in RTs between conditions in b-CFS tasks (i.e., the effect of interest) is highly correlated with participants' overall suppression durations, and with their trial-to-trial variability in RTs. We advocate the usage of a simple latency- normalization method, which (1) removes the between-subject variability in suppression duration from the effect of interest, while (2) providing distributions of RT differences that are better suited for parametric testing. We next compare this latency-normalization method to two other transformations that are widely applied on within-subject RT data (z-transformations and log-transformations). Finally, we tentatively discuss how trial-to-trial variability and overall suppression duration might relate to prolonged phases of shallow suppression that are more prone to modulations of conscious access. PMID:28396645

A systematic review of randomised controlled trials evaluating the effect of mother/baby skin-to-skin care on successful breast feeding.

PubMed

Carfoot, Sue; Williamson, Paula R; Dickson, Rumona

2003-06-01

to examine the effects of early skin-to-skin contact between mother and baby on the initiation and duration of breast feeding. electronic databases--the Cochrane Library, MEDLINE,CINAHL and EMBASE. References of studies were examined to identify additional trials and contact was made with researchers in the field. Study selection criteria: randomised or quasi-randomised controlled trials in any language in which skin-to-skin contact between mothers and their healthy full-term newborn babies was compared to routine contact. Primary outcomes were success of first breast feed and duration of breast feeding. Secondary outcomes included, baby temperature and behaviour. STUDY-QUALITY ASSESSMENT: validity of included studies was assessed using criteria defined by the Cochrane Collaboration. Application of inclusion criteria, validity assessment and data extraction were carried out independently by two reviewers with a third reviewer to resolve differences. seven randomised controlled trials were identified. Five studies assessed duration of breast feeding with mixed results. None of the studies assessed the success of the first breast-feeding experience. Study quality was variable with methods of randomisation and blinding of assessment unclear in four of the five studies providing relevant results. the findings of this systematic review fail to support the current initiatives to implement changes in clinical practice to include skin-to-skin contact. Methodological flaws within the included studies prohibit firm conclusions being reached with regard to the effect of skin-to-skin contact on the duration of breast feeding, timing of first breast feed or baby physiological factors. The review highlights the need for further primary research to assess the effect of skin-to-skin contact on the breast-feeding experience.

Performance evaluation of ALCAN-AASF50-ferric coated activated alumina and granular ferric hydroxide (GFH) for arsenic removal in the presence of competitive ions in an active well :Kirtland field trial - initial studies.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neidel, Linnah L.; Krumhansl, James Lee; Siegel, Malcolm Dean

This report documents a field trial program carried out at Well No.15 located at Kirtland Air Force Base, Albuquerque, New Mexico, to evaluate the performance of two relatively new arsenic removal media, ALCAN-AASF50 (ferric coated activated alumina) and granular ferric hydroxide (US Filter-GFH). The field trial program showed that both media were able to remove arsenate and meet the new total arsenic maximum contaminant level (MCL) in drinking water of 10 {micro}g/L. The arsenate removal capacity was defined at a breakthrough effluent concentration of 5 {micro}g/L arsenic (50% of the arsenic MCL of 10 {micro}g/L). At an influent pH ofmore » 8.1 {+-} 0.4, the arsenate removal capacity of AASF50 was 33.5 mg As(V)/L of dry media (29.9 {micro}g As(V)/g of media on a dry basis). At an influent pH of 7.2 {+-} 0.3, the arsenate removal capacity of GFH was 155 mg As(V)/L of wet media (286 {micro}g As(V)/g of media on a dry basis). Silicate, fluoride, and bicarbonate ions are removed by ALCAN AASF50. Chloride, nitrate, and sulfate ions were not removed by AASF50. The GFH media also removed silicate and bicarbonate ions; however, it did not remove fluoride, chloride, nitrate, and sulfate ions. Differences in the media performance partly reflect the variations in the feed-water pH between the 2 tests. Both the exhausted AASF50 and GFH media passed the Toxicity Characteristic Leaching Procedure (TCLP) test with respect to arsenic and therefore could be disposed as nonhazardous waste.« less

International models of investigator-initiated trials: implications for Japan

PubMed Central

Trimble, E. L.; Ledermann, J.; Law, K.; Miyata, T.; Imamura, C. K.; Nam, B.-H.; Kim, Y.H.; Bang, Y.-J.; Michaels, M.; Ardron, D.; Amano, S.; Ando, Y.; Tominaga, T.; Kurokawa, K.; Takebe, N.

2012-01-01

Background Academic/institutional investigator-initiated clinical trials benefit individuals and society by supplementing gaps in industry-sponsored clinical trials. Materials In May 2010, experts from Japan, the Republic of Korea, the UK, and the United States, met at a symposium in Tokyo, Japan, to discuss how policies related to the conduct of clinical trials, which have been shown to be effective, may be applied to other regions of the world. Results In order to increase the availability of anticancer drugs world-wide, nations including Japan should examine the benefits of increasing the number of investigator-initiated clinical trials. These trials represent one of the most effective ways to translate basic scientific knowledge into clinical practice. These trials should be conducted under GCP guidelines and include Investigational New Drug application submissions with the ultimate goal of future drug approval. Conclusions To maximize the effectiveness of these trials, a policy to educate health care professionals, cancer patients and their families, and the public in general on the benefits of clinical trials should be strengthened. Finally, policies that expedite the clinical development of novel cancer drugs which have already been shown to be effective in other countries are needed in many nations including Japan to accelerate drug approval. PMID:22843420

Syringe Pump Performance Maintained with IV Filter Use During Low Flow Rate Delivery for Pediatric Patients.

PubMed

Chau, Destiny F; Vasilopoulos, Terrie; Schoepf, Miriam; Zhang, Christina; Fahy, Brenda G

2016-09-01

Complex surgical and critically ill pediatric patients rely on syringe infusion pumps for precise delivery of IV medications. Low flow rates and in-line IV filter use may affect drug delivery. To determine the effects of an in-line filter to remove air and/or contaminants on syringe pump performance at low flow rates, we compared the measured rates with the programmed flow rates with and without in-line IV filters. Standardized IV infusion assemblies with and without IV filters (filter and control groups) attached to a 10-mL syringe were primed and then loaded onto a syringe pump and connected to a 16-gauge, 16-cm single-lumen catheter. The catheter was suspended in a normal saline fluid column to simulate the back pressure from central venous circulation. The delivered infusate was measured by gravimetric methods at predetermined time intervals, and flow rate was calculated. Experimental trials for initial programmed rates of 1.0, 0.8, 0.6, and 0.4 mL/h were performed in control and filter groups. For each trial, the flow rate was changed to double the initial flow rate and was then returned to the initial flow rate to analyze pump performance for titration of rates often required during medication administration. These conditions (initial rate, doubling of initial rate, and return to initial rate) were analyzed separately for steady-state flow rate and time to steady state, whereas their average was used for percent deviation analysis. Differences between control and filter groups were assessed using Student t tests with adjustment for multiplicity (using n = 3 replications per group). Mean time from 0 to initial flow (startup delay) was <1 minute in both groups with no statistical difference between groups (P = 1.0). The average time to reach steady-state flow after infusion startup or rate changes was not statistically different between the groups (range, 0.8-5.5 minutes), for any flow rate or part of the trial (initial rate, doubling of initial rate, and return to initial rate), although the study was underpowered to detect small time differences. Overall, the mean steady-state flow rate for each trial was below the programmed flow rate with negative mean percent deviations for each trial. In the 1.0-mL/h initial rate trial, the steady-state flow rate attained was lower in the filter than the control group for the initial rate (P = 0.04) and doubling of initial rate (P = 0.04) with a trend during the return to initial rate (P = 0.06), although this same effect was not observed when doubling the initial rate trials of 0.8 or 0.6 mL/h or any other rate trials compared with the control group. With low flow rates used in complex surgical and pediatric critically ill patients, the addition of IV filters did not confer statistically significant changes in startup delay, flow variability, or time to reach steady-state flow of medications administered by syringe infusion pumps. The overall flow rate was lower than programmed flow rate with or without a filter.

The EU-project United4Health: User-centred design of an information system for a Norwegian telemedicine service.

PubMed

Smaradottir, Berglind; Gerdes, Martin; Martinez, Santiago; Fensli, Rune

2016-10-01

Organizational changes of health care services in Norway brought to light a need for new clinical pathways. This study presents the design and evaluation of an information system for a new telemedicine service for chronic obstructive pulmonary disease patients after hospital discharge. A user-centred design approach was employed composed of a workshop with end-users, two user tests and a field trial. For data collection, qualitative methods such as observations, semi-structured interviews and a questionnaire were used. User workshop's outcome informed the implementation of the system initial prototype, evaluated by end-users in a usability laboratory. Several usability and functionality issues were identified and solved, such as the interface between the initial colour scheme and the triage colours. Iterative refinements were made and a second user evaluation showed that the main issues were solved. The responses to a questionnaire presented a high score of user satisfaction. In the final phase, a field trial showed satisfactory use of the system. This study showed how the target end-users groups were actively involved in identifying the needs, suggestions and preferences. These aspects were addressed in the development of an information system through a user-centred design process. The process efficiently enabled users to give feedback about design and functionality. Continuous refinement of the system was the key to full development and suitability for the telemedicine service. This research was a result of the international cooperation between partners within the project United4Health, a part of the Seventh Framework Programme for Research of the European Union. © The Author(s) 2015.

Preparing beginning reading teachers: An experimental comparison of initial early literacy field experiences.

PubMed

Al Otaiba, Stephanie; Lake, Vickie E; Greulich, Luana; Folsom, Jessica S; Guidry, Lisa

2012-01-01

This randomized-control trial examined the learning of preservice teachers taking an initial Early Literacy course in an early childhood education program and of the kindergarten or first grade students they tutored in their field experience. Preservice teachers were randomly assigned to one of two tutoring programs: Book Buddies and Tutor Assisted Intensive Learning Strategies (TAILS), which provided identical meaning-focused instruction (shared book reading), but differed in the presentation of code-focused skills. TAILS used explicit, scripted lessons, and the Book Buddies required that code-focused instruction take place during shared book reading. Our research goal was to understand which tutoring program would be most effective in improving knowledge about reading, lead to broad and deep language and preparedness of the novice preservice teachers, and yield the most successful student reading outcomes. Findings indicate that all pre-service teachers demonstrated similar gains in knowledge, but preservice teachers in the TAILS program demonstrated broader and deeper application of knowledge and higher self-ratings of preparedness to teach reading. Students in both conditions made similar comprehension gains, but students tutored with TAILS showed significantly stronger decoding gains.

On the breakdown modes and parameter space of Ohmic Tokamak startup

NASA Astrophysics Data System (ADS)

Peng, Yanli; Jiang, Wei; Zhang, Ya; Hu, Xiwei; Zhuang, Ge; Innocenti, Maria; Lapenta, Giovanni

2017-10-01

Tokamak plasma has to be hot. The process of turning the initial dilute neutral hydrogen gas at room temperature into fully ionized plasma is called tokamak startup. Even with over 40 years of research, the parameter ranges for the successful startup still aren't determined by numerical simulations but by trial and errors. However, in recent years it has drawn much attention due to one of the challenges faced by ITER: the maximum electric field for startup can't exceed 0.3 V/m, which makes the parameter range for successful startup narrower. Besides, this physical mechanism is far from being understood either theoretically or numerically. In this work, we have simulated the plasma breakdown phase driven by pure Ohmic heating using a particle-in-cell/Monte Carlo code, with the aim of giving a predictive parameter range for most tokamaks, even for ITER. We have found three situations during the discharge, as a function of the initial parameters: no breakdown, breakdown and runaway. Moreover, breakdown delay and volt-second consumption under different initial conditions are evaluated. In addition, we have simulated breakdown on ITER and confirmed that when the electric field is 0.3 V/m, the optimal pre-filling pressure is 0.001 Pa, which is in good agreement with ITER's design.

The Robustness of Designs for Trials with Nested Data against Incorrect Initial Intracluster Correlation Coefficient Estimates

ERIC Educational Resources Information Center

Korendijk, Elly J. H.; Moerbeek, Mirjam; Maas, Cora J. M.

2010-01-01

In the case of trials with nested data, the optimal allocation of units depends on the budget, the costs, and the intracluster correlation coefficient. In general, the intracluster correlation coefficient is unknown in advance and an initial guess has to be made based on published values or subject matter knowledge. This initial estimate is likely…

Partnerships and pathways of dissemination: the National Institute on Drug Abuse-Substance Abuse and Mental Health Services Administration Blending Initiative in the Clinical Trials Network.

PubMed

Martino, Steve; Brigham, Gregory S; Higgins, Christine; Gallon, Steve; Freese, Thomas E; Albright, Lonnetta M; Hulsey, Eric G; Krom, Laurie; Storti, Susan A; Perl, Harold; Nugent, Cathrine D; Pintello, Denise; Condon, Timothy P

2010-06-01

Since 2001, the National Drug Abuse Treatment Clinical Trials Network (CTN) has worked to put the results of its trials into the hands of community treatment programs, in large part through its participation in the National Institute on Drug Abuse-Substance Abuse and Mental Health Services Administration Blending Initiative and its close involvement with the Center for Substance Abuse Treatment's Addiction Technology Transfer Centers. This article describes (a) the CTN's integral role in the Blending Initiative, (b) key partnerships and dissemination pathways through which the results of CTN trials are developed into blending products and then transferred to community treatment programs, and (c) three blending initiatives involving buprenorphine, motivational incentives, and motivational interviewing. The Blending Initiative has resulted in high utilization of its products, preparation of more than 200 regional trainers, widespread training of service providers in most U.S. States, Puerto Rico, and the U.S. Virgin Islands and movement toward the development of Web-based implementation supports and technical assistance. Implications for future directions of the Blending Initiative and opportunities for research are discussed.

The influence of an uncertain force environment on reshaping trial-to-trial motor variability.

PubMed

Izawa, Jun; Yoshioka, Toshinori; Osu, Rieko

2014-09-10

Motor memory is updated to generate ideal movements in a novel environment. When the environment changes every trial randomly, how does the brain incorporate this uncertainty into motor memory? To investigate how the brain adapts to an uncertain environment, we considered a reach adaptation protocol where individuals practiced moving in a force field where a noise was injected. After they had adapted, we measured the trial-to-trial variability in the temporal profiles of the produced hand force. We found that the motor variability was significantly magnified by the adaptation to the random force field. Temporal profiles of the motor variance were significantly dissociable between two different types of random force fields experienced. A model-based analysis suggests that the variability is generated by noise in the gains of the internal model. It further suggests that the trial-to-trial motor variability magnified by the adaptation in a random force field is generated by the uncertainty of the internal model formed in the brain as a result of the adaptation.

Clinical trials recruitment planning: A proposed framework from the Clinical Trials Transformation Initiative.

PubMed

Huang, Grant D; Bull, Jonca; Johnston McKee, Kelly; Mahon, Elizabeth; Harper, Beth; Roberts, Jamie N

2018-03-01

Patient recruitment is widely recognized as a key determinant of success for clinical trials. Yet a substantial number of trials fail to reach recruitment goals-a situation that has important scientific, financial, ethical, and policy implications. Further, there are important effects on stakeholders who directly contribute to the trial including investigators, sponsors, and study participants. Despite efforts over multiple decades to identify and address barriers, recruitment challenges persist. To advance a more comprehensive approach to trial recruitment, the Clinical Trials Transformation Initiative (CTTI) convened a project team to examine the challenges and to issue actionable, evidence-based recommendations for improving recruitment planning that extend beyond common study-specific strategies. We describe our multi-stakeholder effort to develop a framework that delineates three areas essential to strategic recruitment planning efforts: (1) trial design and protocol development, (2) trial feasibility and site selection, and (3) communication. Our recommendations propose an upstream approach to recruitment planning that has the potential to produce greater impact and reduce downstream barriers. Additionally, we offer tools to help facilitate adoption of the recommendations. We hope that our framework and recommendations will serve as a guide for initial efforts in clinical trial recruitment planning irrespective of disease or intervention focus, provide a common basis for discussions in this area and generate targets for further analysis and continual improvement. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of a pulsed electromagnetic therapy on multiple sclerosis fatigue and quality of life: a double-blind, placebo controlled trial.

PubMed

Lappin, Martha S; Lawrie, Fraser Wilson; Richards, Todd L; Kramer, Eric D

2003-01-01

There is a growing literature on the biological and clinical effects of pulsed electromagnetic fields. Some studies suggest that electromagnetic therapies may be useful in the treatment of chronic illnesses. This study is a follow-up to a placebo controlled pilot study in which multiple sclerosis (MS) patients exposed to weak, extremely low frequency pulsed electromagnetic fields showed significant improvements on a composite symptom measure. To evaluate the effects of a pulsed electromagnetic therapy on MS related fatigue, spasticity, bladder control, and overall quality of life. A multi-site, double-blind, placebo controlled, crossover trial. Each subject received 4 weeks of the active and placebo treatments separated by a 2-week washout period. The University of Washington Medical Center in Seattle Wash, the Neurology Center of Fairfax in Fairfax, Va, and the headquarters of the Multiple Sclerosis Association of America in Cherry Hill, NJ. 117 patients with clinically definite MS. Daily exposure to a small, portable pulsing electromagnetic field generator. The MS Quality of Life Inventory (MSQLI) was used to assess changes in fatigue, bladder control, spasticity, and a quality of life composite. Paired t-tests were used to assess treatment differences in the 117 subjects (81% of the initial sample) who completed both treatment sessions. Improvements in fatigue and overall quality of life were significantly greater on the active device. There were no treatment effects for bladder control and a disability composite, and mixed results for spasticity. Evidence from this randomized, double-bind, placebo controlled trial is consistent with results from smaller studies suggesting that exposure to pulsing, weak electromagnetic fields can alleviate symptoms of MS. The clinical effects were small, however, and need to be replicated. Additional research is also needed to examine the possibility that ambulatory patients and patients taking interferons for their MS may be most responsive to this kind of treatment.

Bone regeneration: stem cell therapies and clinical studies in orthopaedics and traumatology.

PubMed

Gómez-Barrena, Enrique; Rosset, Philippe; Müller, Ingo; Giordano, Rosaria; Bunu, Carmen; Layrolle, Pierre; Konttinen, Yrjö T; Luyten, Frank P

2011-06-01

Regenerative medicine seeks to repair or replace damaged tissues or organs, with the goal to fully restore structure and function without the formation of scar tissue. Cell based therapies are promising new therapeutic approaches in regenerative medicine. By using mesenchymal stem cells, good results have been reported for bone engineering in a number of clinical studies, most of them investigator initiated trials with limited scope with respect to controls and outcome. With the implementation of a new regulatory framework for advanced therapeutic medicinal products, the stage is set to improve both the characterization of the cells and combination products, and pave the way for improved controlled and well-designed clinical trials. The incorporation of more personalized medicine approaches, including the use of biomarkers to identify the proper patients and the responders to treatment, will be contributing to progress in the field. Both translational and clinical research will move the boundaries in the field of regenerative medicine, and a coordinated effort will provide the clinical breakthroughs, particularly in the many applications of bone engineering. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Recruitment and Retention for a Weight Loss Maintenance Trial Involving Weight Loss Prior to Randomization

PubMed Central

Grubber, J. M.; McVay, M. A.; Olsen, M. K.; Bolton, J.; Gierisch, J. M.; Taylor, S. S.; Maciejewski, M. L.; Yancy, W. S.

2016-01-01

Abstract Objective A weight loss maintenance trial involving weight loss prior to randomization is challenging to implement due to the potential for dropout and insufficient weight loss. We examined rates and correlates of non‐initiation, dropout, and insufficient weight loss during a weight loss maintenance trial. Methods The MAINTAIN trial involved a 16‐week weight loss program followed by randomization among participants losing at least 4 kg. Psychosocial measures were administered during a screening visit. Weight was obtained at the first group session and 16 weeks later to determine eligibility for randomization. Results Of 573 patients who screened as eligible, 69 failed to initiate the weight loss program. In adjusted analyses, failure to initiate was associated with lower age, lack of a support person, and less encouragement for making dietary changes. Among participants who initiated, 200 dropped out, 82 lost insufficient weight, and 222 lost sufficient weight for randomization. Compared to losing sufficient weight, dropping out was associated with younger age and tobacco use, whereas losing insufficient weight was associated with non‐White race and controlled motivation for physical activity. Conclusions Studies should be conducted to evaluate strategies to maximize recruitment and retention of subgroups that are less likely to initiate and be retained in weight loss maintenance trials. PMID:28090340

WITHDRAWN: Initial management strategies for dyspepsia.

PubMed

Delaney, Brendan; Ford, Alex C; Forman, David; Moayyedi, Paul; Qume, Michelle

2009-10-07

This review considers management strategies (combinations of initial investigation and empirical treatments) for dyspeptic patients. Dyspepsia was defined to include both epigastric pain and heartburn. To determine the effectiveness, acceptability, and cost effectiveness of the following initial management strategies for patients presenting with dyspepsia (a) Initial pharmacological therapy (including endoscopy for treatment failures). (b) Early endoscopy. (c) Testing for Helicobacter pylori (H. pylori )and endoscope only those positive. (d) H. pylori eradication therapy with or without prior testing. Trials were located through electronic searches and extensive contact with trialists. All randomised controlled trials of dyspeptic patients presenting in primary care. Data were collected on dyspeptic symptoms, quality of life and use of resources. An individual patient data meta-analysis of health economic data was conducted Twenty-five papers reporting 27 comparisons were found. Trials comparing proton pump inhibitors (PPI) with antacids (three trials) and histamine H2-receptor antagonists (H2RAs) (three trials), early endoscopy with initial acid suppression (five trials), H. pylori test and endoscope versus usual management (three trials), H. pylori test and treat versus endoscopy (six trials), and test and treat versus acid suppression alone in H. pylori positive patients (four trials), were pooled. PPIs were significantly more effective than both H2RAs and antacids. Relative risks (RR) and 95% confidence intervals (CI) were; for PPI compared with antacid 0.72 (95% CI 0.64 to 0.80), PPI compared with H2RA 0.63 (95% CI 0.47 to 0.85). Results for other drug comparisons were either absent or inconclusive. Initial endoscopy was associated with a small reduction in the risk of recurrent dyspeptic symptoms compared with H. pylori test and treat (OR 0.75, 95% CI 0.58 to 0.96), but was not cost effective (mean additional cost of endoscopy US$401 (95% CI $328 to 474). Test and treat may be more effective than acid suppression alone (RR 0.59 95% CI 0.42 to 0.83). Proton pump inhibitor drugs (PPIs) are effective in the treatment of dyspepsia in these trials which may not adequately exclude patients with gastro-oesophageal reflux disease (GORD). The relative efficacy of histamine H2-receptor antagonists (H2RAs) and PPIs is uncertain. Early investigation by endoscopy or H. pylori testing may benefit some patients with dyspepsia but is not cost effective as part of an overall management strategy.

Wash and Wean: Bathing Patients Undergoing Weaning Trials During Prolonged Mechanical Ventilation

PubMed Central

Happ, Mary Beth; Tate, Judith A.; Swigart, Valerie A.; DiVirgilio-Thomas, Dana; Hoffman, Leslie A.

2010-01-01

BACKGROUND Bathing is a fundamental nursing care activity performed for or with the self-assistance of critically ill patients. Few studies address caregiver and/or patient-family perspectives about bathing activity during weaning from prolonged mechanical ventilation. OBJECTIVE To describe practices and beliefs about bathing patients during weaning from prolonged mechanical ventilation (PMV). METHODS Secondary analysis of qualitative data (observational field notes, interviews, and clinical record review) from a larger ethnographic study involving 30 patients weaning from PMV and the clinicians who cared for them using basic qualitative description. RESULTS Bathing, hygiene, and personal care were highly valued and equated with “good” nursing care by families and nurses. Nurses and respiratory therapists reported “working around” bath time and promoted conducting weaning trials before or after bathing. Patients were nevertheless bathed during weaning trials despite clinicians expressed concerns for energy conservation. Clinicians’ recognized individual patient response to bathing during PMV weaning trials. CONCLUSION Bathing is a central care activity for PMV patients and a component of daily work processes in the ICU. Bathing requires assessment of patient condition and activity tolerance and nurse-respiratory therapist negotiation and accommodation with respect to the initiation and/or continuation of PMV weaning trials during bathing. Further study is needed to validate the impact (or lack of impact) of various timing strategies for bathing PMV patients. PMID:20561877

The STAMPEDE trial: paradigm-changing data through innovative trial design.

PubMed

Carthon, Bradley C; Antonarakis, Emmanuel S

2016-09-01

Despite the numerous regulatory approvals for prostate cancer, metastatic prostate cancer remains a huge burden for men worldwide. In an exciting development, James et al . recently published data from the Systemic Therapy in Advanced or Metastatic Prostate Cancer: Evaluation of Drug Efficacy: a multi-stage multi-arm randomised control trial (STAMPEDE). This is an innovative multi-arm multi-stage (MAMS) trial that has utilized one control arm and several comparator arms in order to provide evidence for the inclusion of therapies beyond standard androgen deprivation alone. The patient population included: (I) men with high-risk, non-metastatic, node-negative disease; (II) men with distant-metastatic or node-positive disease; and (III) men with previously-treated prostate cancer by prostatectomy or definitive radiotherapy presenting with relapse. Men were to continue androgen deprivation for at least 2 years. The current data published by this group supports earlier results and provides additional evidence that docetaxel utilized in an up-front fashion provides a survival benefit in men with hormone-sensitive metastatic prostate cancer. Moreover, the initial results from STAMPEDE show how therapies without a demonstrated survival benefit can be efficiently excluded from further study once the likelihood of a benefit is ruled out by a predetermined analysis. In this piece, we will review the STAMPEDE data, contrast it with existing results, and provide our perspectives on how this will affect future trial conduct in the field of prostate cancer.

Conditionally replicative adenovirus for gastrointestinal cancers.

PubMed

Yamamoto, Masato

2004-08-01

The clinical outcome of advanced gastrointestinal (GI) cancers (especially pancreatic and oesophageal cancers) is dismal, despite the advance of conventional therapeutic strategies. Cancer gene therapy is a category of new therapeutics, among which conditionally replicative adenovirus (CRAd) is one promising strategy to overcome existing obstacles of cancer gene therapy. Various CRAds have been developed for GI cancer treatment by taking advantage of the replication biology of adenovirus. Some CRAds have already been tested in clinical trials, but have fallen short of initial expectations. Concerns for clinical applicability include therapeutic potency, replication selectivity and interval end points in clinical trials. In addition, improvement of experimental animal models is needed for a deeper understanding of CRAd biology. Despite these obstacles, CRAds continue to be an exciting area of investigation with great potential for clinical utility. Further virological and oncological research will eventually lead to full realisation of the therapeutic potential of CRAds in the field of GI cancers.

Regional or general anesthesia for fast-track hip and knee replacement - what is the evidence?

PubMed Central

Kehlet, Henrik; Aasvang, Eske Kvanner

2015-01-01

Regional anesthesia for knee and hip arthroplasty may have favorable outcome effects compared with general anesthesia by effectively blocking afferent input, providing initial postoperative analgesia, reducing endocrine metabolic responses, and providing sympathetic blockade with reduced bleeding and less risk of thromboembolic complications but with undesirable effects on lower limb motor and urinary bladder function. Old randomized studies supported the use of regional anesthesia with fewer postoperative pulmonary and thromboembolic complications, and this has been supported by recent large non-randomized epidemiological database cohort studies. In contrast, the data from newer randomized trials are conflicting, and recent studies using modern general anesthetic techniques may potentially support the use of general versus spinal anesthesia. In summary, the lack of properly designed large randomized controlled trials comparing modern general anesthesia and spinal anesthesia for knee and hip arthroplasty prevents final recommendations and calls for prospective detailed studies in this clinically important field. PMID:26918127

Going viral: a review of replication-selective oncolytic adenoviruses

PubMed Central

Larson, Christopher; Oronsky, Bryan; Scicinski, Jan; Fanger, Gary R.; Stirn, Meaghan; Oronsky, Arnold; Reid, Tony R.

2015-01-01

Oncolytic viruses have had a tumultuous course, from the initial anecdotal reports of patients having antineoplastic effects after natural viral infections a century ago to the development of current cutting-edge therapies in clinical trials. Adenoviruses have long been the workhorse of virotherapy, and we review both the scientific and the not-so-scientific forces that have shaped the development of these therapeutics from wild-type viral pathogens, turning an old foe into a new friend. After a brief review of the mechanics of viral replication and how it has been modified to engineer tumor selectivity, we give particular attention to ONYX-015, the forerunner of virotherapy with extensive clinical testing that pioneered the field. The findings from those as well as other oncolytic trials have shaped how we now view these viruses, which our immune system has evolved to vigorously attack, as promising immunotherapy agents. PMID:26280277

Strategies for sustainable woodland on contaminated soils.

PubMed

Dickinson, N M

2000-07-01

Extensive in situ reclamation treatment technologies are appropriate for a large proportion of contaminated land in place of total removal or complete containment of soil. In this paper, initial results are presented of site descriptions, tree survival and metal uptake patterns from two field planting trials on a highly industrially contaminated site adjacent to a metal refinery and on old sanitary landfill sites. Survival rate was high in both trials but factors besides heavy metals were particularly significant. Uptake patterns of metals into foliage and woody tissues were variable, with substantial uptake in some species and clones supporting the findings of earlier pot experiments. It is argued that there is sufficient evidence to consider the use of trees in reclamation as part of a realistic, integrated, low-cost, ecologically-sound and sustainable reclamation strategy for contaminated land. This is an opportunity to bring a large number of brownfield sites into productive use, which otherwise would be prohibitively expensive to restore.

[Mitoguazone (methylglyoxal bis(guanylhydrazone))--its status and prospects].

PubMed

Hoffmann, H; Gutsche, W; Amlacher, R; Schulze, W; Werner, W; Lenk, H; Wohlrab, W; Haupt, E

1989-01-01

Because of its severe side effects, initial clinical trials of the antineoplastic compound mitoguazone (Methyl-GAG, M-G) were ceased in the middle of 1960s. One decade later pharmacokinetically guided dose schedules as well as new experimental data on the antiproliferative mechanism of action stimulated new clinical studies. First results indicated that M-G had single-agent activity against various tumors such as acute leukemia and malignant lymphoma connected with acceptable tolerance. M-G seems to be effective especially in combination with other antineoplastic drugs. Its final evaluation may be reserved to further randomized trials. Recently, the psoriasis vulgaris is expected to be an additional field of the application of M-G. In this minireview data on synthesis, preclinical pharmacology, pharmacokinetics, biochemical effects and toxicology of M-G are given. Furthermore, clinical findings on M-G concerning its pharmacokinetic behaviour, antitumor and antipsoriatic activities are described.

Improving precision of forage yield trials: A case study

USDA-ARS?s Scientific Manuscript database

Field-based agronomic and genetic research relies heavily on the data generated from field evaluations. Therefore, it is imperative to optimize the precision of yield estimates in cultivar evaluation trials to make reliable selections. Experimental error in yield trials is sensitive to several facto...

Designing a field trial of an equine grass sickness vaccine: A questionnaire-based feasibility study.

PubMed

Ireland, Joanne L; McGorum, Bruce C; Proudman, Christopher J; Newton, J Richard

2016-07-01

Without an experimental model of equine grass sickness (EGS), a randomised controlled field trial (RCT) represents the only method of evaluating the efficacy of Clostridium botulinum type C vaccination in preventing naturally occurring disease. Clinical trial feasibility is an important aspect of preliminary work undertaken prior to initiating RCTs, estimating parameters that are important for study design. This cross-sectional study aimed to assess the feasibility of conducting a nationwide RCT of a candidate vaccine for EGS based on responses from a sample of British equine veterinary practices (n = 119/284). Seventy-three percent of practices had attended ≥1 EGS case within the preceding 2 years (median four cases), and 51.3% regularly attended recurrently affected premises. Veterinary surgeons had greater confidence diagnosing acute/subacute EGS based solely on history and clinical signs compared to chronic EGS. Ninety-one percent of respondents (n = 103/113) considered the proposed RCT to be important/very important to equine veterinary research. Ninety-one percent of respondents (n = 102/112) indicated preparedness to assist in owner recruitment and 92.9% (n = 104/112) indicated willingness to participate in a RCT. The most frequent reasons for practices declining to participate were low incidence of EGS (n = 4), did not believe clients would wish to participate (n = 3) and amount of paperwork/data collection involved (n = 2). There was considerable support amongst participating veterinary practices for a RCT evaluating the efficacy of Clostridium botulinum vaccination for the prevention of EGS in Britain. Substantial proportions of participating practices would be prepared to participate in the RCT and regularly attended EGS-affected premises that would meet trial inclusion criteria. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Translational Pathway Toward a Clinical Trial Using the Second-Generation AAV Micro-Dystrophin Vector

DTIC Science & Technology

responsible for restoring neuronal nitric oxide synthase (nNOS).Failure to restore nNOS significantly contributes to the initiation and progression...model. Our findings have provided the foundation for the recent initiation of human trials.

Series length used during trend analysis affects sensitivity to changes in progression rate in the ocular hypertension treatment study.

PubMed

Gardiner, Stuart K; Demirel, Shaban; De Moraes, Carlos Gustavo; Liebmann, Jeffrey M; Cioffi, George A; Ritch, Robert; Gordon, Mae O; Kass, Michael A

2013-02-15

Trend analysis techniques to detect glaucomatous progression typically assume a constant rate of change. This study uses data from the Ocular Hypertension Treatment Study to assess whether this assumption decreases sensitivity to changes in progression rate, by including earlier periods of stability. Series of visual fields (mean 24 per eye) completed at 6-month intervals from participants randomized initially to observation were split into subseries before and after the initiation of treatment (the "split-point"). The mean deviation rate of change (MDR) was derived using these entire subseries, and using only the window length (W) tests nearest the split-point, for different window lengths of W tests. A generalized estimating equation model was used to detect changes in MDR occurring at the split-point. Using shortened subseries with W = 7 tests, the MDR slowed by 0.142 dB/y upon initiation of treatment (P < 0.001), and the proportion of eyes showing "rapid deterioration" (MDR <-0.5 dB/y with P < 5%) decreased from 11.8% to 6.5% (P < 0.001). Using the entire sequence, no significant change in MDR was detected (P = 0.796), and there was no change in the proportion of eyes progressing (P = 0.084). Window lengths 6 ≤ W ≤ 9 produced similar benefits. Event analysis revealed a beneficial treatment effect in this dataset. This effect was not detected by linear trend analysis applied to entire series, but was detected when using shorter subseries of length between six and nine fields. Using linear trend analysis on the entire field sequence may not be optimal for detecting and monitoring progression. Nonlinear analyses may be needed for long series of fields. (ClinicalTrials.gov number, NCT00000125.).

Spectroscopic Results from the Life in the Atacama (LITA) Project 2004 Field Season

NASA Technical Reports Server (NTRS)

Piatek, J. L.; Moersch, J. E.; Wyatt, M.; Rampey, M.; Cabrol, N. A.; Wettergreen, D. S.; Whittaker, R.; Grin, E. A.; Diaz, G. Chong

2005-01-01

Introduction: The Life in the Atacama (LITA) project includes rover field tests designed to look for life in the arid environment of the Atacama Desert (Chile). Field instruments were chosen to help remote observers identify potential habitats and the presence of life in these habitats, and included two spectrometers for help in identifying the mineralogy of the field sites. Two field trials were undertaken during the 2004 field season. The remote science team had no prior knowledge of the local geology, and relied entirely on orbital images and rover-acquired data to make interpretations. Each field trial lasted approximately one week: the sites for these trials were in different locations, and are designated "Site B" and "Site C."

Study design for the "effect of METOprolol in CARDioproteCtioN during an acute myocardial InfarCtion" (METOCARD-CNIC): a randomized, controlled parallel-group, observer-blinded clinical trial of early pre-reperfusion metoprolol administration in ST-segment elevation myocardial infarction.

PubMed

Ibanez, Borja; Fuster, Valentin; Macaya, Carlos; Sánchez-Brunete, Vicente; Pizarro, Gonzalo; López-Romero, Pedro; Mateos, Alonso; Jiménez-Borreguero, Jesús; Fernández-Ortiz, Antonio; Sanz, Ginés; Fernández-Friera, Leticia; Corral, Ervigio; Barreiro, Maria-Victoria; Ruiz-Mateos, Borja; Goicolea, Javier; Hernández-Antolín, Rosana; Acebal, Carlos; García-Rubira, Juan Carlos; Albarrán, Agustín; Zamorano, José Luis; Casado, Isabel; Valenciano, Juan; Fernández-Vázquez, Felipe; de la Torre, José María; Pérez de Prado, Armando; Iglesias-Vázquez, José Antonio; Martínez-Tenorio, Pedro; Iñiguez, Andrés

2012-10-01

Infarct size predicts post-infarction mortality. Oral β-blockade within 24 hours of a ST-segment elevation acute myocardial infarction (STEMI) is a class-IA indication, however early intravenous (IV) β-blockers initiation is not encouraged. In recent magnetic resonance imaging (MRI)-based experimental studies, the β(1)-blocker metoprolol has been shown to reduce infarct size only when administered before coronary reperfusion. To date, there is not a single trial comparing the pre- vs. post-reperfusion β-blocker initiation in STEMI. The METOCARD-CNIC trial is testing whether the early initiation of IV metoprolol before primary percutaneous coronary intervention (pPCI) could reduce infarct size and improve outcomes when compared to oral post-pPCI metoprolol initiation. The METOCARD-CNIC trial is a randomized parallel-group single-blind (to outcome evaluators) clinical effectiveness trial conducted in 5 Counties across Spain that will enroll 220 participants. Eligible are 18- to 80-year-old patients with anterior STEMI revascularized by pPCI ≤6 hours from symptom onset. Exclusion criteria are Killip-class ≥III, atrioventricular block or active treatment with β-blockers/bronchodilators. Primary end point is infarct size evaluated by MRI 5 to 7 days post-STEMI. Prespecified major secondary end points are salvage-index, left ventricular ejection fraction recovery (day 5-7 to 6 months), the composite of (death/malignant ventricular arrhythmias/reinfarction/admission due to heart failure), and myocardial perfusion. The METOCARD-CNIC trial is testing the hypothesis that the early initiation of IV metoprolol pre-reperfusion reduces infarct size in comparison to initiation of oral metoprolol post-reperfusion. Given the implications of infarct size reduction in STEMI, if positive, this trial might evidence that a refined use of an approved inexpensive drug can improve outcomes of patients with STEMI. Copyright © 2012 Mosby, Inc. All rights reserved.

Trial Registration at ClinicalTrials.gov between May and October 2005

PubMed Central

Zarin, Deborah A.; Tse, Tony; Ide, Nicholas C.

2006-01-01

BACKGROUND Clinical trial registration allows interested parties to obtain information about ongoing and completed trials, but there are few data indicating the quality of the information provided during the registration process. We used information in the publicly available ClinicalTrials.gov database to describe patterns of trial registration before and after the implementation by journal editors of a new policy requiring registration as a prerequisite for publication. METHODS We reviewed ClinicalTrials.gov records to determine patterns of completion of the “Intervention Name” and “Primary Outcome Measure” data fields for trials registered on May 20 and October 11, 2005, and for trials registered during the interval between these two dates, inclusively. RESULTS During the interval studied, the number of registrations in ClinicalTrials.gov increased by 73 percent from 13,153 to 22,714. The percentage of interventional trials registered by industry with nonspecific Intervention Name entries (attributable to four drug companies) decreased from 10 percent to 2 percent; all other industry and nonindustry records contained specific entries in this field. Of the 2670 studies registered by industry between the two dates, 76 percent provided information in the Primary Outcome Measure field, although these entries varied markedly in their degree of specificity. In the remaining 24 percent of the records, this field was blank. CONCLUSIONS During the summer of 2005, there were large increases in the number of clinical trial registrations. Overall, the data contained in records were more complete in October than they were in May, but there still is room for substantial improvement. PMID:16382064

Parents' perceived obstacles to pediatric clinical trial participation: Findings from the clinical trials transformation initiative.

PubMed

Greenberg, Rachel G; Gamel, Breck; Bloom, Diane; Bradley, John; Jafri, Hasan S; Hinton, Denise; Nambiar, Sumathi; Wheeler, Chris; Tiernan, Rosemary; Smith, P Brian; Roberts, Jamie; Benjamin, Daniel K

2018-03-01

Enrollment of children into pediatric clinical trials remains challenging. More effective strategies to improve recruitment of children into trials are needed. This study used in-depth qualitative interviews with parents who were approached to enroll their children in a clinical trial in order to gain an understanding of the barriers to pediatric clinical trial participation. Twenty-four parents whose children had been offered the opportunity to participate in a clinical trial were interviewed: 19 whose children had participated in at least 1 clinical trial and 5 who had declined participation in any trial. Each study aspect, from the initial explanation of the study to the end of the study, can affect the willingness of parents to consent to the proposed study and future studies. Establishing trust, appropriate timing, a transparent discussion of risks and benefits oriented to the layperson, and providing motivation for children to participate were key factors that impacted parents' decisions. In order for clinical trial accrual to be successful, parents' priorities and considerations must be a central focus, beginning with initial trial design. The recommendations from the parents who participated in this study can be used to support budget allocations that ensure adequate training of study staff and improved staffing on nights and weekends. Studies of parent responses in outpatient settings and additional inpatient settings will provide valuable information on the consent process from the child's and parent's perspectives. Further studies are needed to explore whether implementation of such strategies will result in improved recruitment for pediatric clinical trials.

AutoCPAP initiation at home: optimal trial duration and cost-effectiveness.

PubMed

Bachour, Adel; Virkkala, Jussi T; Maasilta, Paula K

2007-11-01

The duration of automatic computer-controlled continuous positive airway pressure device (autoCPAP) initiation at home varies largely between sleep centers. Our objectives were to evaluate the cost-effectiveness and to find the optimal trial duration. Of the 206 consecutive CPAP-naive patients with obstructive sleep apnea syndrome, who were referred to our hospital, 166 received autoCPAP for a 5-day trial at home. Of the 166 patients, 89 (15 women) showed a successful 5-day autoCPAP trial (normalized oximetry and mask-on time exceeding 4 h/day for at least 4 days). For the first trial day, 88 (53%) patients had normalized oximetry and a mask-on time exceeding 4 h. A 1-day autoCPAP trial EUR 668 was less cost-effective than a 5-day trial EUR 653, with no differences in values of efficient CPAP pressure or residual apnea-hypopnea index (AHI). The systematic requirement of oximetry monitoring raised the cost considerably from EUR 481 to EUR 668. In selected patients with obstructive sleep apnea, the optimal duration for initiating CPAP therapy at home by autoCPAP is 5 days. Although a 1-day trial was sufficient to determine the CPAP pressure requirement, it was not cost-effective and had a high rate of failure.

A Unique Digital Electrocardiographic Repository for the Development of Quantitative Electrocardiography and Cardiac Safety: The Telemetric and Holter ECG Warehouse (THEW)

PubMed Central

Couderc, Jean-Philippe

2010-01-01

The sharing of scientific data reinforces open scientific inquiry; it encourages diversity of analysis and opinion while promoting new research and facilitating the education of next generations of scientists. In this article, we present an initiative for the development of a repository containing continuous electrocardiographic information and their associated clinical information. This information is shared with the worldwide scientific community in order to improve quantitative electrocardiology and cardiac safety. First, we present the objectives of the initiative and its mission. Then, we describe the resources available in this initiative following three components: data, expertise and tools. The Data available in the Telemetric and Holter ECG Warehouse (THEW) includes continuous ECG signals and associated clinical information. The initiative attracted various academic and private partners whom expertise covers a large list of research arenas related to quantitative electrocardiography; their contribution to the THEW promotes cross-fertilization of scientific knowledge, resources, and ideas that will advance the field of quantitative electrocardiography. Finally, the tools of the THEW include software and servers to access and review the data available in the repository. To conclude, the THEW is an initiative developed to benefit the scientific community and to advance the field of quantitative electrocardiography and cardiac safety. It is a new repository designed to complement the existing ones such as Physionet, the AHA-BIH Arrhythmia Database, and the CSE database. The THEW hosts unique datasets from clinical trials and drug safety studies that, so far, were not available to the worldwide scientific community. PMID:20863512

Canadian MSAT field trial program user requirements

NASA Technical Reports Server (NTRS)

Pedersen, Allister

1990-01-01

A wide range of mobile satellite service offerings will be available in late 1993 with the launch of Canada's first satellite devoted almost exclusively to mobile and transportable services. During the last seven years, the Dept. of Communications has been meeting with potential MSAT users in government and the private sector as part of a $20M Communications Trials Program. User trials will be conducted using leased capacity as well as capacity on Canada's MSAT satellite. User requirements are discussed which were identified under the Communications Trials Program. Land, marine, aeronautical, and fixed applications are described from the perspective of the end users. Emphasis is placed on field trials being accomplished using leased capacity such as the marine data trial being implemented by Ultimateast Data Communications, trials using transportable briefcase terminals and additional field trials being considered for implementation with the TMI Mobile Data Service. The pre-MSAT trials that will be conducted using leased capacity are only a limited sample of the overall end user requirements that have been identified to date. Additional end user applications are discussed, along with a summary of user benefits.

Canadian MSAT field trial program user requirements

NASA Astrophysics Data System (ADS)

Pedersen, Allister

A wide range of mobile satellite service offerings will be available in late 1993 with the launch of Canada's first satellite devoted almost exclusively to mobile and transportable services. During the last seven years, the Dept. of Communications has been meeting with potential MSAT users in government and the private sector as part of a $20M Communications Trials Program. User trials will be conducted using leased capacity as well as capacity on Canada's MSAT satellite. User requirements are discussed which were identified under the Communications Trials Program. Land, marine, aeronautical, and fixed applications are described from the perspective of the end users. Emphasis is placed on field trials being accomplished using leased capacity such as the marine data trial being implemented by Ultimateast Data Communications, trials using transportable briefcase terminals and additional field trials being considered for implementation with the TMI Mobile Data Service. The pre-MSAT trials that will be conducted using leased capacity are only a limited sample of the overall end user requirements that have been identified to date. Additional end user applications are discussed, along with a summary of user benefits.

Vessel calibre—a potential MRI biomarker of tumour response in clinical trials

PubMed Central

Emblem, Kyrre E.; Farrar, Christian T.; Gerstner, Elizabeth R.; Batchelor, Tracy T.; Borra, Ronald J. H.; Rosen, Bruce R.; Sorensen, A. Gregory; Jain, Rakesh K.

2015-01-01

Our understanding of the importance of blood vessels and angiogenesis in cancer has increased considerably over the past decades, and the assessment of tumour vessel calibre and structure has become increasingly important for in vivo monitoring of therapeutic response. The preferred method for in vivo imaging of most solid cancers is MRI, and the concept of vessel-calibre MRI has evolved since its initial inception in the early 1990s. Almost a quarter of a century later, unlike traditional contrast-enhanced MRI techniques, vessel-calibre MRI remains widely inaccessible to the general clinical community. The narrow availability of the technique is, in part, attributable to limited awareness and a lack of imaging standardization. Thus, the role of vessel-calibre MRI in early phase clinical trials remains to be determined. By contrast, regulatory approvals of antiangiogenic agents that are not directly cytotoxic have created an urgent need for clinical trials incorporating advanced imaging analyses, going beyond traditional assessments of tumour volume. To this end, we review the field of vessel-calibre MRI and summarize the emerging evidence supporting the use of this technique to monitor response to anticancer therapy. We also discuss the potential use of this biomarker assessment in clinical imaging trials and highlight relevant avenues for future research. PMID:25113840

77 FR 40322 - Oral Rabies Vaccine Trial; Availability of an Environmental Assessment

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-09

...] Oral Rabies Vaccine Trial; Availability of an Environmental Assessment AGENCY: Animal and Plant Health... assessment relative to an oral rabies vaccination field trial in New Hampshire, New York, Ohio, Vermont, and West Virginia. The environmental assessment analyzes the use of an experimental rabies vaccine in field...

Prospective randomised controlled trial of nanocrystalline silver dressing versus plain gauze as the initial post-debridement management of military wounds on wound microbiology and healing.

PubMed

Fries, C A; Ayalew, Y; Penn-Barwell, J G; Porter, K; Jeffery, S L A; Midwinter, M J

2014-07-01

Recent conflicts have been characterised by the use of improvised explosive devices causing devastating injuries, including heavily contaminated wounds requiring meticulous surgical debridement. After being rendered surgical clean, these wounds are dressed and the patient transferred back to the UK for on-going treatment. A dressing that would prevent wounds from becoming colonised during transit would be desirable. The aim of this study was to establish whether using nanocrystalline silver dressings, as an adjunct to the initial debridement, would positively affect wound microbiology and wound healing compared to standard plain gauze dressings. Patients were prospectively randomised to receive either silver dressings, in a nanocrystalline preparation (Acticoat™), or standard of care dressings (plain gauze) following their initial debridement in the field hospital. On repatriation to the UK microbiological swabs were taken from the dressing and the wound, and an odour score recorded. Wounds were followed prospectively and time to wound healing was recorded. Additionally, patient demographic data were recorded, as well as the mechanism of injury and Injury Severity Score. 76 patients were recruited to the trial between February 2010 and February 2012. 39 received current dressings and 37 received the trial dressings. Eleven patients were not swabbed. There was no difference (p=0.1384, Fishers) in the primary outcome measure of wound colonisation between the treatment arm (14/33) and the control arm (20/32). Similarly time to wound healing was not statistically different (p=0.5009, Mann-Whitney). Wounds in the control group were scored as being significantly more malodorous (p=0.002, Mann-Whitney) than those in the treatment arm. This is the first randomised controlled trial to report results from an active theatre of war. Performing research under these conditions poses additional challenges to military clinicians. Meticulous debridement of wounds remains the critical determinant in wound healing and infection and this study did not demonstrate a benefit of nanocrystaline silver dressing in respect to preventing wound colonisation or promoting healing, these dressings do however seem to significantly reduce the unpleasant odour commonly associated with battlefield wounds. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Selenium and selenocysteine: roles in cancer, health and development

PubMed Central

Hatfield, Dolph L.; Tsuji, Petra A.; Carlson, Bradley A.; Gladyshev, Vadim N.

2014-01-01

The many biological and biomedical effects of selenium are relatively unknown outside the selenium field. This fascinating element, initially described as a toxin, was subsequently shown to be essential for health and development. By the mid 1990s, selenium emerged as one of the most promising cancer chemopreventive agents, but subsequent human clinical trials yielded contradictory results. However, basic research on selenium continued to move at a rapid pace elucidating its many roles in health, development, and cancer prevention and promotion. Dietary selenium acts principally through selenoproteins, most of which are oxidoreductases involved in diverse cellular functions. PMID:24485058

Motivational Modulation of Self-Initiated and Externally Triggered Movement Speed Induced by Threat of Shock: Experimental Evidence for Paradoxical Kinesis in Parkinson’s Disease

PubMed Central

McDonald, Louise M.; Griffin, Harry J.; Angeli, Aikaterini; Torkamani, Mariam; Georgiev, Dejan; Jahanshahi, Marjan

2015-01-01

Background Paradoxical kinesis has been observed in bradykinetic people with Parkinson’s disease. Paradoxical kinesis occurs in situations where an individual is strongly motivated or influenced by relevant external cues. Our aim was to induce paradoxical kinesis in the laboratory. We tested whether the motivation of avoiding a mild electric shock was sufficient to induce paradoxical kinesis in externally-triggered and self-initiated conditions in people with Parkinson’s disease tested on medication and in age-matched controls. Methods Participants completed a shock avoidance behavioural paradigm in which half of the trials could result in a mild electric shock if the participant did not move fast enough. Half of the trials of each type were self-initiated and half were externally-triggered. The criterion for avoiding shock was a maximum movement time, adjusted according to each participant’s performance on previous trials using a staircase tracking procedure. Results On trials with threat of shock, both patients with Parkinson’s disease and controls had faster movement times compared to no potential shock trials, in both self-initiated and externally-triggered conditions. The magnitude of improvement of movement time from no potential shock to potential shock trials was positively correlated with anxiety ratings. Conclusions When motivated to avoid mild electric shock, patients with Parkinson’s disease, similar to healthy controls, showed significant speeding of movement execution. This was observed in both self-initiated and externally-triggered versions of the task. Nevertheless, in the ET condition the improvement of reaction times induced by motivation to avoid shocks was greater for the PD patients than controls, highlighting the value of external cues for movement initiation in PD patients. The magnitude of improvement from the no potential shock to the potential shock trials was associated with the threat-induced anxiety. This demonstration of paradoxical kinesis in the laboratory under both self-initiated and externally-triggered conditions has implications for motivational and attentional enhancement of movement speed in Parkinson’s disease. PMID:26284366

Degree of Phosphorus Saturation and Soil Phosphorus Thresholds in an Ultisol Amended with Triple Superphosphate and Phosphate Rocks

PubMed Central

Gikonyo, E. W.; Zaharah, A. R.; Hanafi, M. M.; Anuar, A. R.

2011-01-01

Soil phosphorus (P) release capability could be assessed through the degree of P saturation (DPS). Our main objective was to determine DPS and, hence, P threshold DPS values of an Ultisol treated with triple superphosphate (TSP), Gafsa phosphate rocks (GPR), or Christmas Island phosphate rocks (CIPR), plus or minus manure. P release was determined by the iron oxide—impregnated paper strip (strip P), while DPS was determined from ammonium oxalate—extractable aluminum (Al), iron (Fe), and P. Soils were sampled from a closed incubation study involving soils treated with TSP, GPR, and CIPR at 0–400 mg P kg-1, and a field study where soils were fertilized with the same P sources at 100–300 kg P ha-1 plus or minus manure. The DPS was significantly influenced by P source x P rate, P source x manure (incubated soils), and by P source x P rate x time (field-sampled soils). Incubated soil results indicated that both initial P and total strip P were related to DPS by exponential functions: initial strip P = 1.38exp0.18DPS, R2 = 0.82** and total strip P = 8.01exp0.13DPS, R2 = 0.65**. Initial strip P was linearly related to total P; total P = 2.45, initial P + 8.41, R2 = 0.85**. The threshold DPS value established was about 22% (incubated soil). Field soils had lower DPS values <12% and strip P was related to initial DPS and average DPS in exponential functions: strip P = 2.6exp0.44DPS, R2 = 0.77** and strip P = 1.1DPS2 — 2.4DPS + 6.2, R2 = 0.58**, respectively. The threshold values were both at ≈8% and P release was 11–14 mg P kg-1. Results are evident that DPS can be used to predict P release, but the threshold values are environmentally sensitive; hence, recommendations should be based on field trials. PMID:21805012

Degree of phosphorus saturation and soil phosphorus thresholds in an ultisol amended with triple superphosphate and phosphate rocks.

PubMed

Gikonyo, E W; Zaharah, A R; Hanafi, M M; Anuar, A R

2011-07-28

Soil phosphorus (P) release capability could be assessed through the degree of P saturation (DPS). Our main objective was to determine DPS and, hence, P threshold DPS values of an Ultisol treated with triple superphosphate (TSP), Gafsa phosphate rocks (GPR), or Christmas Island phosphate rocks (CIPR), plus or minus manure. P release was determined by the iron oxide-impregnated paper strip (strip P), while DPS was determined from ammonium oxalate-extractable aluminum (Al), iron (Fe), and P. Soils were sampled from a closed incubation study involving soils treated with TSP, GPR, and CIPR at 0-400 mg P kg-1, and a field study where soils were fertilized with the same P sources at 100-300 kg P ha-1 plus or minus manure. The DPS was significantly influenced by P source x P rate, P source x manure (incubated soils), and by P source x P rate x time (field-sampled soils). Incubated soil results indicated that both initial P and total strip P were related to DPS by exponential functions: initial strip P = 1.38exp0.18DPS, R2 = 0.82** and total strip P = 8.01exp0.13DPS, R2 = 0.65**. Initial strip P was linearly related to total P; total P = 2.45, initial P + 8.41, R2 = 0.85**. The threshold DPS value established was about 22% (incubated soil). Field soils had lower DPS values <12% and strip P was related to initial DPS and average DPS in exponential functions: strip P = 2.6exp0.44DPS, R2 = 0.77** and strip P = 1.1DPS2 ¨C 2.4DPS + 6.2, R2 = 0.58**, respectively. The threshold values were both approximately equal to 8% and P release was 11-14 mg P kg-1. Results are evident that DPS can be used to predict P release, but the threshold values are environmentally sensitive; hence, recommendations should be based on field trials.

The assessment of field trials in GMO research around the world and their possible integration in field trials for variety registration.

PubMed

Slot, M M; van de Wiel, C C M; Kleter, G A; Visser, R G F; Kok, E J

2018-05-04

Most regulations worldwide stipulate that a new genetically modified (GM) crop event has to be compared to its closest non-GM counterpart as a corner stone of the pre-market risk assessment. To this end the GM crop and its comparator should be grown in field trials for a phenotypic comparison as well as for subsequent detailed analysis of the composition of the two crop varieties. A more in-depth globally harmonised approach for the conduct of these field trials is lacking. Only a few countries have formulated detailed protocols for the set-up of GM field trials. In some countries, commercial non-GM reference varieties need to be included in a field study to compile reliable data that indicate the range of natural variation for the compounds tested at the specific location. Detailed analysis of pre-market assessment reports have so far not shown the added value of including these reference varieties in the field trials. In all cases where specific values were found to be outside of the range of the reference varieties, it proved possible to draw conclusions on the part of the pre-market risk assessment that relates to the compositional analysis, on the basis of already available compositional data. With the increasing quality of several databases on compositional data of a growing number of crop species, it seems unlikely that reference varieties will become more important on future occasions. It was furthermore investigated whether this part of the risk assessment can be related to field trial requirements for variety registration with the explicit intention of reducing the data burden on producers of new GM plant varieties. Field trials for variety registration so far include an assessment of phenotypic characteristics that do not cover safety aspects, with the exception of establishment of the glycoalkaloid content in potatoes in the Netherlands and Sweden. It may, however, under certain conditions be relatively easy to exchange data from compositional measurements between variety registration and GM testing procedures, thus laying a foundation for testing the feasibility of combining both pre-market assessment procedures in a single pre-market evaluation path.

CaP CURE Initiatives and Projects

PubMed Central

Soule, Howard R

2003-01-01

CaP CURE was founded in 1993 to help find better treatments and a cure for prostate cancer. By reducing the time and complexity required to apply for funding, and by funding many first-time applicants, CaP CURE has attracted a large number of high-level investigators to the field of prostate cancer research. The organization’s Therapy Consortium meets regularly to address major issues that impede progress in clinical development of new treatments for prostate cancer. CaP CURE has also sponsored an initiative to standardize clinical trial design scenarios for the clinical state of rising prostate-specific antigen and intends to present them to the Food and Drug Administration in partnership with the National Dialogue on Cancer. Finally, CaP CURE’s efforts have resulted in a significant increase in federal funding of prostate cancer research programs. PMID:16986049

Hydrogeology of Basins on Mars

NASA Technical Reports Server (NTRS)

Arvidson, Raymond E.

2001-01-01

This document summarizes the work accomplished under NASA Grant NAG5-3870. Emphasis was put on the development of the FIDO rover, a prototype for the twin-Mers which will be operating on the surface of Mars in 2004, specifically the primary work was the analysis of FIDO field trials. The grantees also analyzed VIKING Lander 1 XRFS and Pathfinder APXS data. Results show that the Viking site chemistry is consistent with an andesite, and the Pathfinder site is consistent with a basaltic andesite. The grantees also worked to demonstrate the capability to simulate annealing methods to apply to the inversion of remote sensing data. They performed an initial analyses of Sojourner engineering telemetry and imaging data. They performed initial analyses of Viking Lander Stereo Images, and of Hematite deposits in Terra Meridiani. They also acquired and analyzed the New Goldstone radar data.

Spatial transformations between superior colliculus visual and motor response fields during head-unrestrained gaze shifts.

PubMed

Sadeh, Morteza; Sajad, Amirsaman; Wang, Hongying; Yan, Xiaogang; Crawford, John Douglas

2015-12-01

We previously reported that visuomotor activity in the superior colliculus (SC)--a key midbrain structure for the generation of rapid eye movements--preferentially encodes target position relative to the eye (Te) during low-latency head-unrestrained gaze shifts (DeSouza et al., 2011). Here, we trained two monkeys to perform head-unrestrained gaze shifts after a variable post-stimulus delay (400-700 ms), to test whether temporally separated SC visual and motor responses show different spatial codes. Target positions, final gaze positions and various frames of reference (eye, head, and space) were dissociated through natural (untrained) trial-to-trial variations in behaviour. 3D eye and head orientations were recorded, and 2D response field data were fitted against multiple models by use of a statistical method reported previously (Keith et al., 2009). Of 60 neurons, 17 showed a visual response, 12 showed a motor response, and 31 showed both visual and motor responses. The combined visual response field population (n = 48) showed a significant preference for Te, which was also preferred in each visual subpopulation. In contrast, the motor response field population (n = 43) showed a preference for final (relative to initial) gaze position models, and the Te model was statistically eliminated in the motor-only population. There was also a significant shift of coding from the visual to motor response within visuomotor neurons. These data confirm that SC response fields are gaze-centred, and show a target-to-gaze transformation between visual and motor responses. Thus, visuomotor transformations can occur between, and even within, neurons within a single frame of reference and brain structure. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Interventions to improve or facilitate linkage to or retention in pre-ART (HIV) care and initiation of ART in low- and middle-income settings – a systematic review

PubMed Central

Govindasamy, Darshini; Meghij, Jamilah; Negussi, Eyerusalem Kebede; Baggaley, Rachel Clare; Ford, Nathan; Kranzer, Katharina

2014-01-01

Introduction Several approaches have been taken to reduce pre-antiretroviral therapy (ART) losses between HIV testing and ART initiation in low- and middle-income countries, but a systematic assessment of the evidence has not yet been undertaken. The aim of this systematic review is to assess the potential for interventions to improve or facilitate linkage to or retention in pre-ART care and initiation of ART in low- and middle-income settings. Methods An electronic search was conducted on Medline, Embase, Global Health, Web of Science and conference databases to identify studies describing interventions aimed at improving linkage to or retention in pre-ART care or initiation of ART. Additional searches were conducted to identify on-going trials on this topic, and experts in the field were contacted. An assessment of the risk of bias was conducted. Interventions were categorized according to key domains in the existing literature. Results A total of 11,129 potentially relevant citations were identified, of which 24 were eligible for inclusion, with the majority (n=21) from sub-Saharan Africa. In addition, 15 on-going trials were identified. The most common interventions described under key domains included: health system interventions (i.e. integration in the setting of antenatal care); patient convenience and accessibility (i.e. point-of-care CD4 count (POC) testing with immediate results, home-based ART initiation); behaviour interventions and peer support (i.e. improved communication, patient referral and education) and incentives (i.e. food support). Several interventions showed favourable outcomes: integration of care and peer supporters increased enrolment into HIV care, medical incentives increased pre-ART retention, POC CD4 testing and food incentives increased completion of ART eligibility screening and ART initiation. Most studies focused on the general adult patient population or pregnant women. The majority of published studies were observational cohort studies, subject to an unclear risk of bias. Conclusions Findings suggest that streamlining services to minimize patient visits, providing adequate medical and peer support, and providing incentives may decrease attrition, but the quality of the current evidence base is low. Few studies have investigated combined interventions, or assessed the impact of interventions across the HIV cascade. Results from on-going trials investigating POC CD4 count testing, patient navigation, rapid ART initiation and mobile phone technology may fill the quality of evidence gap. Further high-quality studies on key population groups are required, with interventions informed by previously reported barriers to care. PMID:25095831

Method matters: Understanding diagnostic reliability in DSM-IV and DSM-5.

PubMed

Chmielewski, Michael; Clark, Lee Anna; Bagby, R Michael; Watson, David

2015-08-01

Diagnostic reliability is essential for the science and practice of psychology, in part because reliability is necessary for validity. Recently, the DSM-5 field trials documented lower diagnostic reliability than past field trials and the general research literature, resulting in substantial criticism of the DSM-5 diagnostic criteria. Rather than indicating specific problems with DSM-5, however, the field trials may have revealed long-standing diagnostic issues that have been hidden due to a reliance on audio/video recordings for estimating reliability. We estimated the reliability of DSM-IV diagnoses using both the standard audio-recording method and the test-retest method used in the DSM-5 field trials, in which different clinicians conduct separate interviews. Psychiatric patients (N = 339) were diagnosed using the SCID-I/P; 218 were diagnosed a second time by an independent interviewer. Diagnostic reliability using the audio-recording method (N = 49) was "good" to "excellent" (M κ = .80) and comparable to the DSM-IV field trials estimates. Reliability using the test-retest method (N = 218) was "poor" to "fair" (M κ = .47) and similar to DSM-5 field-trials' estimates. Despite low test-retest diagnostic reliability, self-reported symptoms were highly stable. Moreover, there was no association between change in self-report and change in diagnostic status. These results demonstrate the influence of method on estimates of diagnostic reliability. (c) 2015 APA, all rights reserved).

National Cancer Institute's Precision Medicine Initiatives for the new National Clinical Trials Network.

PubMed

Abrams, Jeffrey; Conley, Barbara; Mooney, Margaret; Zwiebel, James; Chen, Alice; Welch, John J; Takebe, Naoko; Malik, Shakun; McShane, Lisa; Korn, Edward; Williams, Mickey; Staudt, Louis; Doroshow, James

2014-01-01

The promise of precision medicine will only be fully realized if the research community can adapt its clinical trials methodology to study molecularly characterized tumors instead of the traditional histologic classification. Such trials will depend on adequate tissue collection, availability of quality controlled, high throughput molecular assays, and the ability to screen large numbers of tumors to find those with the desired molecular alterations. The National Cancer Institute's (NCI) new National Clinical Trials Network (NCTN) is well positioned to conduct such trials. The NCTN has the ability to seamlessly perform ethics review, register patients, manage data, and deliver investigational drugs across its many sites including both in cities and rural communities, academic centers, and private practices. The initial set of trials will focus on different questions: (1) Exceptional Responders Initiative-why do a minority of patients with solid tumors or lymphoma respond very well to some drugs even if the majority do not?; (2) NCI MATCH trial-can molecular markers predict response to targeted therapies in patients with advanced cancer resistant to standard treatment?; (3) ALCHEMIST trial-will targeted epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors improve survival for adenocarcinoma of the lung in the adjuvant setting?; and (4) Lung Cancer Master Protocol trial for advanced squamous cell lung cancer-is there an advantage to developing drugs for small subsets of molecularly characterized tumors in a single, multiarm trial design? These studies will hopefully spawn a new era of treatment trials that will carefully select the tumors that may respond best to investigational therapy.

Margins of stability in young adults with traumatic transtibial amputation walking in destabilizing environments✫

PubMed Central

Beltran, Eduardo J.; Dingwell, Jonathan B.; Wilken, Jason M.

2014-01-01

Understanding how lower-limb amputation affects walking stability, specifically in destabilizing environments, is essential for developing effective interventions to prevent falls. This study quantified mediolateral margins of stability (MOS) and MOS sub-components in young individuals with traumatic unilateral transtibial amputation (TTA) and young able-bodied individuals (AB). Thirteen AB and nine TTA completed five 3-minute walking trials in a Computer Assisted Rehabilitation ENvironment (CAREN) system under three each of three test conditions: no perturbations, pseudo-random mediolateral translations of the platform, and pseudo-random mediolateral translations of the visual field. Compared to the unperturbed trials, TTA exhibited increased mean MOS and MOS variability during platform and visual field perturbations (p < 0.010). Also, AB exhibited increased mean MOS during visual field perturbations and increased MOS variability during both platform and visual field perturbations (p < 0.050). During platform perturbations, TTA exhibited significantly greater values than AB for mean MOS (p < 0.050) and MOS variability (p < 0.050); variability of the lateral distance between the center of mass (COM) and base of support at initial contact (p < 0.005); mean and variability of the range of COM motion (p < 0.010); and variability of COM peak velocity (p < 0.050). As determined by mean MOS and MOS variability, young and otherwise healthy individuals with transtibial amputation achieved stability similar to that of their able-bodied counterparts during unperturbed and visually-perturbed walking. However, based on mean and variability of MOS, unilateral transtibial amputation was shown to have affected walking stability during platform perturbations. PMID:24444777

Field trials of 100G and beyond: an operator's point of view

NASA Astrophysics Data System (ADS)

Vorbeck, S.; Schneiders, M.; Weiershausen, W.; Mayer, H.; Schippel, A.; Wagner, P.; Ehrhardt, A.; Braun, R.; Breuer, D.; Drafz, U.; Fritzsche, D.

2011-01-01

In this article we present a summary of the latest 100 Gbps field trials in the network of Deutsche Telekom AG with industry partners. We cover a brown field approach as alien wavelength on existing systems, a green field high speed overlay network approach and a high speed interface router-router coupling.

Mississippi exploration field trials using microbial, radiometrics, free soil gas, and other techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moody, J.S.; Brown, L.R.; Thieling, S.C.

1995-12-31

The Mississippi Office of Geology has conducted field trials using the surface exploration techniques of geomicrobial, radiometrics, and free soil gas. The objective of these trials is to determine if Mississippi oil and gas fields have surface hydrocarbon expression resulting from vertical microseepage migration. Six fields have been surveyed ranging in depth from 3,330 ft to 18,500 ft. The fields differ in trapping styles and hydrocarbon type. The results so far indicate that these fields do have a surface expression and that geomicrobial analysis as well as radiometrics and free soil gas can detect hydrocarbon microseepage from pressurized reservoirs. Allmore » three exploration techniques located the reservoirs independent of depth, hydrocarbon type, or trapping style.« less

Feasibility and acceptability of the DSM-5 Field Trial procedures in the Johns Hopkins Community Psychiatry Programs†

PubMed Central

Clarke, Diana E.; Wilcox, Holly C.; Miller, Leslie; Cullen, Bernadette; Gerring, Joan; Greiner, Lisa H.; Newcomer, Alison; Mckitty, Mellisha V.; Regier, Darrel A.; Narrow, William E.

2014-01-01

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) contains criteria for psychiatric diagnoses that reflect advances in the science and conceptualization of mental disorders and address the needs of clinicians. DSM-5 also recommends research on dimensional measures of cross-cutting symptoms and diagnostic severity, which are expected to better capture patients’ experiences with mental disorders. Prior to its May 2013 release, the American Psychiatric Association (APA) conducted field trials to examine the feasibility, clinical utility, reliability, and where possible, the validity of proposed DSM-5 diagnostic criteria and dimensional measures. The methods and measures proposed for the DSM-5 field trials were pilot tested in adult and child/adolescent clinical samples, with the goal to identify and correct design and procedural problems with the proposed methods before resources were expended for the larger DSM-5 Field Trials. Results allowed for the refinement of the protocols, procedures, and measures, which facilitated recruitment, implementation, and completion of the DSM-5 Field Trials. These results highlight the benefits of pilot studies in planning large multisite studies. PMID:24615761

2017 Cardiovascular and Stroke Endpoint Definitions for Clinical Trials.

PubMed

Hicks, Karen A; Mahaffey, Kenneth W; Mehran, Roxana; Nissen, Steven E; Wiviott, Stephen D; Dunn, Billy; Solomon, Scott D; Marler, John R; Teerlink, John R; Farb, Andrew; Morrow, David A; Targum, Shari L; Sila, Cathy A; Hai, Mary T Thanh; Jaff, Michael R; Joffe, Hylton V; Cutlip, Donald E; Desai, Akshay S; Lewis, Eldrin F; Gibson, C Michael; Landray, Martin J; Lincoff, A Michael; White, Christopher J; Brooks, Steven S; Rosenfield, Kenneth; Domanski, Michael J; Lansky, Alexandra J; McMurray, John J V; Tcheng, James E; Steinhubl, Steven R; Burton, Paul; Mauri, Laura; O'Connor, Christopher M; Pfeffer, Marc A; Hung, H M James; Stockbridge, Norman L; Chaitman, Bernard R; Temple, Robert J

2018-02-27

This publication describes uniform definitions for cardiovascular and stroke outcomes developed by the Standardized Data Collection for Cardiovascular Trials Initiative and the US Food and Drug Administration (FDA). The FDA established the Standardized Data Collection for Cardiovascular Trials Initiative in 2009 to simplify the design and conduct of clinical trials intended to support marketing applications. The writing committee recognizes that these definitions may be used in other types of clinical trials and clinical care processes where appropriate. Use of these definitions at the FDA has enhanced the ability to aggregate data within and across medical product development programs, conduct meta-analyses to evaluate cardiovascular safety, integrate data from multiple trials, and compare effectiveness of drugs and devices. Further study is needed to determine whether prospective data collection using these common definitions improves the design, conduct, and interpretability of the results of clinical trials. © 2018 American Heart Association, Inc.

Lung-MAP Launches: First Precision Medicine Trial From National Clinical Trials Network

Cancer.gov

A unique public-private collaboration today announced the initiation of the Lung Cancer Master Protocol (Lung-MAP) trial, a multi-drug, multi-arm, biomarker-driven clinical trial for patients with advanced squamous cell lung cancer. Squamous cell carcinom

Longitudinal Vision-Related Quality of Life for Patients with Noninfectious Uveitis Treated with Fluocinolone Acetonide Implant or Systemic Corticosteroid Therapy.

PubMed

Sugar, Elizabeth A; Venugopal, Vidya; Thorne, Jennifer E; Frick, Kevin D; Holland, Gary N; Wang, Robert C; Almanzor, Robert; Jabs, Douglas A; Holbrook, Janet T

2017-11-01

To evaluate longitudinal vision-related quality of life (VRQoL) in patients with noninfectious uveitis. Cohort study using randomized controlled trial data. Patients with active or recently active intermediate uveitis, posterior uveitis, or panuveitis enrolled in the Multicenter Steroid Treatment Trial and Follow-up Study. Data from the 25-item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) for the first 3 years after randomization were evaluated semiannually. Analyses were stratified by assigned treatment (129 implants vs. 126 systemic therapies) because of substantial differences in the trajectories of VRQoL. The impact of baseline measurements of visual function (visual acuity and visual field), demographics, and disease characteristics was assessed using generalized estimating equations. Primary outcome was the NEI-VFQ-25 composite score over 3 years after randomization. Individuals in both treatment groups showed similar improvement in NEI-VFQ-25 scores after 3 years of follow-up (implant: 11.9 points; 95% confidence interval [CI], 8.6-15.2; P < 0.001; systemic: 9.0 points; 95% CI, 5.6-12.3; P < 0.001; P = 0.21 for interaction). Individuals in the implant group showed a substantial improvement during the first 6 months followed by stable scores, whereas individuals in the systemic group showed a steady improvement over the course of follow-up. Worse initial visual acuity and visual fields were associated with lower initial NEI-VFQ-25 scores for both treatment groups. In the systemic group, these differences were maintained throughout follow-up. In the implant group, individuals with initial visual acuity worse than 20/40 showed additional improvement in NEI-VFQ-25 score to come within -7 points (95% CI, -15.0 to 0.9) of those with visual acuity 20/40 or better initially, a clinically meaningful but not statistically significant difference (P = 0.081). Results based on sensitivity analyses showed similar patterns. Both treatment groups demonstrated significant improvements in NEI-VFQ-25 scores; however, the improvement was immediate for the implant group as opposed to gradual for the systemic group. Poorer visual function was associated significantly with initial differences in NEI-VFQ-25 scores. However, only individuals in the implant group with poor visual acuity were able to overcome their initial deficits by the end of 3 years. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Protocol for a randomised controlled trial of VAsopressin versus Noradrenaline as Initial therapy in Septic sHock (VANISH)

PubMed Central

Gordon, Anthony C; Mason, Alexina J; Perkins, Gavin D; Ashby, Deborah; Brett, Stephen J

2014-01-01

Introduction Vasopressin is an alternative vasopressor in the management of septic shock. It spares catecholamine use but whether it improves outcome remains uncertain. Current evidence suggests that it may be most effective if used early and possibly in conjunction with corticosteroids. This trial will compare vasopressin to noradrenaline as initial vasopressor in the management of adult septic shock and investigate whether there is an interaction of vasopressin with corticosteroids. Methods and analysis This is a multicentre, factorial (2×2), randomised, double-blind, placebo-controlled trial. 412 patients will be recruited from multiple UK intensive care units and randomised to receive vasopressin (0–0.06 U/min) or noradrenaline (0–12 µg/min) as a continuous intravenous infusion as initial vasopressor therapy. If maximum infusion rates of this first study drug are reached, the patient will be treated with either hydrocortisone (initially 50 mg intravenous bolus six-hourly) or placebo, before additional open-label catecholamine vasopressors are prescribed. The primary outcome of the trial will be the difference in renal failure-free days between treatment groups. Secondary outcomes include need for renal replacement therapy, survival rates, other organ failures and resource utilisation. Ethics and dissemination The trial protocol and information sheets have received a favourable opinion from the Oxford A Research Ethics Committee (12/SC/0014). There is an independent Data Monitoring and Ethics Committee and independent membership of the Trial Steering Committee including patient and public involvement. The trial results will be published in peer-reviewed journals and presented at national and international scientific meetings. Trial registration number: ISRCTN 20769191 and EudraCT 2011-005363-24. PMID:24993769

Field design factors affecting the precision of ryegrass forage yield estimation

USDA-ARS?s Scientific Manuscript database

Field-based agronomic and genetic research relies heavily on the data generated from field evaluations. Therefore, it is imperative to optimize the precision and accuracy of yield estimates in cultivar evaluation trials to make reliable selections. Experimental error in yield trials is sensitive to ...

Quality of life in newly diagnosed glaucoma patients : The Collaborative Initial Glaucoma Treatment Study.

PubMed

Janz, N K; Wren, P A; Lichter, P R; Musch, D C; Gillespie, B W; Guire, K E

2001-05-01

The Collaborative Initial Glaucoma Treatment Study (CIGTS) was designed to determine whether patients with newly diagnosed open-angle glaucoma are better treated initially by medicine or immediate filtering surgery. This paper describes the quality-of-life (QOL) measurement approach, instruments included, and the CIGTS participants' QOL findings at the time of diagnosis. Baseline results from a randomized, controlled clinical trial. Six hundred seven patients from 14 clinical centers were enrolled. Patients randomized to initial medication received a stepped medical regimen (n = 307). Those randomized to initial surgery underwent a trabeculectomy (n = 300). The baseline interview was conducted before treatment initiation. All baseline and posttreatment QOL assessments were conducted by telephone from a centralized interviewing center. The primary outcome measure described in this paper was QOL. The QOL instrument is multidimensional and incorporates both disease-specific and generic measures, including the Visual Activities Questionnaire, Sickness Impact Profile, and a Symptom and Health Problem CHECKLIST: The correlations between QOL measures and clinical outcomes were in the expected direction, but relatively weak. At initial diagnosis, difficulty with bright lights and with light and dark adaptation were the most frequently reported symptoms related to visual function, whereas visual distortion was the most bothersome. Approximately half of the patients reported at least some worry or concern about the possibility of blindness. Within the Visual Activities Questionnaire, higher scores on the Peripheral Vision subscale were associated with more field loss (P < 0.01). In regression analyses controlling for sociodemographics and nonocular comorbidities, increased visual field loss was significantly associated with higher dysfunction among five disease-specific QOL measures (P < 0.05). Newly diagnosed glaucoma patients reported experiencing some visual function symptoms at the time of diagnosis that would not be intuitively expected based on clinical testing. Some discussion about the association between clinical presentation and worry about blindness may reduce unnecessary concern. These results provide the basis for long-term comparisons of the QOL effects of initial medical and surgical treatment for open-angle glaucoma.

Defining precision: The precision medicine initiative trials NCI-MPACT and NCI-MATCH.

PubMed

Coyne, Geraldine O'Sullivan; Takebe, Naoko; Chen, Alice P

"Precision" trials, using rationally incorporated biomarker targets and molecularly selective anticancer agents, have become of great interest to both patients and their physicians. In the endeavor to test the cornerstone premise of precision oncotherapy, that is, determining if modulating a specific molecular aberration in a patient's tumor with a correspondingly specific therapeutic agent improves clinical outcomes, the design of clinical trials with embedded genomic characterization platforms which guide therapy are an increasing challenge. The National Cancer Institute Precision Medicine Initiative is an unprecedented large interdisciplinary collaborative effort to conceptualize and test the feasibility of trials incorporating sequencing platforms and large-scale bioinformatics processing that are not currently uniformly available to patients. National Cancer Institute-Molecular Profiling-based Assignment of Cancer Therapy and National Cancer Institute-Molecular Analysis for Therapy Choice are 2 genomic to phenotypic trials under this National Cancer Institute initiative, where treatment is selected according to predetermined genetic alterations detected using next-generation sequencing technology across a broad range of tumor types. In this article, we discuss the objectives and trial designs that have enabled the public-private partnerships required to complete the scale of both trials, as well as interim trial updates and strategic considerations that have driven data analysis and targeted therapy assignment, with the intent of elucidating further the benefits of this treatment approach for patients. Copyright © 2017. Published by Elsevier Inc.

A critical review of clinical trials in systemic lupus erythematosus

PubMed Central

Mahieu, Mary A.; Strand, Vibeke; Simon, Lee S.; Lipsky, Peter E.; Ramsey-Goldman, Rosalind

2016-01-01

One challenge in caring for patients with systemic lupus erythematosus (SLE) is a paucity of approved therapeutics for treatment of the diverse disease manifestations. In the last 60 years, only one drug, belimumab, has been approved for SLE treatment. Critical evaluation of investigator initiated and pharma-sponsored randomized controlled trials (RCTs) highlights barriers to successful drug development in SLE, including disease heterogeneity, inadequate trial size or duration, insufficient dose finding before initiation of large trials, handling of background medications, and choice of primary endpoint. Herein we examine lessons learned from landmark SLE RCTs and subsequent advances in trial design, as well as discuss efforts to address limitations in current SLE outcome measures that will improve detection of true therapeutic responses in future RCTs. PMID:27497257

AccrualNet: Addressing Low Accrual Via a Knowledge-Based, Community of Practice Platform

PubMed Central

Massett, Holly A.; Parreco, Linda K.; Padberg, Rose Mary; Richmond, Ellen S.; Rienzo, Marie E.; Leonard, Colleen E. Ryan; Quesenbery, Whitney; Killiam, H. William; Johnson, Lenora E.; Dilts, David M.

2011-01-01

Purpose: Present the design and initial evaluation of a unique, Web-enabled platform for the development of a community of practice around issues of oncology clinical trial accrual. Methods: The National Cancer Institute (NCI) conducted research with oncology professionals to identify unmet clinical trial accrual needs in the field. In response, a comprehensive platform for accrual resources, AccrualNet, was created by using an agile development process, storyboarding, and user testing. Literature and resource searches identified relevant content to populate the site. Descriptive statistics were tracked for resource and site usage. Use cases were defined to support implementation. Results: AccrualNet has five levels: (1) clinical trial macrostages (prestudy, active study, and poststudy); (2) substages (developing a protocol, selecting a trial, preparing to open, enrolling patients, managing the trial, retaining participants, and lessons learned); (3) strategies for each substage; (4) multiple activities for each strategy; and (5) multiple resources for each activity. Since its launch, AccrualNet has had more than 45,000 page views, with the Tools & Resources, Conversations, and Training sections being the most viewed. Total resources have increased 69%, to 496 items. Analysis of articles in the site reveals that 22% are from two journals and 46% of the journals supplied a single article. To date, there are 29 conversations with 43 posts. Four use cases are discussed. Conclusion: AccrualNet represents a unique, centralized comprehensive-solution platform to systematically capture accrual knowledge for all stages of a clinical trial. It is designed to foster a community of practice by encouraging users to share additional strategies, resources, and ideas. PMID:22379429

AccrualNet: Addressing Low Accrual Via a Knowledge-Based, Community of Practice Platform.

PubMed

Massett, Holly A; Parreco, Linda K; Padberg, Rose Mary; Richmond, Ellen S; Rienzo, Marie E; Leonard, Colleen E Ryan; Quesenbery, Whitney; Killiam, H William; Johnson, Lenora E; Dilts, David M

2011-11-01

Present the design and initial evaluation of a unique, Web-enabled platform for the development of a community of practice around issues of oncology clinical trial accrual. The National Cancer Institute (NCI) conducted research with oncology professionals to identify unmet clinical trial accrual needs in the field. In response, a comprehensive platform for accrual resources, AccrualNet, was created by using an agile development process, storyboarding, and user testing. Literature and resource searches identified relevant content to populate the site. Descriptive statistics were tracked for resource and site usage. Use cases were defined to support implementation. ACCRUALNET HAS FIVE LEVELS: (1) clinical trial macrostages (prestudy, active study, and poststudy); (2) substages (developing a protocol, selecting a trial, preparing to open, enrolling patients, managing the trial, retaining participants, and lessons learned); (3) strategies for each substage; (4) multiple activities for each strategy; and (5) multiple resources for each activity. Since its launch, AccrualNet has had more than 45,000 page views, with the Tools & Resources, Conversations, and Training sections being the most viewed. Total resources have increased 69%, to 496 items. Analysis of articles in the site reveals that 22% are from two journals and 46% of the journals supplied a single article. To date, there are 29 conversations with 43 posts. Four use cases are discussed. AccrualNet represents a unique, centralized comprehensive-solution platform to systematically capture accrual knowledge for all stages of a clinical trial. It is designed to foster a community of practice by encouraging users to share additional strategies, resources, and ideas.

The use of in vivo thermoluminescent dosimeters in the quality assurance programme for the START breast fractionation trial.

PubMed

Venables, Karen; Miles, Elizabeth A; Aird, Edwin G A; Hoskin, Peter J

2004-06-01

The use of in vivo dosimetry for patient measurement is recommended in many publications. It provides an additional check to verify that the dose delivered to the patient corresponds to the prescribed dose. In the context of a clinical trial investigating the effects of different fractionation regimens, it is imperative that the dose given is that prescribed to ensure that noise in the data between centres does not mask the results of the trial. The methodology for in vivo measurement in a clinical trial of breast radiotherapy was developed and verified. A cohort of patients in the STAndardisation of breast RadioTherapy (START) trial was monitored using postal thermoluminescent dosimeters chips (TLD). All TLD were processed and analysed at Mount Vernon Hospital. Patients for in vivo measurements were identified at randomisation as a random 1 in 9 samples for the first 2500 patients randomised (282 TLD) increasing to 1 in 3 thereafter. The TLD were left in place for the duration of the tangential field treatment and thus a composite entrance and exit dose was recorded. TLD measurements were performed on 429 patients from 33 hospitals. The average ratio of dose measured using TLD to that prescribed was 0.99+/-0.04. Eight patients had initial measurements more than 10% different to the prescribed dose. The mean TLD results for a given centre correlated well with dose measurements performed using an ionisation chamber in a breast shaped phantom at that centre as part of the START trial audit. Thermoluminescence dosimetry has provided useful quality assurance information on the doses received by patients in centres participating in the START trial.

Multimedia communications and services for the healthcare community

NASA Astrophysics Data System (ADS)

Robinson, James M.

1994-11-01

The NYNEX Media Broadband Service Trials in Boston examined the use of several multiple media applications from healthcare in conjunction with high speed fiber optic networks. As part of these trials, NYNEX developed a network-based software technology that simplifies and coordinates the delivery of complex voice, data, image, and video information. This permits two or more users to interact and collaborate with one another while sharing, displaying, and manipulating various media types. Different medical applications were trialed at four of Boston's major hospitals, ranging from teleradiology (which tested the quality of the diagnostic images and the need to collaborate) to telecardiology (which displayed diagnostic quality digital movies played in synchronicity). These trials allowed NYNEX to uniquely witness the needs and opportunities in the healthcare community for broadband communications with the necessary control capabilities and simplified user interface. As a result of the success of the initial trials, NYNEX has created a new business unit, Media Communications Services (MCS), to deliver a service offering based on this capability. New England Medical Center, as one of the initial trial sites, was chosen as a beta trial candidate, and wanted to further its previous work in telecardiology as well as telepsychiatry applications. Initial and subsequent deployments have been completed, and medical use is in progress.

Managing the rate of increase in average co-ancestry in a rolling front tree breeding strategy.

PubMed

Kerr, R J; McRae, T A; Dutkowski, G W; Tier, B

2015-04-01

In breeding forest trees, as for livestock, the goal is to capture as much genetic gain as possible for the breeding objective, while limiting long- and short-term inbreeding. The Southern Tree Breeding Association (STBA) is responsible for breeding Australia's two main commercial forest tree species and has adopted algorithms and methods commonly used in animal breeding to achieve this balance. Discrete generation breeding is the norm for most tree breeding programmes. However, the STBA uses an overlapping generation strategy, with a new stream of breeding initiated each year. A feature of the species bred by the STBA (Pinus radiata and Eucalyptus globulus) is the long interval (up to 7 years) between when an individual is mated and when its progeny is first assessed in field trials and performance data included in the national performance database. Mate selection methods must therefore recognize the large pool of unmeasured progeny generated over recent years of crossing. In addition, the substantial delay between when an individual is selected in a field trial and when it is clonally copied into a mating facility (breeding arboretum) means that selection and mating must occur as a two-step process. In this article, we describe modifications to preselection and mate selection algorithms that allow unmeasured progeny (juveniles) to be recognized. We also demonstrate that the addition of hypothetical new progeny to the juvenile pool is important for computing the increase in average co-ancestry in the population. Methods outlined in this article may have relevance to animal breeding programmes where between mating and progeny measurement, new rounds of mating are initiated. © 2015 Blackwell Verlag GmbH.

Effects of water chemistry on arsenic removal from drinking water by electrocoagulation.

PubMed

Wan, Wei; Pepping, Troy J; Banerji, Tuhin; Chaudhari, Sanjeev; Giammar, Daniel E

2011-01-01

Exposure to arsenic through drinking water poses a threat to human health. Electrocoagulation is a water treatment technology that involves electrolytic oxidation of anode materials and in-situ generation of coagulant. The electrochemical generation of coagulant is an alternative to using chemical coagulants, and the process can also oxidize As(III) to As(V). Batch electrocoagulation experiments were performed in the laboratory using iron electrodes. The experiments quantified the effects of pH, initial arsenic concentration and oxidation state, and concentrations of dissolved phosphate, silica and sulfate on the rate and extent of arsenic removal. The iron generated during electrocoagulation precipitated as lepidocrocite (γ-FeOOH), except when dissolved silica was present, and arsenic was removed by adsorption to the lepidocrocite. Arsenic removal was slower at higher pH. When solutions initially contained As(III), a portion of the As(III) was oxidized to As(V) during electrocoagulation. As(V) removal was faster than As(III) removal. The presence of 1 and 4 mg/L phosphate inhibited arsenic removal, while the presence of 5 and 20 mg/L silica or 10 and 50 mg/L sulfate had no significant effect on arsenic removal. For most conditions examined in this study, over 99.9% arsenic removal efficiency was achieved. Electrocoagulation was also highly effective at removing arsenic from drinking water in field trials conducted in a village in Eastern India. By using operation times long enough to produce sufficient iron oxide for removal of both phosphate and arsenate, the performance of the systems in field trials was not inhibited by high phosphate concentrations. Copyright © 2010 Elsevier Ltd. All rights reserved.

Field Trial of Methoxyflurane, Nitrous Oxide, and Trichloroethylene as Obstetric Analgesics

PubMed Central

Rosen, M.; Mushin, W. W.; Jones, P. L.; Jones, E. V.

1969-01-01

In a field trial of 1,257 patients receiving methoxyflurane, trichloroethylene, and nitrous-oxide/oxygen for the relief of pain in labour methoxyflurane has been shown to have certain advantages which support its use in midwifery practice. The trial confirms our objective method for screening an inhalational agent as an obstetric analgesic. PMID:4895340

First field trials with fungi against Anoplophora glabripennis

Treesearch

Thomas Dubois; Ann Hajek; Hu Jiafu; Zengzhi Li

2003-01-01

We have been evaluating the use of entomopathogenic fungi against A. glabripennis; so far, 20 strains have been isolated belonging to three species, 14 strains have been tested in the laboratory, five strains have been evaluated in caged field trials and two strains have been tested in the open field.

Lost Hills Field Trial - incorporating new technology for resevoir management

NASA Technical Reports Server (NTRS)

Fielding, E. J.; Brink, J. L.; Patzek, T. W.; Silin, D. B.

2002-01-01

This paper will discuss how Chevron U.S.A. Production Company is implementing a field trial that will use Supervisory Control and Data Acquisition (SCADA)on injection wells, in conjunction with satellite images to measure ground elevation changes, to perform real-time resevoir management in the Lost Hills Field.

Randomised comparison of the effectiveness of the laryngeal mask airway supreme, i-gel and current practice in the initial airway management of prehospital cardiac arrest (REVIVE-Airways): a feasibility study research protocol.

PubMed

Benger, Jonathan Richard; Voss, Sarah; Coates, David; Greenwood, Rosemary; Nolan, Jerry; Rawstorne, Steven; Rhys, Megan; Thomas, Matthew

2013-01-01

Effective cardiopulmonary resuscitation with appropriate airway management improves outcomes following out-of-hospital cardiac arrest (OHCA). Historically, tracheal intubation has been accepted as the optimal form of OHCA airway management in the UK. The Joint Royal Colleges Ambulance Liaison Committee recently concluded that newer supraglottic airway devices (SADs) are safe and effective devices for hospital procedures and that their use in OHCA should be investigated. This study will address an identified gap in current knowledge by assessing whether it is feasible to use a cluster randomised design to compare SADs with current practice, and also to each other, during OHCA. The primary objective of this study is to assess the feasibility of a cluster randomised trial to compare the ventilation success of two newer SADs: the i-gel and the laryngeal mask airway supreme to usual practice during the initial airway management of OHCA. The secondary objectives are to collect data on ventilation success, further airway interventions required, loss of a previously established airway during transport, airway management on arrival at hospital (or termination of the resuscitation attempt), initial resuscitation success, survival to intensive care admission, survival to hospital discharge and patient outcome at 3 months. Ambulance paramedics will be randomly allocated to one of the three methods of airway management. Adults in medical OHCA attended by a trial paramedic will be eligible for the study. Approval for the study has been obtained from a National Health Service Research Ethics Committee with authority to review proposals for trials of a medical device in incapacitated adults. The results will be made publicly available on an open access website, and we will publish the findings in appropriate journals and present them at national and international conferences relevant to the subject field. ISRCTN: 18528625.

The challenges and opportunities of conducting a clinical trial in a low resource setting: the case of the Cameroon mobile phone SMS (CAMPS) trial, an investigator initiated trial.

PubMed

Mbuagbaw, Lawrence; Thabane, Lehana; Ongolo-Zogo, Pierre; Lang, Trudie

2011-06-09

Conducting clinical trials in developing countries often presents significant ethical, organisational, cultural and infrastructural challenges to researchers, pharmaceutical companies, sponsors and regulatory bodies. Globally, these regions are under-represented in research, yet this population stands to gain more from research in these settings as the burdens on health are greater than those in developed resourceful countries. However, developing countries also offer an attractive setting for clinical trials because they often have larger treatment naive populations with higher incidence rates of disease and more advanced stages. These factors can present a reduction in costs and time required to recruit patients. So, balance needs to be found where research can be encouraged and supported in order to bring maximum public health benefits to these communities. The difficulties with such trials arise from problems with obtaining valid informed consent, ethical compensation mechanisms for extremely poor populations, poor health infrastructure and considerable socio-economic and cultural divides. Ethical concerns with trials in developing countries have received attention, even though many other non-ethical issues may arise. Local investigator initiated trials also face a variety of difficulties that have not been adequately reported in literature. This paper uses the example of the Cameroon Mobile Phone SMS trial to describe in detail, the specific difficulties encountered in an investigator-initiated trial in a developing country. It highlights administrative, ethical, financial and staff related issues, proposes solutions and gives a list of additional documentation to ease the organisational process.

Antifungal genes expressed in transgenic pea (Pisum sativum L.) do not affect root colonization of arbuscular mycorrhizae fungi.

PubMed

Kahlon, Jagroop Gill; Jacobsen, Hans-Jörg; Cahill, James F; Hall, Linda M

2017-10-01

Genetically modified crops have raised concerns about unintended consequences on non-target organisms including beneficial soil associates. Pea transformed with four antifungal genes 1-3 β glucanase, endochitinase, polygalacturonase-inhibiting proteins, and stilbene synthase is currently under field-testing for efficacy against fungal diseases in Canada. Transgenes had lower expression in the roots than leaves in greenhouse experiment. To determine the impact of disease-tolerant pea or gene products on colonization by non-target arbuscular mycorrhizae and nodulation by rhizobium, a field trial was established. Transgene insertion, as single gene or stacked genes, did not alter root colonization by arbuscular mycorrhiza fungus (AMF) or root nodulation by rhizobium inoculation in the field. We found no effect of transgenes on the plant growth and performance although, having a dual inoculant with both AMF and rhizobium yielded higher fresh weight shoot-to-root ratio in all the lines tested. This initial risk assessment of transgenic peas expressing antifungal genes showed no deleterious effect on non-target organisms.

CATCH: Child and Adolescent Trial for Cardiovascular Health. [Multimedia.

ERIC Educational Resources Information Center

National Heart, Lung, and Blood Inst. (DHHS/NIH), Bethesda, MD.

The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health has launched an initiative called the Cardiovascular Health Promotion Project to teach heart-healthy habits to children. One of the programs developed by this initiative, CATCH, the Child and Adolescent Trial for Cardiovascular Health, is the largest…

Standard versus accelerated initiation of renal replacement therapy in acute kidney injury (STARRT-AKI): study protocol for a randomized controlled trial.

PubMed

Smith, Orla M; Wald, Ron; Adhikari, Neill K J; Pope, Karen; Weir, Matthew A; Bagshaw, Sean M

2013-10-05

Acute kidney injury is a common and devastating complication of critical illness, for which renal replacement therapy is frequently needed to manage severe cases. While a recent systematic review suggested that "earlier" initiation of renal replacement therapy improves survival, completed trials are limited due to small size, single-centre status, and use of variable definitions to define "early" renal replacement therapy initiation. This is an open-label pilot randomized controlled trial. One hundred critically ill patients with severe acute kidney injury will be randomly allocated 1:1 to receive "accelerated" initiation of renal replacement therapy or "standard" initiation at 12 centers across Canada. In the accelerated arm, participants will have a venous catheter placed and renal replacement therapy will be initiated within 12 hours of fulfilling eligibility. In the standard initiation arm, participants will be monitored over 7 days to identify indications for renal replacement therapy. For participants in the standard arm with persistent acute kidney injury, defined as a serum creatinine not declining >50% from the value at the time of eligibility, the initiation of RRT will be discouraged unless one or more of the following criteria are fulfilled: serum potassium ≥6.0 mmol/L; serum bicarbonate ≤10 mmol/L; severe respiratory failure (PaO₂/FiO₂<200) or persisting acute kidney injury for ≥72 hours after fulfilling eligibility. The inclusion criteria are designed to identify a population of critically ill adults with severe acute kidney injury who are likely to need renal replacement therapy during their hospitalization, but not immediately. The primary outcome is protocol adherence (>90%). Secondary outcomes include measures of feasibility (proportion of eligible patients enrolled in the trial, proportion of enrolled patients followed to 90 days for assessment of vital status and the need for renal replacement therapy) and safety (occurrence of adverse events). The optimal timing of renal replacement therapy initiation in patients with severe acute kidney injury remains uncertain, representing an important knowledge gap and a priority for high-quality research. This pilot trial is necessary to establish protocol feasibility, confirm the safety of participants and obtain estimated events rates for design of a large definitive trial. NCT01557361.

Effects of Dehydration on Cricket Specific Skill Performance in Hot and Humid Conditions.

PubMed

Gamage, Janaka P; De Silva, Angela P; Nalliah, Arjan K; Galloway, Stuart D R

2016-12-01

The aim of the current study was to assess the effects of dehydration on cricket specific motor skill performance among fast-bowlers, fielders, and batsmen playing in a hot and humid environment. 10 fast-bowlers, 12 fielders and 8 batsmen participated in two field trials conducted 7 days apart: a fluid provision trial (FP) and a fluid restriction trial (FR). Each trial consisted of a 2-hr standardized training session and pretraining and posttraining skill performance assessments. Bowling speed and accuracy (line and length), throwing speed and accuracy (overarm, sidearm and underarm) and timed running between wickets (1, 2, and 3 runs) was assessed pre to posttraining in each trial. Mass loss was 0.6 ± 0.3 kg (0.9 ± 0.5%) in FP, and 2.6 ± 0.5kg (3.7 ± 0.8%) in FR trials. Maintaining mass within 1% of initial values did not cause any significant skill performance decline. However, the dehydration on the FR trial induced a significant time and trial effect for bowling speed by 1.0 ± 0.8% reduction (0.3 ± 0.8% reduction in FP trial; p < .01) and 19.8 ± 17.3% reduction in bowling accuracy for line (3.6 ± 14.2% reduction in FP trial; p < .01), but no effect on bowling length. A significant decline was noted in the FR trial for throwing speed for overarm (6.6 ± 4.1%; p < .01; 1.6 ± 3.4% reduction in FP trial) and sidearm (4.1 ± 2.3%; p < .01; 0.6 ± 4.7% increase in FP trial) techniques, and for throwing accuracy for overarm (14.2 ± 16.3%; p < .01; 0.8 ± 24.2% increase in FP trial) and sidearm (22.3 ± 13.3%; p < .05; 3.2 ± 34.9% reduction in FP trial) techniques. Batsmen demonstrated significant performance drop in making three runs (0.8 ± 1.2% increase in time in FP trial and 2.2 ± 1.7% increase in time in FR trial; p < .01). Moderate-severe dehydration of 3.7% body mass loss significantly impairs motor skill performance among cricketers, particularly bowlers and fielders, playing in hot and humid conditions. Fluid ingestion strategies maintaining mass loss within 1% prevented a decline in skill performance.

[Basic principles, planning and implementation of non-commercial clinical trials].

PubMed

Finger, R P; Coch, C; Coenen, M; Mengel, M; Hartmann, G; Holz, F G

2011-01-01

The proof of a drug's efficacy in randomized controlled trials is fundamental to therapeutic concepts determined by evidence-based medicine. Clinical trials according to the German Medicinal Products Act are performed by the pharmaceutical industry as company-sponsored trials (CST) driven by commercial interests or by non-commercial facilities as investigator-initiated trials (IIT), typically implemented by University Hospitals. In areas with no commercial interest, IITs are the driving force that generate scientific progress leading to treatment optimization. Therefore, non-commercial or investigator-initiated clinical trials are indispensable for improving medical care. To ensure the safety of trial participants and the quality of the data obtained, clinical trials are controlled by many legal regulations and internationally accepted quality standards. Therefore implementation of a clinical trial requires profound knowledge, qualified personnel, appropriate infrastructure, and substantial financial resources. In IITs unlike CSTs this has to be accomplished by the University without the assistance of the pharmaceutical industry. Since teaching of skills needed to perform clinical trials is still largely neglected in medical school and during residency this review addresses the (in clinical trials) inexperienced physician and outlines the characterization of a clinical trial, the range and division of responsibilities and the performance of clinical trials according to the German Medicinal Products Act.

The "Healthy Habits, Healthy Girls" randomized controlled trial for girls: study design, protocol, and baseline results.

PubMed

Leme, Ana Carolina Barco; Philippi, Sonia Tucunduva

2015-07-01

The purpose of this article is to describe the study design, protocol, and baseline results of the "Healthy Habits, Healthy Girls" program. The intervention is being evaluated through a randomized controlled trial in 10 public schools in the city of São Paulo, Brazil. Data on the following variables were collected and assessed at baseline and will be reevaluated at 7 and 12 months: body mass index, waist circumference, dietary intake, nutrition, physical activity, social cognitive mediators, physical activity level, sedentary behaviors, self-rated physical status, and overall self-esteem. According to the baseline results, 32.4% and 23.4% of girls were overweight in the intervention and control groups, respectively, and in both groups a higher percentage failed to meet daily recommendations for moderate and vigorous physical activity and maximum screen time (TV, computer, mobile devices). There were no significant differences between the groups for most of the variables, except age (p = 0.000) and waist circumference (p = 0.014). The study showed a gap in the Brazilian literature on protocols for randomized controlled trials to prevent obesity among youth. The current study may thus be an important initial contribution to the field.

Paired Phase II Studies of Erlotinib/Bevacizumab for Advanced Bronchioloalveolar Carcinoma or Never Smokers With Advanced Non-Small-cell Lung Cancer: SWOG S0635 and S0636 Trials.

PubMed

West, Howard L; Moon, James; Wozniak, Antoinette J; Mack, Philip; Hirsch, Fred R; Bury, Martin J; Kwong, Myron; Nguyen, Dorothy D; Moore, Dennis F; Miao, Jieling; Redman, Mary; Kelly, Karen; Gandara, David R

2018-01-01

Before mutation testing of the epidermal growth factor receptor (EGFR) gene was recognized as highly associated with the activity of EGFR tyrosine kinase inhibitors (TKIs), clinically defined patient populations with bronchioloalveolar carcinoma (BAC) and never smokers were identified as likely to benefit from EGFR TKIs. From preclinical and clinical data suggesting potentially improved efficacy with a combination of an EGFR TKI and the antiangiogenic agent bevacizumab, the Southwestern Oncology Group (SWOG) initiated paired phase II trials to evaluate the combination of erlotinib/bevacizumab in patients with advanced BAC (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636). Eligible patients with BAC or adenocarcinoma with BAC features (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636) received erlotinib 150 mg/day with bevacizumab 15 mg/kg until progression or prohibitive toxicity. Never smokers with BAC were preferentially enrolled to SWOG S0636. The primary endpoint for both trials was overall survival. A total of 84 patients were enrolled in the SWOG S0635 trial and 85 in the SWOG S0636 trial. The objective response rate was 22% (3% complete response) in the SWOG S0635 trial and 50% (38% confirmed; 3% complete response) in the SWOG S0636 trial. The median progression-free survival was 5 and 7.4 months in the S0635 and S0636 trials, respectively. The median overall survival was 21 and 29.8 months, respectively. Toxicity consisted mainly of rash and diarrhea in both trials. Although the field has moved toward molecular, rather than clinical, selection of patients as optimal candidates for EGFR TKI therapy, these results support the hypothesis that a subset of patients in whom erlotinib is particularly active could receive an incremental benefit from the addition of bevacizumab. Copyright © 2017 Elsevier Inc. All rights reserved.

Differentially Variable Component Analysis (dVCA): Identifying Multiple Evoked Components using Trial-to-Trial Variability

NASA Technical Reports Server (NTRS)

Knuth, Kevin H.; Shah, Ankoor S.; Truccolo, Wilson; Ding, Ming-Zhou; Bressler, Steven L.; Schroeder, Charles E.

2003-01-01

Electric potentials and magnetic fields generated by ensembles of synchronously active neurons in response to external stimuli provide information essential to understanding the processes underlying cognitive and sensorimotor activity. Interpreting recordings of these potentials and fields is difficult as each detector records signals simultaneously generated by various regions throughout the brain. We introduce the differentially Variable Component Analysis (dVCA) algorithm, which relies on trial-to-trial variability in response amplitude and latency to identify multiple components. Using simulations we evaluate the importance of response variability to component identification, the robustness of dVCA to noise, and its ability to characterize single-trial data. Finally, we evaluate the technique using visually evoked field potentials recorded at incremental depths across the layers of cortical area VI, in an awake, behaving macaque monkey.

Recurrent urinary tract infections and complications after symptomatic versus antibiotic treatment: follow-up of a randomised controlled trial.

PubMed

Bleidorn, Jutta; Hummers-Pradier, Eva; Schmiemann, Guido; Wiese, Birgitt; Gágyor, Ildikó

2016-01-01

Uncomplicated urinary tract infections (UTI) are common in general practice, and are usually treated with antibiotics. Recurrent UTI often pose a serious problem for affected women. Little is known about recurrent UTI and complications when uncomplicated UTI are treated without antibiotics. With ICUTI (Immediate vs. conditional antibiotic use in uncomplicated UTI, funded by BMBF No. 01KG1105) we assessed whether initial symptomatic treatment with ibuprofen could be a treatment alternative for uncomplicated UTI. The presented analysis aims to assess the influence of initial (non-)antibiotic treatment on recurrent UTI rates and pyelonephritis after day 28 up to 6 months after trial participation. This study is a retrospective long-term follow-up analysis of ICUTI patients, surveyed telephonically six months after inclusion in the trial. Recurrent UTI, pyelonephritis or hospitalizations were documented. Statistical evaluation was performed by descriptive and multivariate analyses with SPSS 21. For the six months follow-up survey, 386 trial participants could be contacted (494 had been included in ICUTI initially, 446 had completed the trial). From day 28 until 6 months after inclusion in ICUTI, 84 recurrent UTI were reported by 80 patients. Univariate and multivariate analyses showed no effect of initial treatment group or antibiotic treatment on number of patients with recurrent UTI. Yet, both analyses showed that patients with a history of previous UTI had significantly more often recurrent UTI. Pyelonephritis occurred in two patients of the antibiotic group and in one patient in the non-antibiotic group. This follow-up analysis of a trial comparing antibiotic vs. symptomatic treatment for uncomplicated UTI showed that non-antibiotic treatment has no negative impact on recurrent UTI rates or pyelonephritis after day 28 and up to six months after initial treatment. Thus, a four week follow-up in UTI trials seems adequate.

Children's Oncology Group's 2013 blueprint for research: behavioral science.

PubMed

Noll, Robert B; Patel, Sunita K; Embry, Leanne; Hardy, Kristina K; Pelletier, Wendy; Annett, Robert D; Patenaude, Andrea; Lown, E Anne; Sands, Stephen A; Barakat, Lamia P

2013-06-01

Behavioral science has long played a central role in pediatric oncology clinical service and research. Early work focused on symptom relief related to side effects of chemotherapy and pain management related to invasive medical procedures. As survival rates improved, the focused has shifted to examination of the psychosocial impact, during and after treatment, of pediatric cancer and its treatment on children and their families. The success of the clinical trials networks related to survivorship highlights an even more critical role in numerous domains of psychosocial research and care. Within the cooperative group setting, the field of behavioral science includes psychologists, social workers, physicians, nurses, and parent advisors. The research agenda of this group of experts needs to focus on utilization of psychometrically robust measures to evaluate the impact of treatment on children with cancer and their families during and after treatment ends. Over the next 5 years, the field of behavioral science will need to develop and implement initiatives to expand use of standardized neurocognitive and behavior batteries; increase assessment of neurocognition using technology; early identification of at-risk children/families; establish standards for evidence-based psychosocial care; and leverage linkages with the broader behavioral health pediatric oncology community to translate empirically supported research clinical trials care to practice. Copyright © 2012 Wiley Periodicals, Inc.

Dicotyledon Weed Quantification Algorithm for Selective Herbicide Application in Maize Crops.

PubMed

Laursen, Morten Stigaard; Jørgensen, Rasmus Nyholm; Midtiby, Henrik Skov; Jensen, Kjeld; Christiansen, Martin Peter; Giselsson, Thomas Mosgaard; Mortensen, Anders Krogh; Jensen, Peter Kryger

2016-11-04

The stricter legislation within the European Union for the regulation of herbicides that are prone to leaching causes a greater economic burden on the agricultural industry through taxation. Owing to the increased economic burden, research in reducing herbicide usage has been prompted. High-resolution images from digital cameras support the studying of plant characteristics. These images can also be utilized to analyze shape and texture characteristics for weed identification. Instead of detecting weed patches, weed density can be estimated at a sub-patch level, through which even the identification of a single plant is possible. The aim of this study is to adapt the monocot and dicot coverage ratio vision (MoDiCoVi) algorithm to estimate dicotyledon leaf cover, perform grid spraying in real time, and present initial results in terms of potential herbicide savings in maize. The authors designed and executed an automated, large-scale field trial supported by the Armadillo autonomous tool carrier robot. The field trial consisted of 299 maize plots. Half of the plots (parcels) were planned with additional seeded weeds; the other half were planned with naturally occurring weeds. The in-situ evaluation showed that, compared to conventional broadcast spraying, the proposed method can reduce herbicide usage by 65% without measurable loss in biological effect.

Dicotyledon Weed Quantification Algorithm for Selective Herbicide Application in Maize Crops

PubMed Central

Laursen, Morten Stigaard; Jørgensen, Rasmus Nyholm; Midtiby, Henrik Skov; Jensen, Kjeld; Christiansen, Martin Peter; Giselsson, Thomas Mosgaard; Mortensen, Anders Krogh; Jensen, Peter Kryger

2016-01-01

The stricter legislation within the European Union for the regulation of herbicides that are prone to leaching causes a greater economic burden on the agricultural industry through taxation. Owing to the increased economic burden, research in reducing herbicide usage has been prompted. High-resolution images from digital cameras support the studying of plant characteristics. These images can also be utilized to analyze shape and texture characteristics for weed identification. Instead of detecting weed patches, weed density can be estimated at a sub-patch level, through which even the identification of a single plant is possible. The aim of this study is to adapt the monocot and dicot coverage ratio vision (MoDiCoVi) algorithm to estimate dicotyledon leaf cover, perform grid spraying in real time, and present initial results in terms of potential herbicide savings in maize. The authors designed and executed an automated, large-scale field trial supported by the Armadillo autonomous tool carrier robot. The field trial consisted of 299 maize plots. Half of the plots (parcels) were planned with additional seeded weeds; the other half were planned with naturally occurring weeds. The in-situ evaluation showed that, compared to conventional broadcast spraying, the proposed method can reduce herbicide usage by 65% without measurable loss in biological effect. PMID:27827908

Feasibility and acceptability of the DSM-5 Field Trial procedures in the Johns Hopkins Community Psychiatry Programs.

PubMed

Clarke, Diana E; Wilcox, Holly C; Miller, Leslie; Cullen, Bernadette; Gerring, Joan; Greiner, Lisa H; Newcomer, Alison; McKitty, Mellisha V; Regier, Darrel A; Narrow, William E

2014-06-01

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) contains criteria for psychiatric diagnoses that reflect advances in the science and conceptualization of mental disorders and address the needs of clinicians. DSM-5 also recommends research on dimensional measures of cross-cutting symptoms and diagnostic severity, which are expected to better capture patients' experiences with mental disorders. Prior to its May 2013 release, the American Psychiatric Association (APA) conducted field trials to examine the feasibility, clinical utility, reliability, and where possible, the validity of proposed DSM-5 diagnostic criteria and dimensional measures. The methods and measures proposed for the DSM-5 field trials were pilot tested in adult and child/adolescent clinical samples, with the goal to identify and correct design and procedural problems with the proposed methods before resources were expended for the larger DSM-5 Field Trials. Results allowed for the refinement of the protocols, procedures, and measures, which facilitated recruitment, implementation, and completion of the DSM-5 Field Trials. These results highlight the benefits of pilot studies in planning large multisite studies. Copyright © 2013, American Psychiatric Association. All rights reserved.

Rapid Onset of Retinal Toxicity From High-Dose Hydroxychloroquine Given for Cancer Therapy.

PubMed

Leung, Loh-Shan B; Neal, Joel W; Wakelee, Heather A; Sequist, Lecia V; Marmor, Michael F

2015-10-01

To report rapid onset of retinal toxicity in a series of patients followed on high-dose (1000 mg daily) hydroxychloroquine during an oncologic clinical trial studying hydroxychloroquine with erlotinib for non-small cell lung cancer. Retrospective observational case series. Ophthalmic surveillance was performed on patients in a multicenter clinical trial testing high-dose (1000 mg daily) hydroxychloroquine for advanced non-small cell lung cancer. The US Food & Drug Administration-recommended screening protocol included only visual acuity testing, dilated fundus examination, Amsler grid testing, and color vision testing. In patients seen at Stanford, additional sensitive screening procedures were added at the discretion of the retinal physician: high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, Humphrey visual field (HVF) testing, and multifocal electroretinography (mfERG). Out of the 7 patients having exposure of at least 6 months, 2 developed retinal toxicity (at 11 and 17 months of exposure). Damage was identified by OCT imaging, mfERG testing, and, in 1 case, visual field testing. Fundus autofluorescence imaging remained normal. Neither patient had symptomatic visual acuity loss. These cases show that high doses of hydroxychloroquine can initiate the development of retinal toxicity within 1-2 years. Although synergy with erlotinib is theoretically possible, there are no prior reports of erlotinib-associated retinal toxicity despite over a decade of use in oncology. These results also suggest that sensitive retinal screening tests should be added to ongoing and future clinical trials involving high-dose hydroxychloroquine to improve safety monitoring and preservation of vision. Published by Elsevier Inc.

Effect of Risk of Bias on the Effect Size of Meta-Analytic Estimates in Randomized Controlled Trials in Periodontology and Implant Dentistry.

PubMed

Faggion, Clovis Mariano; Wu, Yun-Chun; Scheidgen, Moritz; Tu, Yu-Kang

2015-01-01

Risk of bias (ROB) may threaten the internal validity of a clinical trial by distorting the magnitude of treatment effect estimates, although some conflicting information on this assumption exists. The objective of this study was evaluate the effect of ROB on the magnitude of treatment effect estimates in randomized controlled trials (RCTs) in periodontology and implant dentistry. A search for Cochrane systematic reviews (SRs), including meta-analyses of RCTs published in periodontology and implant dentistry fields, was performed in the Cochrane Library in September 2014. Random-effect meta-analyses were performed by grouping RCTs with different levels of ROBs in three domains (sequence generation, allocation concealment, and blinding of outcome assessment). To increase power and precision, only SRs with meta-analyses including at least 10 RCTs were included. Meta-regression was performed to investigate the association between ROB characteristics and the magnitudes of intervention effects in the meta-analyses. Of the 24 initially screened SRs, 21 SRs were excluded because they did not include at least 10 RCTs in the meta-analyses. Three SRs (two from periodontology field) generated information for conducting 27 meta-analyses. Meta-regression did not reveal significant differences in the relationship of the ROB level with the size of treatment effect estimates, although a trend for inflated estimates was observed in domains with unclear ROBs. In this sample of RCTs, high and (mainly) unclear risks of selection and detection biases did not seem to influence the size of treatment effect estimates, although several confounders might have influenced the strength of the association.

A cross-sectional analysis of HIV and hepatitis C clinical trials 2007 to 2010: the relationship between industry sponsorship and randomized study design.

PubMed

Goswami, Neela D; Tsalik, Ephraim L; Naggie, Susanna; Miller, William C; Horton, John R; Pfeiffer, Christopher D; Hicks, Charles B

2014-01-22

The proportion of clinical research sponsored by industry will likely continue to expand as federal funds for academic research decreases, particularly in the fields of HIV/AIDS and hepatitis C (HCV). While HIV and HCV continue to burden the US population, insufficient data exists as to how industry sponsorship affects clinical trials involving these infectious diseases. Debate exists about whether pharmaceutical companies undertake more market-driven research practices to promote therapeutics, or instead conduct more rigorous trials than their non-industry counterparts because of increased resources and scrutiny. The ClinicalTrials.gov registry, which allows investigators to fulfill a federal mandate for public trial registration, provides an opportunity for critical evaluation of study designs for industry-sponsored trials, independent of publication status. As part of a large public policy effort, the Clinical Trials Transformation Initiative (CTTI) recently transformed the ClinicalTrials.gov registry into a searchable dataset to facilitate research on clinical trials themselves. We conducted a cross-sectional analysis of 477 HIV and HCV drug treatment trials, registered with ClinicalTrials.gov from 1 October 2007 to 27 September 2010, to study the relationship of study sponsorship with randomized study design. The likelihood of using randomization given industry (versus non-industry) sponsorship was reported with prevalence ratios (PR). PRs were estimated using crude and stratified tabular analysis and Poisson regression adjusting for presence of a data monitoring committee, enrollment size, study phase, number of study sites, inclusion of foreign study sites, exclusion of persons older than age 65, and disease condition. The crude PR was 1.17 (95% CI 0.94, 1.45). Adjusted Poisson models produced a PR of 1.13 (95% CI 0.82, 1.56). There was a trend toward mild effect measure modification by study phase, but this was not statistically significant. In stratified tabular analysis the adjusted PR was 1.14 (95% CI 0.78, 1.68) among phase 2/3 trials and 1.06 (95% CI 0.50, 2.22) among phase 4 trials. No significant relationship was found between industry sponsorship and use of randomization in trial design in this cross-sectional study. Prospective studies evaluating other aspects of trial design may shed further light on the relationship between industry sponsorship and appropriate trial methodology.

A cross-sectional analysis of HIV and hepatitis C clinical trials 2007 to 2010: the relationship between industry sponsorship and randomized study design

PubMed Central

2014-01-01

Background The proportion of clinical research sponsored by industry will likely continue to expand as federal funds for academic research decreases, particularly in the fields of HIV/AIDS and hepatitis C (HCV). While HIV and HCV continue to burden the US population, insufficient data exists as to how industry sponsorship affects clinical trials involving these infectious diseases. Debate exists about whether pharmaceutical companies undertake more market-driven research practices to promote therapeutics, or instead conduct more rigorous trials than their non-industry counterparts because of increased resources and scrutiny. The ClinicalTrials.gov registry, which allows investigators to fulfill a federal mandate for public trial registration, provides an opportunity for critical evaluation of study designs for industry-sponsored trials, independent of publication status. As part of a large public policy effort, the Clinical Trials Transformation Initiative (CTTI) recently transformed the ClinicalTrials.gov registry into a searchable dataset to facilitate research on clinical trials themselves. Methods We conducted a cross-sectional analysis of 477 HIV and HCV drug treatment trials, registered with ClinicalTrials.gov from 1 October 2007 to 27 September 2010, to study the relationship of study sponsorship with randomized study design. The likelihood of using randomization given industry (versus non-industry) sponsorship was reported with prevalence ratios (PR). PRs were estimated using crude and stratified tabular analysis and Poisson regression adjusting for presence of a data monitoring committee, enrollment size, study phase, number of study sites, inclusion of foreign study sites, exclusion of persons older than age 65, and disease condition. Results The crude PR was 1.17 (95% CI 0.94, 1.45). Adjusted Poisson models produced a PR of 1.13 (95% CI 0.82, 1.56). There was a trend toward mild effect measure modification by study phase, but this was not statistically significant. In stratified tabular analysis the adjusted PR was 1.14 (95% CI 0.78, 1.68) among phase 2/3 trials and 1.06 (95% CI 0.50, 2.22) among phase 4 trials. Conclusions No significant relationship was found between industry sponsorship and use of randomization in trial design in this cross-sectional study. Prospective studies evaluating other aspects of trial design may shed further light on the relationship between industry sponsorship and appropriate trial methodology. PMID:24450313

Field trials of line transect methods applied to estimation of desert tortoise abundance

USGS Publications Warehouse

Anderson, David R.; Burnham, Kenneth P.; Lubow, Bruce C.; Thomas, L. E. N.; Corn, Paul Stephen; Medica, Philip A.; Marlow, R.W.

2001-01-01

We examine the degree to which field observers can meet the assumptions underlying line transect sampling to monitor populations of desert tortoises (Gopherus agassizii). We present the results of 2 field trials using artificial tortoise models in 3 size classes. The trials were conducted on 2 occasions on an area south of Las Vegas, Nevada, where the density of the test population was known. In the first trials, conducted largely by experienced biologists who had been involved in tortoise surveys for many years, the density of adult tortoise models was well estimated (-3.9% bias), while the bias was higher (-20%) for subadult tortoise models. The bias for combined data was -12.0%. The bias was largely attributed to the failure to detect all tortoise models on or near the transect centerline. The second trials were conducted with a group of largely inexperienced student volunteers and used somewhat different searching methods, and the results were similar to the first trials. Estimated combined density of subadult and adult tortoise models had a negative bias (-7.3%), again attributable to failure to detect some models on or near the centerline. Experience in desert tortoise biology, either comparing the first and second trials or in the second trial with 2 experienced biologists versus 16 novices, did not have an apparent effect on the quality of the data or the accuracy of the estimates. Observer training, specific to line transect sampling, and field testing are important components of a reliable survey. Line transect sampling represents a viable method for large-scale monitoring of populations of desert tortoise; however, field protocol must be improved to assure the key assumptions are met.

The Breast International Group 1-98 trial: big results for women with hormone-sensitive early breast cancer.

PubMed

Monnier, Alain M

2007-05-01

As there is a risk for relapse in early breast cancer, especially at 1-3 years post surgery, the need for adjuvant therapy is clear. In terms of disease-free survival, aromatase inhibitors have emerged as superior to tamoxifen for the adjuvant treatment of hormone-sensitive breast cancer in several Phase III clinical trials. Of these trials, the Breast International Group (BIG) 1-98 trial stands out as unique in design, as it is the only trial to address whether an aromatase inhibitor is more effective as initial adjuvant therapy or as sequential therapy with an aromatase inhibitor and tamoxifen in either order and in rigor of end points and safety evaluations. When compared with tamoxifen, letrozole has been shown to significantly reduce recurrence risk in the overall population by 19% and also significantly reduced recurrence risk in the patient subgroups at increased risk: node-positive and previously chemotherapy-treated patients. Letrozole is the only aromatase inhibitor to demonstrate a significant 27% reduction in the risk of distant metastases (p = 0.001) in the clinically relevant, hormone receptor-positive population in the initial adjuvant setting. Recent results also suggest that letrozole in particular reduces the risk of distant metastases early on after initial surgery for breast cancer. This is important, as early distant metastatic events compose the majority of early recurrences and are a well-recognized predictor of breast cancer death. Letrozole has been found to be well tolerated in the initial adjuvant treatment setting, and these data have been confirmed by long-term safety data from the monotherapy analysis in the BIG 1-98 study. Thus far, the results from the BIG 1-98 trial provide clear support for the use of letrozole in the initial adjuvant treatment of breast cancer. Future studies will provide the definitive answer to questions of which initial adjuvant therapy is superior (i.e., anastrozole or letrozole) and information as to the optimal treatment strategy (i.e., initial adjuvant aromatase inhibitor therapy or sequential adjuvant aromatase inhibitor therapy).

Nitrogen Isotopes as an Indicator of Long-Term N Cycling in a Grazed Temperate Pasture Receiving Different Rates of Superphosphate Fertilizer and Irrigation for ~50 Years

NASA Astrophysics Data System (ADS)

Mudge, P. L.; Schipper, L. A.; Ghani, A.; Baisden, W. T.; Dodd, M.

2010-12-01

Pastoral agriculture is the dominant land use in New Zealand and intensification (as a result of fertilizer inputs and in some areas irrigation) has led to increased nitrogen (N) losses to the wider environment. An indicator that could identify soils which are vulnerable to N loss would be useful for the development of management practices and regulations aimed at reducing unwanted N losses. The natural abundance of 15N relative to 14N (δ15N) in soils is one potential indicator. Most N cycle processes associated with N losses (e.g. nitrification, denitrification, and volatilisation) discriminate against 15N and therefore soil δ15N could provide an indication of cumulative N losses. In this study we measured δ15N in archived soils from two long-term field trials receiving different rates of superphosphate fertilizer and irrigation. Both trials were in mid-Canterbury, New Zealand and were grazed by sheep. The fertilizer trial began in 1952, and treatments used were the control (nilP), 376 kg superphosphate ha-1 y-1 (376PA) and a treatment where 376 kg superphosphate ha-1 y-1 was applied between 1952 and 1957, no fertilizer from 1958 to 1979 and then 250 kg superphosphate ha-1 y-1 from 1980 to 2009 (376-0-250PA). The irrigation trial was initiated in 1949 and ceased in 2002. The dryland treatment and treatments irrigated when soil moisture was 10% and 20% were used in this study. From 1958, soil samples (0-75 mm depth) were taken annually from each trial, air dried and archived. Soil samples at four year intervals were analysed for this study. Pasture production varied considerably between treatments, with higher rates of fertilizer and irrigation promoting greater pasture growth and therefore higher grazing intensities. Initially δ15N was about the same (3.3‰) in all treatments of both trials. δ15N in the 376PA treatment of the fertilizer trial increased gradually with time and by 2009 was 4.5‰. In the 376-0-250PA treatment, δ15N stayed constant until about 1980 and then increased rapidly, which coincided with re-commencement of P fertilizer application. δ15N in the nilP treatment initially declined slightly and then remained relatively constant. In the irrigation trial, δ15N stayed constant (~3.3‰) in all three treatments up until around 1985 and then increased. After 1985 there was a separation between treatments with δ15N in the 20% treatment increasing marginally more than the 10% treatment and considerably more than the dryland treatment. We had anticipated an increase and divergence in δ15N values from the start of the irrigation trial. In general soil δ15N scaled with intensity of grazing, which suggests that N losses were greater under more intensive systems. δ15N therefore shows potential as an indicator of the vulnerability of soils to N loss. Further work will investigate the relationship between changes in δ15N and total C and N at these two trials, and future work will seek to directly relate soil δ15N to cumulative N losses via leaching and gaseous emissions.

Predictors of Adherence in the Women’s Health Initiative Calcium and Vitamin D Trial

PubMed Central

Brunner, R.; Dunbar-Jacob, J.; LeBoff, M. S.; Granek, I.; Bowen, D.; Snetselaar, L. G.; Shumaker, S. A.; Ockene, J.; Rosal, M.; Wactawski-Wende, J.; Cauley, J.; Cochrane, B.; Tinker, L.; Jackson, R.; Wang, C. Y.; Wu, L.

2010-01-01

The authors analyzed data from the Women’s Health Initiative (WHI) Calcium and Vitamin D Supplementation Trial (CaD) to learn more about factors affecting adherence to clinical trial study pills (both active and placebo). Most participants (36,282 postmenopausal women aged 50–79 years) enrolled in CaD 1 year after joining either a hormone trial or the dietary modification trial of WHI. The WHI researchers measured adherence to study pills by weighing the amount of remaining pills at an annual study visit; adherence was primarily defined as taking ≥ 80% of the pills. The authors in this study examined a number of behavioral, demographic, procedural, and treatment variables for association with study pill adherence. They found that relatively simple procedures (ie, phone contact early in the study [4 weeks post randomization] and direct social contact) later in the trial may improve adherence. Also, at baseline, past pill-use experiences, personal supplement use, and relevant symptoms may be predictive of adherence in a supplement trial. PMID:19064373

2017 Cardiovascular and Stroke Endpoint Definitions for Clinical Trials.

PubMed

Hicks, Karen A; Mahaffey, Kenneth W; Mehran, Roxana; Nissen, Steven E; Wiviott, Stephen D; Dunn, Billy; Solomon, Scott D; Marler, John R; Teerlink, John R; Farb, Andrew; Morrow, David A; Targum, Shari L; Sila, Cathy A; Thanh Hai, Mary T; Jaff, Michael R; Joffe, Hylton V; Cutlip, Donald E; Desai, Akshay S; Lewis, Eldrin F; Gibson, C Michael; Landray, Martin J; Lincoff, A Michael; White, Christopher J; Brooks, Steven S; Rosenfield, Kenneth; Domanski, Michael J; Lansky, Alexandra J; McMurray, John J V; Tcheng, James E; Steinhubl, Steven R; Burton, Paul; Mauri, Laura; O'Connor, Christopher M; Pfeffer, Marc A; Hung, H M James; Stockbridge, Norman L; Chaitman, Bernard R; Temple, Robert J

2018-03-06

This publication describes uniform definitions for cardiovascular and stroke outcomes developed by the Standardized Data Collection for Cardiovascular Trials Initiative and the U.S. Food and Drug Administration (FDA). The FDA established the Standardized Data Collection for Cardiovascular Trials Initiative in 2009 to simplify the design and conduct of clinical trials intended to support marketing applications. The writing committee recognizes that these definitions may be used in other types of clinical trials and clinical care processes where appropriate. Use of these definitions at the FDA has enhanced the ability to aggregate data within and across medical product development programs, conduct meta-analyses to evaluate cardiovascular safety, integrate data from multiple trials, and compare effectiveness of drugs and devices. Further study is needed to determine whether prospective data collection using these common definitions improves the design, conduct, and interpretability of the results of clinical trials. Copyright © 2018 American College of Cardiology Foundation and American Heart Association, Inc. Published by Elsevier Inc. All rights reserved.

Restoring the biological crust cover of soils across biomes in arid North America

NASA Astrophysics Data System (ADS)

Garcia-Pichel, Ferran; Antoninka, Anita; Bowker, Matthew; Giraldo Silva, Ana; Nelson, Corey; Velasco Ayuso, Sergio; Barger, Nichole; Belnap, Jayne; Reed, Sasha; Duniway, Michael

2015-04-01

Biological soil crust communities provide important ecosystem services to arid lands, particularly regarding soil fertility and stability against erosion. In North America, and in many other areas of the globe, increasingly intense human activities, ranging from cattle grazing to military training, have resulted in the significant deterioration of biological soil surface cover of soils. With the intent of attaining sustainable land use practices, we are conducting a 5-year, multi-institutional research effort to develop feasible soil crusts restoration strategies for US military lands. We are including field sites of varying climatic regions (warm and cold deserts, in the Chihuahuan Desert and in the Great Basin, respectively) and varying edaphic characteristics (sandy and silty soils in each). We have multiple aims. First, we aim to establishing effective "biocrust nurseries" that produce viable and pedigreed inoculum, as a supply center for biocrust restoration and for research and development. Second, we aim to develop optimal field application methods of biocrust inoculum in a series of field trials. Currently in our second year of research, we will be reporting on significant advances made on optimizing methodologies for the large-scale supply of inoculum based on a) pedigreed laboratory cultures that match the microbial community structure of the original sites, and b) "in soil" biomass enhancement, whereby small amounts of local crusts are nursed under greenhouse conditions to yield hundred-fold increases in biomass without altering significantly community structure. We will also report on field trials for methodologies in field application, which included shading, watering, application of chemical polymers, and soil surface roughening. In a soon-to-be-initiated effort we also aim to evaluate soil and plant responses to biocrust restoration with respect to plant community structure, soil fertility, and soil stability, in multi-factorial field experiments. An important part of the plan will be to construct effective channels for sharing challenges and solutions in biocrust restoration with military and federal land managers.

Dark-Adapted Chromatic Perimetry for Measuring Rod Visual Fields in Patients with Retinitis Pigmentosa

PubMed Central

Bennett, Lea D.; Klein, Martin; Locke, Kirsten G.; Kiser, Kelly; Birch, David G.

2017-01-01

Purpose Although rod photoreceptors are initially affected in retinitis pigmentosa (RP), the full-field of rod vision is not routinely characterized due to the unavailability of commercial devices detecting rod sensitivity. The purpose of this study was to quantify rod-mediated vision in the peripheral field from patients with RP using a new commercially available perimeter. Methods Participants had one eye dilated and dark-adapted for 45 minutes. A dark-adapted chromatic (DAC) perimeter tested 80 loci 144° horizontally and 72° vertically with cyan stimuli. The number of rod-mediated loci (RML) were analyzed based on normal cone sensitivity (method 1) and associated with full-field electroretinography (ERG) responses by Pearson's r correlation and linear regression. In a second cohort of patients with RP, RML were identified by two-color perimetry (cyan and red; method 2). The two methods for ascribing rod function were compared by Bland-Altman analysis. Results Method 1 RML were correlated with responses to the 0.01 cd.s/m2 flash (P < 0.001), while total sensitivity to the cyan stimulus showed correlation with responses to the 3.0 cd.s/m2 flash (P < 0.0001). Method 2 detected a mean of 10 additional RML compared to method 1. Conclusions Scotopic fields measured with the DAC detected rod sensitivity across the full visual field, even in some patients who had nondetectable rod ERGs. Two-color perimetry is warranted when sensitivity to the cyan stimulus is reduced to ≤20 dB to get a true estimation of rod function. Translational Relevance Many genetic forms of retinitis pigmentosa (RP) are caused by mutations in rod-specific genes. However, treatment trials for patients with RP have relied primarily on photopic (cone-mediated) tests as outcome measures because there are a limited number of available testing methods designed to evaluate rod function. Thus, efficient methods for quantifying rod-mediated vision are needed for the rapidly increasing numbers of clinical trials. PMID:28798898

Soil stabilization field trial : interim report II.

DOT National Transportation Integrated Search

2002-02-01

Shrinkage cracks in cement-stabilized bases/subbase can be alleviated by specifying the right cement dosage, or by other additives/procedures that suppress crack susceptibility. A field trial of six 1000 ft sections to investigate several alternative...

Soil stabilization field trial : interim report.

DOT National Transportation Integrated Search

2001-04-01

Shrinkage cracks in cement-stabilized bases/subbase can be alleviated by specifying : the right cement dosage, or by other additives/procedures that suppress crack susceptibility. A field : trial of six 1000 ft test sections to investigate several al...

Field trial of solvent-free emulsion in Oregon : appendices.

DOT National Transportation Integrated Search

2003-03-01

This final report summarizes construction, laboratory and performance information gathered by ODOT personnel from a single field trial of solvent-free emulsion mix constructed in June 2001. The solvent-free emulsion mix presented several placement pr...

Soil stabilization field trial : interim report I.

DOT National Transportation Integrated Search

2001-04-01

Shrinkage cracks in cement-stabilized bases/subbase can be alleviated by specifying the right cement dosage, or by other additives/procedures that suppress crack susceptibility. A field trial of six 1000 ft test sections to investigate several altern...

Soil stabilization field trial : interim report III.

DOT National Transportation Integrated Search

2003-11-01

Shrinkage cracks in cement-stabilized bases/subbase can be alleviated by specifying the right cement dosage, or by other additives/procedures that suppress crack susceptibility. A field trial of six 1000 ft test sections to investigate several altern...

The child and adolescent psychiatry trials network (CAPTN): infrastructure development and lessons learned

PubMed Central

Shapiro, Mark; Silva, Susan G; Compton, Scott; Chrisman, Allan; DeVeaugh-Geiss, Joseph; Breland-Noble, Alfiee; Kondo, Douglas; Kirchner, Jerry; March, John S

2009-01-01

Background In 2003, the National Institute of Mental Health funded the Child and Adolescent Psychiatry Trials Network (CAPTN) under the Advanced Center for Services and Intervention Research (ACSIR) mechanism. At the time, CAPTN was believed to be both a highly innovative undertaking and a highly speculative one. One reviewer even suggested that CAPTN was "unlikely to succeed, but would be a valuable learning experience for the field." Objective To describe valuable lessons learned in building a clinical research network in pediatric psychiatry, including innovations intended to decrease barriers to research participation. Methods The CAPTN Team has completed construction of the CAPTN network infrastructure, conducted a large, multi-center psychometric study of a novel adverse event reporting tool, and initiated a large antidepressant safety registry and linked pharmacogenomic study focused on severe adverse events. Specific challenges overcome included establishing structures for network organization and governance; recruiting over 150 active CAPTN participants and 15 child psychiatry training programs; developing and implementing procedures for site contracts, regulatory compliance, indemnification and malpractice coverage, human subjects protection training and IRB approval; and constructing an innovative electronic casa report form (eCRF) running on a web-based electronic data capture system; and, finally, establishing procedures for audit trail oversight requirements put forward by, among others, the Food and Drug Administration (FDA). Conclusion Given stable funding for network construction and maintenance, our experience demonstrates that judicious use of web-based technologies for profiling investigators, investigator training, and capturing clinical trials data, when coupled to innovative approaches to network governance, data management and site management, can reduce the costs and burden and improve the feasibility of incorporating clinical research into routine clinical practice. Having successfully achieved its initial aim of constructing a network infrastructure, CAPTN is now a capable platform for large safety registries, pharmacogenetic studies, and randomized practical clinical trials in pediatric psychiatry. PMID:19320979

Correlation functions from a unified variational principle: Trial Lie groups

NASA Astrophysics Data System (ADS)

Balian, R.; Vénéroni, M.

2015-11-01

Time-dependent expectation values and correlation functions for many-body quantum systems are evaluated by means of a unified variational principle. It optimizes a generating functional depending on sources associated with the observables of interest. It is built by imposing through Lagrange multipliers constraints that account for the initial state (at equilibrium or off equilibrium) and for the backward Heisenberg evolution of the observables. The trial objects are respectively akin to a density operator and to an operator involving the observables of interest and the sources. We work out here the case where trial spaces constitute Lie groups. This choice reduces the original degrees of freedom to those of the underlying Lie algebra, consisting of simple observables; the resulting objects are labeled by the indices of a basis of this algebra. Explicit results are obtained by expanding in powers of the sources. Zeroth and first orders provide thermodynamic quantities and expectation values in the form of mean-field approximations, with dynamical equations having a classical Lie-Poisson structure. At second order, the variational expression for two-time correlation functions separates-as does its exact counterpart-the approximate dynamics of the observables from the approximate correlations in the initial state. Two building blocks are involved: (i) a commutation matrix which stems from the structure constants of the Lie algebra; and (ii) the second-derivative matrix of a free-energy function. The diagonalization of both matrices, required for practical calculations, is worked out, in a way analogous to the standard RPA. The ensuing structure of the variational formulae is the same as for a system of non-interacting bosons (or of harmonic oscillators) plus, at non-zero temperature, classical Gaussian variables. This property is explained by mapping the original Lie algebra onto a simpler Lie algebra. The results, valid for any trial Lie group, fulfill consistency properties and encompass several special cases: linear responses, static and time-dependent fluctuations, zero- and high-temperature limits, static and dynamic stability of small deviations.

Biological control of Heterodera glycines by spore-forming plant growth-promoting rhizobacteria (PGPR) on soybean.

PubMed

Xiang, Ni; Lawrence, Kathy S; Kloepper, Joseph W; Donald, Patricia A; McInroy, John A

2017-01-01

Heterodera glycines, the soybean cyst nematode, is the most economically important plant-parasitic nematode on soybean production in the U.S. The objectives of this study were to evaluate the potential of plant growth-promoting rhizobacteria (PGPR) strains for mortality of H. glycines J2 in vitro and for reducing nematode population density on soybean in greenhouse, microplot, and field trials. The major group causing mortality to H. glycines in vitro was the genus Bacillus that consisted of 92.6% of the total 663 PGPR strains evaluated. The subsequent greenhouse, microplot, and field trials indicated that B. velezensis strain Bve2 consistently reduced H. glycines cyst population density at 60 DAP. Bacillus mojavensis strain Bmo3 suppressed H. glycines cyst and total H. glycines population density under greenhouse conditions. Bacillus safensis strain Bsa27 and Mixture 1 (Bve2 + Bal13) reduced H. glycines cyst population density at 60 DAP in the field trials. Bacillus subtilis subsp. subtilis strains Bsssu2 and Bsssu3, and B. velezensis strain Bve12 increased early soybean growth including plant height and plant biomass in the greenhouse trials. Bacillus altitudinis strain Bal13 increased early plant growth on soybean in the greenhouse and microplot trials. Mixture 2 (Abamectin + Bve2 + Bal13) increased early plant growth in the microplot trials at 60 DAP, and also enhanced soybean yield at harvest in the field trials. These results demonstrated that individual PGPR strains and mixtures can reduce H. glycines population density in the greenhouse, microplot, and field conditions, and increased yield of soybean.

Sequential analysis applied to clinical trials in dentistry: a systematic review.

PubMed

Bogowicz, P; Flores-Mir, C; Major, P W; Heo, G

2008-01-01

Clinical trials employ sequential analysis for the ethical and economic benefits it brings. In dentistry, as in other fields, resources are scarce and efforts are made to ensure that patients are treated ethically. The objective of this systematic review was to characterise the use of sequential analysis for clinical trials in dentistry. We searched various databases from 1900 through to January 2008. Articles were selected for review if they were clinical trials in the field of dentistry that had applied some form of sequential analysis. Selection was carried out independently by two of the authors. We included 18 trials from various specialties, which involved many different interventions. We conclude that sequential analysis seems to be underused in this field but that there are sufficient methodological resources in place for future applications.Evidence-Based Dentistry (2008) 9, 55-62. doi:10.1038/sj.ebd.6400587.

Axicabtagene ciloleucel (KTE-C19), an anti-CD19 CAR T therapy for the treatment of relapsed/refractory aggressive B-cell non-Hodgkin's lymphoma.

PubMed

Jain, Michael D; Bachmeier, Christina A; Phuoc, Vania H; Chavez, Julio C

2018-01-01

Adoptive T-cell immunotherapy is a rapidly growing field and is shifting the paradigm of clinical cancer treatment. Axicabtagene ciloleucel (axi-cel) is an anti-CD19 chimeric antigen receptor T-cell therapy that was initially developed at the National Cancer Institute and has recently been commercially approved by the US Food and Drug Administration for relapsed or refractory aggressive non-Hodgkin's lymphomas including diffuse large B-cell lymphoma and its variants. The ZUMA-1 Phase I and II clinical trials formed the basis of the US Food and Drug Administration approval of this product, and we discuss the particulars of the clinical trials and the pharmacology of axi-cel. In addition, we review the CD19 chimeric antigen receptor T-specific toxicities of cytokine release syndrome and neurotoxicity, which remain the challenges to the safe delivery of this important therapy for aggressive B-cell lymphomas with poor prognosis.

Axicabtagene ciloleucel (KTE-C19), an anti-CD19 CAR T therapy for the treatment of relapsed/refractory aggressive B-cell non-Hodgkin’s lymphoma

PubMed Central

Jain, Michael D; Bachmeier, Christina A; Phuoc, Vania H; Chavez, Julio C

2018-01-01

Adoptive T-cell immunotherapy is a rapidly growing field and is shifting the paradigm of clinical cancer treatment. Axicabtagene ciloleucel (axi-cel) is an anti-CD19 chimeric antigen receptor T-cell therapy that was initially developed at the National Cancer Institute and has recently been commercially approved by the US Food and Drug Administration for relapsed or refractory aggressive non-Hodgkin’s lymphomas including diffuse large B-cell lymphoma and its variants. The ZUMA-1 Phase I and II clinical trials formed the basis of the US Food and Drug Administration approval of this product, and we discuss the particulars of the clinical trials and the pharmacology of axi-cel. In addition, we review the CD19 chimeric antigen receptor T-specific toxicities of cytokine release syndrome and neurotoxicity, which remain the challenges to the safe delivery of this important therapy for aggressive B-cell lymphomas with poor prognosis. PMID:29910620

76 FR 22404 - Analgesic Clinical Trials Innovation, Opportunities, and Networks (ACTION) Initiative

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-21

..., but not limited to, specific research designs and methodological features so as to inform the future... clinical trials. Many experts in analgesic drug development believe that it is the design of the clinical trials that is at fault in this situation and that better trial designs will yield more successful...

Using regional broccoli trial data to select experimental hybrids for input into advanced yield trials

USDA-ARS?s Scientific Manuscript database

A large amount of phenotypic trait data are being generated in regional trials that are implemented as part of the Specialty Crop Research Initiative (SCRI) project entitled “Establishing an Eastern Broccoli Industry”. These data are used to identify the best entries in the trials for inclusion in ...

Field trial of a pulsed limestone diversion well

USGS Publications Warehouse

Sibrell, Philip L.; Denholm, C.; Dunn, Margaret

2013-01-01

The use of limestone diversion wells to treat acid mine drainage (AMD) is well-known, but in many cases, acid neutralization is not as complete as would be desired. Reasons for this include channeling of the water through the limestone bed, and the slow reaction rate of the limestone gravel. A new approach to improve the performance of the diversion well was tested in the field at the Jennings Environmental Education Center, near Slippery Rock, PA. In this approach, a finer size distribution of limestone was used so as to allow fluidization of the limestone bed, thus eliminating channeling and increasing particle surface area for faster reaction rates. Also, water flow was regulated through the use of a dosing siphon, so that consistent fluidization of the limestone sand could be achieved. Testing began late in the summer of 2010, and continued through November of 2011. Initial system performance during the 2010 field season was good, with the production of net alkaline water, but hydraulic problems involving air release and limestone sand retention were observed. In the summer of 2011, a finer size of limestone sand was procured for use in the system. This material fluidized more readily, but acid neutralization tapered off after several days. Subsequent observations indicated that the hydraulics of the system was compromised by the formation of iron oxides in the pipe leading to the limestone bed, which affected water distribution and flow through the bed. Although results from the field trial were mixed, it is believed that without the formation of iron oxides and plugging of the pipe, better acid neutralization and treatment would have occurred. Further tests are being considered using a different hydraulic configuration for the limestone sand fluidized bed.

Self-adaptive robot training of stroke survivors for continuous tracking movements.

PubMed

Vergaro, Elena; Casadio, Maura; Squeri, Valentina; Giannoni, Psiche; Morasso, Pietro; Sanguineti, Vittorio

2010-03-15

Although robot therapy is progressively becoming an accepted method of treatment for stroke survivors, few studies have investigated how to adapt the robot/subject interaction forces in an automatic way. The paper is a feasibility study of a novel self-adaptive robot controller to be applied with continuous tracking movements. The haptic robot Braccio di Ferro is used, in relation with a tracking task. The proposed control architecture is based on three main modules: 1) a force field generator that combines a non linear attractive field and a viscous field; 2) a performance evaluation module; 3) an adaptive controller. The first module operates in a continuous time fashion; the other two modules operate in an intermittent way and are triggered at the end of the current block of trials. The controller progressively decreases the gain of the force field, within a session, but operates in a non monotonic way between sessions: it remembers the minimum gain achieved in a session and propagates it to the next one, which starts with a block whose gain is greater than the previous one. The initial assistance gains are chosen according to a minimal assistance strategy. The scheme can also be applied with closed eyes in order to enhance the role of proprioception in learning and control. The preliminary results with a small group of patients (10 chronic hemiplegic subjects) show that the scheme is robust and promotes a statistically significant improvement in performance indicators as well as a recalibration of the visual and proprioceptive channels. The results confirm that the minimally assistive, self-adaptive strategy is well tolerated by severely impaired subjects and is beneficial also for less severe patients. The experiments provide detailed information about the stability and robustness of the adaptive controller of robot assistance that could be quite relevant for the design of future large scale controlled clinical trials. Moreover, the study suggests that including continuous movement in the repertoire of training is acceptable also by rather severely impaired subjects and confirms the stabilizing effect of alternating vision/no vision trials already found in previous studies.

Field trial of solvent-free emulsion in Oregon : final report.

DOT National Transportation Integrated Search

2003-03-01

This final report summarizes construction, laboratory and performance information gathered by ODOT personnel from a single field trial of solvent-free emulsion mix constructed in June 2001. The solvent-free emulsion mix presented several placement pr...

Competition Between Fusarium pseudograminearum and Cochliobolus sativus Observed in Field and Greenhouse Studies.

PubMed

Troth, Erin E Gunnink; Johnston, Jeffrey A; Dyer, Alan T

2018-02-01

Among root pathogens, one of the most documented antagonisms is the suppression of Cochliobolus sativus by Fusarium (roseum) species. Unfortunately, previous studies involved single isolates of each pathogen and thus, provided no indication of the spectrum of responses that occur across the respective species. To investigate the variability in interactions between Cochliobolus sativus and Fusarium pseudograminearum, field and greenhouse trials were conducted that included monitoring of spring wheat plant health and monitoring of pathogen populations via quantitative real-time polymerase chain reaction. The interactions between two isolates of C. sativus and four isolates of F. pseudograminearum were explored in three geographically distinct wheat fields. To complement field trials and to limit potentially confounding environmental variables that are often associated with field studies, greenhouse trials were performed that investigated the interactions among and between three isolates of C. sativus and four isolates of F. pseudograminearum. Across field locations, C. sativus isolate Cs2344 consistently and significantly reduced Fusarium populations by an average of 20.1%. Similarly, F. pseudograminearum isolate Fp2228 consistently and significantly reduced C. sativus field populations by an average of 30.9%. No interaction was detected in the field between pathogen species with regards to disease or crop losses. Greenhouse results confirmed a powerful (>99%), broadly effective suppression of Fusarium populations by isolate Cs2344. Among greenhouse trials, additional isolate-isolate interactions were observed affecting Fusarium populations. Due to lower C. sativus population sizes in greenhouse trials, significant Fusarium suppression of C. sativus was only detected in one isolate-isolate interaction. This study is the first to demonstrate suppression of Fusarium spp. by C. sativus in field and greenhouse settings. These findings also reveal a complex competitive interaction between these two pathogen species that was previously unknown.

Essential Neuroscience in Immunology

PubMed Central

Chavan, Sangeeta S.; Tracey, Kevin J.

2017-01-01

The field of immunology is principally focused on the molecular mechanisms by which hematopoetic cells initiate and maintain innate and adaptive immunity. That cornerstone of attention has been expanded by recent discoveries that neuronal signals occupy a critical regulatory niche in immunity. The discovery is that neuronal circuits operating reflexively regulate innate and adaptive immunity. One particularly well-characterized circuit regulating innate immunity, the inflammatory reflex, is dependent upon action potentials transmitted to the reticuloendothelial system via the vagus and splenic nerves. This field has grown significantly with identification of several other reflexes regulating discrete immune functions. As reviewed here, the delineation of these mechanisms revealed a new understanding of immunity, enabled a first in class clinical trial using bioelectronic devices to inhibit cytokines and inflammation in rheumatoid arthritis patients, and provided a mosaic view of immunity as the integration of hematopoetic and neural responses to infection and injury. PMID:28416717

Essential Neuroscience in Immunology.

PubMed

Chavan, Sangeeta S; Tracey, Kevin J

2017-05-01

The field of immunology is principally focused on the molecular mechanisms by which hematopoietic cells initiate and maintain innate and adaptive immunity. That cornerstone of attention has been expanded by recent discoveries that neuronal signals occupy a critical regulatory niche in immunity. The discovery is that neuronal circuits operating reflexively regulate innate and adaptive immunity. One particularly well-characterized circuit regulating innate immunity, the inflammatory reflex, is dependent upon action potentials transmitted to the reticuloendothelial system via the vagus and splenic nerves. This field has grown significantly with the identification of several other reflexes regulating discrete immune functions. As outlined in this review, the delineation of these mechanisms revealed a new understanding of immunity, enabled a first-in-class clinical trial using bioelectronic devices to inhibit cytokines and inflammation in rheumatoid arthritis patients, and provided a mosaic view of immunity as the integration of hematopoietic and neural responses to infection and injury. Copyright © 2017 by The American Association of Immunologists, Inc.

Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy

PubMed Central

Hotchkiss, Richard S.; Monneret, Guillaume; Payen, Didier

2014-01-01

Sepsis — severe life-threatening infection with organ dysfunction — initiates a complex interplay of host pro- and anti-inflammatory processes. In a real sense, sepsis can be considered a race to the death between the pathogens and the host immune system. It is the proper balance between the often competing pro- and anti-inflammatory pathways that determines the fate of the individual. Although the field of sepsis research has witnessed the failure of many highly-touted clinical trials, a better understanding of the pathophysiological basis of the disorder and the mechanisms responsible for the associated pro- and anti-inflammatory responses is leading to a novel approach to treat this highly lethal condition. Biomarker-guided immunotherapy administered to patients at the proper immune phase of sepsis represents a potential major advance in the treatment of sepsis and more broadly in the field of infectious disease. PMID:24232462

A Quantitative Evaluation of Dissolved Oxygen Instrumentation

NASA Technical Reports Server (NTRS)

Pijanowski, Barbara S.

1971-01-01

The implications of the presence of dissolved oxygen in water are discussed in terms of its deleterious or beneficial effects, depending on the functional consequences to those affected, e.g., the industrialist, the oceanographer, and the ecologist. The paper is devoted primarily to an examination of the performance of five commercially available dissolved oxygen meters. The design of each is briefly reviewed and ease or difficulty of use in the field described. Specifically, the evaluation program treated a number of parameters and user considerations including an initial check and trial calibration for each instrument and a discussion of the measurement methodology employed. Detailed test results are given relating to the effects of primary power variation, water-flow sensitivity, response time, relative accuracy of dissolved-oxygen readout, temperature accuracy (for those instruments which included this feature), error and repeatability, stability, pressure and other environmental effects, and test results obtained in the field. Overall instrument performance is summarized comparatively by chart.

Reforms speed initiation of NCI-sponsored clinical trials

Cancer.gov

The process of opening a cancer clinical trial for patient accrual often takes years, and research has shown that trials which are slow to register patients often fail to finish. Following a thorough review, NCI’s Operational Efficiency Working Group prod

Current status and perspectives of interventional clinical trials for glioblastoma - analysis of ClinicalTrials.gov.

PubMed

Cihoric, Nikola; Tsikkinis, Alexandros; Minniti, Giuseppe; Lagerwaard, Frank J; Herrlinger, Ulrich; Mathier, Etienne; Soldatovic, Ivan; Jeremic, Branislav; Ghadjar, Pirus; Elicin, Olgun; Lössl, Kristina; Aebersold, Daniel M; Belka, Claus; Herrmann, Evelyn; Niyazi, Maximilian

2017-01-03

The records of 208.777 (100%) clinical trials registered at ClinicalTrials.gov were downloaded on the 19th of February 2016. Phase II and III trials including patients with glioblastoma were selected for further classification and analysis. Based on the disease settings, trials were classified into three groups: newly diagnosed glioblastoma, recurrent disease and trials with no differentiation according to disease setting. Furthermore, we categorized trials according to the experimental interventions, the primary sponsor, the source of financial support and trial design elements. Trends were evaluated using the autoregressive integrated moving average model. Two hundred sixteen (0.1%) trials were selected for further analysis. Academic centers (investigator initiated trials) were recorded as primary sponsors in 56.9% of trials, followed by industry 25.9%. Industry was the leading source of monetary support for the selected trials in 44.4%, followed by 25% of trials with primarily academic financial support. The number of newly initiated trials between 2005 and 2015 shows a positive trend, mainly through an increase in phase II trials, whereas phase III trials show a negative trend. The vast majority of trials evaluate forms of different systemic treatments (91.2%). In total, one hundred different molecular entities or biologicals were identified. Of those, 60% were involving drugs specifically designed for central nervous system malignancies. Trials that specifically address radiotherapy, surgery, imaging and other therapeutic or diagnostic methods appear to be rare. Current research in glioblastoma is mainly driven or sponsored by industry, academic medical oncologists and neuro-oncologists, with the majority of trials evaluating forms of systemic therapies. Few trials reach phase III. Imaging, radiation therapy and surgical procedures are underrepresented in current trials portfolios. Optimization in research portfolio for glioblastoma is needed.

Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma

PubMed Central

Taillibert, Sophie; Kanner, Andrew; Read, William; Steinberg, David M.; Lhermitte, Benoit; Toms, Steven; Idbaih, Ahmed; Ahluwalia, Manmeet S.; Fink, Karen; Di Meco, Francesco; Lieberman, Frank; Zhu, Jay-Jiguang; Stragliotto, Giuseppe; Tran, David D.; Brem, Steven; Hottinger, Andreas F.; Kirson, Eilon D.; Lavy-Shahaf, Gitit; Weinberg, Uri; Kim, Chae-Yong; Paek, Sun-Ha; Nicholas, Garth; Burna, Jordi; Hirte, Hal; Weller, Michael; Palti, Yoram; Hegi, Monika E.; Ram, Zvi

2017-01-01

Importance Tumor-treating fields (TTFields) is an antimitotic treatment modality that interferes with glioblastoma cell division and organelle assembly by delivering low-intensity alternating electric fields to the tumor. Objective To investigate whether TTFields improves progression-free and overall survival of patients with glioblastoma, a fatal disease that commonly recurs at the initial tumor site or in the central nervous system. Design, Setting, and Participants In this randomized, open-label trial, 695 patients with glioblastoma whose tumor was resected or biopsied and had completed concomitant radiochemotherapy (median time from diagnosis to randomization, 3.8 months) were enrolled at 83 centers (July 2009-2014) and followed up through December 2016. A preliminary report from this trial was published in 2015; this report describes the final analysis. Interventions Patients were randomized 2:1 to TTFields plus maintenance temozolomide chemotherapy (n = 466) or temozolomide alone (n = 229). The TTFields, consisting of low-intensity, 200 kHz frequency, alternating electric fields, was delivered (≥ 18 hours/d) via 4 transducer arrays on the shaved scalp and connected to a portable device. Temozolomide was administered to both groups (150-200 mg/m2) for 5 days per 28-day cycle (6-12 cycles). Main Outcomes and Measures Progression-free survival (tested at α = .046). The secondary end point was overall survival (tested hierarchically at α = .048). Analyses were performed for the intent-to-treat population. Adverse events were compared by group. Results Of the 695 randomized patients (median age, 56 years; IQR, 48-63; 473 men [68%]), 637 (92%) completed the trial. Median progression-free survival from randomization was 6.7 months in the TTFields-temozolomide group and 4.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.52-0.76; P < .001). Median overall survival was 20.9 months in the TTFields-temozolomide group vs 16.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.53-0.76; P < .001). Systemic adverse event frequency was 48% in the TTFields-temozolomide group and 44% in the temozolomide-alone group. Mild to moderate skin toxicity underneath the transducer arrays occurred in 52% of patients who received TTFields-temozolomide vs no patients who received temozolomide alone. Conclusions and Relevance In the final analysis of this randomized clinical trial of patients with glioblastoma who had received standard radiochemotherapy, the addition of TTFields to maintenance temozolomide chemotherapy vs maintenance temozolomide alone, resulted in statistically significant improvement in progression-free survival and overall survival. These results are consistent with the previous interim analysis. Trial Registration clinicaltrials.gov Identifier: NCT00916409 PMID:29260225

Field performance of a genetically engineered strain of pink bollworm.

PubMed

Simmons, Gregory S; McKemey, Andrew R; Morrison, Neil I; O'Connell, Sinead; Tabashnik, Bruce E; Claus, John; Fu, Guoliang; Tang, Guolei; Sledge, Mickey; Walker, Adam S; Phillips, Caroline E; Miller, Ernie D; Rose, Robert I; Staten, Robert T; Donnelly, Christl A; Alphey, Luke

2011-01-01

Pest insects harm crops, livestock and human health, either directly or by acting as vectors of disease. The Sterile Insect Technique (SIT)--mass-release of sterile insects to mate with, and thereby control, their wild counterparts--has been used successfully for decades to control several pest species, including pink bollworm, a lepidopteran pest of cotton. Although it has been suggested that genetic engineering of pest insects provides potential improvements, there is uncertainty regarding its impact on their field performance. Discrimination between released and wild moths caught in monitoring traps is essential for estimating wild population levels. To address concerns about the reliability of current marking methods, we developed a genetically engineered strain of pink bollworm with a heritable fluorescent marker, to improve discrimination of sterile from wild moths. Here, we report the results of field trials showing that this engineered strain performed well under field conditions. Our data show that attributes critical to SIT in the field--ability to find a mate and to initiate copulation, as well as dispersal and persistence in the release area--were comparable between the genetically engineered strain and a standard strain. To our knowledge, these represent the first open-field experiments with a genetically engineered insect. The results described here provide encouragement for the genetic control of insect pests.

Relation of initial spacing and relative stand density indices to stand characteristics in a Douglas-fir plantation spacing trial

Treesearch

Robert O. Curtis; Sheel Bansal; Constance A. Harrington

2016-01-01

This report presents updated information on a 1981 Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco var. menziesii ) plantation spacing trial at 33 years from planting. Stand statistics at the most recent measurement were compared for initial spacing of 1 through 6 meters and associated relative densities. There was no clear...

Quantitative evaluation of human cerebellum-dependent motor learning through prism adaptation of hand-reaching movement.

PubMed

Hashimoto, Yuji; Honda, Takeru; Matsumura, Ken; Nakao, Makoto; Soga, Kazumasa; Katano, Kazuhiko; Yokota, Takanori; Mizusawa, Hidehiro; Nagao, Soichi; Ishikawa, Kinya

2015-01-01

The cerebellum plays important roles in motor coordination and learning. However, motor learning has not been quantitatively evaluated clinically. It thus remains unclear how motor learning is influenced by cerebellar diseases or aging, and is related with incoordination. Here, we present a new application for testing human cerebellum-dependent motor learning using prism adaptation. In our paradigm, the participant wearing prism-equipped goggles touches their index finger to the target presented on a touchscreen in every trial. The whole test consisted of three consecutive sessions: (1) 50 trials with normal vision (BASELINE), (2) 100 trials wearing the prism that shifts the visual field 25° rightward (PRISM), and (3) 50 trials without the prism (REMOVAL). In healthy subjects, the prism-induced finger-touch error, i.e., the distance between touch and target positions, was decreased gradually by motor learning through repetition of trials. We found that such motor learning could be quantified using the "adaptability index (AI)", which was calculated by multiplying each probability of [acquisition in the last 10 trials of PRISM], [retention in the initial five trials of REMOVAL], and [extinction in the last 10 trials of REMOVAL]. The AI of cerebellar patients less than 70 years old (mean, 0.227; n = 62) was lower than that of age-matched healthy subjects (0.867, n = 21; p < 0.0001). While AI did not correlate with the magnitude of dysmetria in ataxic patients, it declined in parallel with disease progression, suggesting a close correlation between the impaired cerebellar motor leaning and the dysmetria. Furthermore, AI decreased with aging in the healthy subjects over 70 years old compared with that in the healthy subjects less than 70 years old. We suggest that our paradigm of prism adaptation may allow us to quantitatively assess cerebellar motor learning in both normal and diseased conditions.

Quantitative Evaluation of Human Cerebellum-Dependent Motor Learning through Prism Adaptation of Hand-Reaching Movement

PubMed Central

Hashimoto, Yuji; Honda, Takeru; Matsumura, Ken; Nakao, Makoto; Soga, Kazumasa; Katano, Kazuhiko; Yokota, Takanori; Mizusawa, Hidehiro; Nagao, Soichi; Ishikawa, Kinya

2015-01-01

The cerebellum plays important roles in motor coordination and learning. However, motor learning has not been quantitatively evaluated clinically. It thus remains unclear how motor learning is influenced by cerebellar diseases or aging, and is related with incoordination. Here, we present a new application for testing human cerebellum-dependent motor learning using prism adaptation. In our paradigm, the participant wearing prism-equipped goggles touches their index finger to the target presented on a touchscreen in every trial. The whole test consisted of three consecutive sessions: (1) 50 trials with normal vision (BASELINE), (2) 100 trials wearing the prism that shifts the visual field 25° rightward (PRISM), and (3) 50 trials without the prism (REMOVAL). In healthy subjects, the prism-induced finger-touch error, i.e., the distance between touch and target positions, was decreased gradually by motor learning through repetition of trials. We found that such motor learning could be quantified using the “adaptability index (AI)”, which was calculated by multiplying each probability of [acquisition in the last 10 trials of PRISM], [retention in the initial five trials of REMOVAL], and [extinction in the last 10 trials of REMOVAL]. The AI of cerebellar patients less than 70 years old (mean, 0.227; n = 62) was lower than that of age-matched healthy subjects (0.867, n = 21; p < 0.0001). While AI did not correlate with the magnitude of dysmetria in ataxic patients, it declined in parallel with disease progression, suggesting a close correlation between the impaired cerebellar motor leaning and the dysmetria. Furthermore, AI decreased with aging in the healthy subjects over 70 years old compared with that in the healthy subjects less than 70 years old. We suggest that our paradigm of prism adaptation may allow us to quantitatively assess cerebellar motor learning in both normal and diseased conditions. PMID:25785588

Impact of Magnetic Field on Pressures of Programmable Cerebrospinal Fluid Shunts: An Experimental Study.

PubMed

Altun, Idiris; Yuksel, Kasim Zafer; Mert, Tufan

2017-01-01

To investigate whether programmable cerebrospinal fluid (CSF) shunts are influenced by exposure to the magnetic field and to compare the effects of magnetic field in 4 different brands of programmable CSF shunts. This experimental study was performed in the laboratory using a novel design of magnetic field. Four types of programmable CSF shunts (Miethke®, Medtronic®, Sophysa® and Codman®Hakim®) were exposed to the magnetic field generated by an apparatus consisting of Helmholtz coil for 5 minutes. In every CSF shunt, initial pressures were adjusted to 110 mm H2O and pressures after exposure to magnetic field were noted. These measurements were implemented at frequencies of 5 Hz, 20 Hz, 30 Hz, 40 Hz, 60 Hz and 80 Hz. In each type, three shunts were utilized and evaluations were made twice for every shunt. At 5, 30, 40 and 60 Hz, Groups 1, 2 and 3 had significantly higher average pressures than Group 4. At 20 and 80 Hz, Groups 1 and 2 had notably different pressure values than Groups 3 and 4. Group 3 displayed the highest pressure, while Group 4 demonstrated the lowest pressure. Exposure to magnetic fields may affect the pressures of programmable CSF shunts. However, further controlled, clinical trials are warranted to elucidate the in-vivo effects of magnetic field exposure.

Leishmania Antigenuria to Predict Initial Treatment Failure and Relapse in Visceral Leishmaniasis/HIV Coinfected Patients: An Exploratory Study Nested Within a Clinical Trial in Ethiopia.

PubMed

van Griensven, Johan; Mengesha, Bewketu; Mekonnen, Tigist; Fikre, Helina; Takele, Yegnasew; Adem, Emebet; Mohammed, Rezika; Ritmeijer, Koert; Vogt, Florian; Adriaensen, Wim; Diro, Ermias

2018-01-01

Background: Biomarkers predicting the risk of VL treatment failure and relapse in VL/HIV coinfected patients are needed. Nested within a two-site clinical trial in Ethiopia (2011-2015), we conducted an exploratory study to assess whether (1) levels of Leishmania antigenuria measured at VL diagnosis were associated with initial treatment failure and (2) levels of Leishmania antigenuria at the end of treatment (parasitologically-confirmed cure) were associated with subsequent relapse. Methods: Leishmania antigenuria at VL diagnosis and cure was determined using KAtex urine antigen test and graded as negative (0), weak/moderate (grade 1+/2+) or strongly-positive (3+). Logistic regression and Kaplan-Meier methods were used to assess the association between antigenuria and (1) initial treatment failure, and (2) relapse over the 12 months after cure, respectively. Results: The analysis to predict initial treatment failure included sixty-three coinfected adults [median age: 30 years interquartile range (IQR) 27-35], median CD4 count: 56 cells/μL (IQR 38-113). KAtex results at VL diagnosis were negative in 11 (17%), weak/moderate in 17 (27%) and strongly-positive in 35 (36%). Twenty (32%) patients had parasitologically-confirmed treatment failure, with a risk of failure of 9% (1/11) with KAtex-negative results, 0% (0/17) for KAtex 1+/2+ and 54% (19/35) for KAtex 3+ results. Compared to KAtex-negative patients, KAtex 3+ patients were at increased risk of treatment failure [odds ratio 11.9 (95% CI 1.4-103.0); P : 0.025]. Forty-four patients were included in the analysis to predict relapse [median age: 31 years (IQR 28-35), median CD4 count: 116 cells/μL (IQR 95-181)]. When achieving VL cure, KAtex results were negative in 19 (43%), weak/moderate (1+/2+) in 10 (23%), and strongly positive (3+) in 15 patients (34%). Over the subsequent 12 months, eight out of 44 patients (18%) relapsed. The predicted 1-year relapse risk was 6% for KAtex-negative results, 14% for KAtex 1+/2+ and 42% for KAtex 3+ results [hazard ratio of 2.2 (95% CI 0.1-34.9) for KAtex 1+/2+ and 9.8 (95% CI 1.8-82.1) for KAtex 3+, compared to KAtex negative patients; P : 0.03]. Conclusion: A simple field-deployable Leishmania urine antigen test can be used for risk stratification of initial treatment failure and VL relapse in HIV-patients. A dipstick-format would facilitate field implementation.

ELECTROCHEMICAL ARSENIC REMEDIATION IN RURAL BANGLADESH

EPA Science Inventory

In Year 1, we built a bench-scale continuous flow prototype (dubbed “Sushi” for its sushi-like electrode roll) and completed preliminary field trials in Bangladesh. We were also able to leverage additional funding to complete preliminary field trials in arsenic-...

Application of Biomarkers in the Development of Drugs Intended for the Treatment of Osteoarthritis

PubMed Central

Kraus, Virginia Byers; Burnett, Bruce; Coindreau, Javier; Cottrell, Susan; Eyre, David; Gendreau, Michael; Gardiner, Jennifer; Garnero, Patrick; Hardin, John; Henrotin, Yves; Heinegård, Dick; Ko, Amy; Lohmander, Stefan; Matthews, Gloria; Menetski, Joseph; Moskowitz, Roland; Persiani, Stefano; Poole, Robin; Rousseau, Jean Charles; Todman, Martin

2013-01-01

Objective Osteoarthritis (OA) is a chronic and slowly progressive disease for which biomarkers may be able to provide a more rapid indication of therapeutic responses to therapy than is currently available; this could accelerate and facilitate OA drug discovery and development programs. The goal of this document is to provide a summary and guide to the application of in vitro (biochemical and other soluble) biomarkers in the development of drugs for OA and to outline and stimulate a research agenda that will further this goal. Methods The Biomarkers Working Group representing experts in the field of OA biomarker research from both academia and industry developed this consensus document between 2007–2009 at the behest of the Osteoarthritis Research Society International (OARSI FDA initiative). Results This document summarizes definitions and classification systems for biomarkers, the current outcome measures used in OA clinical trials, applications and potential utility of biomarkers for development of OA therapeutics, the current state of qualification of OA-related biomarkers, pathways for biomarker qualification, critical needs to advance the use of biomarkers for drug development, recommendations regarding practices and clinical trials, and a research agenda to advance the science of OA-related biomarkers. Conclusions Although many OA-related biomarkers are currently available they exist in various states of qualification and validation. The biomarkers that are likely to have the earliest beneficial impact on clinical trials fall into two general categories, those that will allow targeting of subjects most likely to either respond and/or progress (prognostic value) within a reasonable and manageable time frame for a clinical study (for instance within one to two years for an OA trial), and those that provide early feedback for preclinical decision-making and for trial organizers that a drug is having the desired biochemical effect. As in vitro biomarkers are increasingly investigated in the context of specific drug treatments, advances in the field can be expected that will lead to rapid expansion of the list of available biomarkers with increasing understanding of the molecular processes that they represent. PMID:21396468

Five-year field trials using preservative-treated, second-growth Douglas-fir exposed in ground contact in Australia

Treesearch

Rodney C. De Groot; Douglas M. Crawford; Jack Norton; John Keith

2000-01-01

The durability of preservative-treated stakes of second-growth Coastal Douglas-fir was evaluated in a field plot in northern Queensland, Australia. Results from this field trial indicate that second-growth Douglas-fir can be treated with preservatives to meet Australian standards and will provide long-term durability in adverse environments. Data presented indicate...

Renal denervation: What happened, and why?

PubMed

Shishehbor, Mehdi H; Hammad, Tarek A; Thomas, George

2017-09-01

Despite promising results in initial trials, renal denervation failed to achieve its efficacy end points as a treatment for resistant hypertension in the SYMPLICITY HTN-3 trial, the largest trial of this treatment to date (N Engl J Med 2014; 370:1393-1401). Is renal denervation dead, or will future trials and newer technology revive it? Copyright © 2017 Cleveland Clinic.

PILOT TESTING: PRETREATMENT OPTIONS TO ALLOW RE-USE OF FRAC FLOWBACK AND PRODUCED BRINE FOR GAS SHALE RESOURCE DEVELOPMENT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burnett, David

2012-12-31

The goal of the A&M DOE NETL Project No. DE-FE0000847 was to develop a mobile, multifunctional water treatment capability designed specifically for “pre-treatment” of field waste brine. The project consisted of constructing s mobile “field laboratory” incorporating new technology for treating high salinity produced water and using the lab to conduct a side-by-side comparison between this new technology and that already existing in field operations. A series of four field trials were performed utilizing the mobile unit to demonstrate the effectiveness of different technology suitable for use with high salinity flow back brines and produced water. The design of themore » mobile unit was based on previous and current work at the Texas A&M Separation Sciences Pilot Plant. The several treatment techniques which have been found to be successful in both pilot plant and field tests had been tested to incorporate into a single multifunctional process train. Eight different components were evaluated during the trials, two types of oil and grease removal, one BTEX removal step, three micro-filters, and two different nanofilters. The performance of each technique was measured by its separation efficiency, power consumption, and ability to withstand fouling. The field trials were a success. Four different field brines were evaluated in the first trial in New York. Over 16,000 gallons of brine were processed. Using a power cost of $.10 per kWh, media pretreatment power use averaged $0.004 per barrel, solids removal $.04 per barrel and brine “softening” $.84 per barrel. Total power cost was approximately $1.00 per barrel of fluid treated. In Pennsylvania, brines collected from frac ponds were tested in two additional trials. Each of the brines was converted to an oil-free, solids-free brine with no biological activity. Brines were stable over time and would be good candidates for use as a make-up fluid in a subsequent fracturing fluid design. Reports on all of the field trials and subcontractor research have been summarized in this Final Report. Individual field trial reports and research reports are contained in the companion volume titled “Appendices”« less

Chemoprevention with special reference to inherited colorectal cancer.

PubMed

Lynch, Patrick M

2008-01-01

Familial Adenomatous Polyposis (FAP) is a model for the adenoma-carcinoma sequence in several respects. One important area in which FAP serves as a model is chemoprevention. Early prevention trials mainly utilized micronutrients and were largely unsuccessful in preventing or causing regression of adenomas. A new era was ushered in by the recognition that antiarthritic doses of a nonsteroidal anti-inflammatory agent (NSAID), sulindac, could actually induce regression of colorectal adenomas in patients with FAP. Follow-up studies showed positive but variable long-term efficacy for colorectal adenomas, but sulindac appears to lack significant benefit in regressing duodenal adenomas or preventing initial occurrence of adenomas in APC mutation carriers. Due to the well-known side effects of traditional NSAIDs, selective COX-2 inhibitors have been studied rather extensively. Celecoxib has shown benefit in regressing colorectal adenomas and appears to have some duodenal activity as well. Rofecoxib, in smaller trials, showed efficacy as well. However, the entire field of NSAID research in chemoprevention is undergoing reexamination in light of recent demonstration of cardiovascular toxicity in nonfamilial or sporadic adenoma prevention trials. Whether NSAIDs will have a significant future in FAP chemoprevention will depend on a sober assessment of risks and benefits. These same issues will likely foster a more intensive search for new agents. FAP will undoubtedly continue to have a lead role in the testing of new agents, both in the interest of FAP management as such, and in anticipation of trials in nonfamilial adenomas, a problem with even greater societal impact. The historical development of chemoprevention in FAP will be presented, with an emphasis on issues of trial design.

76 FR 38037 - Mevinphos; Data Call-in Order for Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-29

... residues of mevinphos on the following commodities: Broccoli, cabbage, cauliflower, celery, spinach... Field Trials (860.1500)--(broccoli, cabbage, cauliflower, celery, grapes, lettuce, peas, peppers... Not required October 1, 2012. 860.1500 Crop Field Trials Not Required September 30, 2013. (broccoli...

RApid Primary care Initiation of Drug treatment for Transient Ischaemic Attack (RAPID−TIA): study protocol for a pilot randomised controlled trial

PubMed Central

2013-01-01

Background People who have a transient ischaemic attack (TIA) or minor stroke are at high risk of a recurrent stroke, particularly in the first week after the event. Early initiation of secondary prevention drugs is associated with an 80% reduction in risk of stroke recurrence. This raises the question as to whether these drugs should be given before being seen by a specialist – that is, in primary care or in the emergency department. The aims of the RAPID-TIA pilot trial are to determine the feasibility of a randomised controlled trial, to analyse cost effectiveness and to ask: Should general practitioners and emergency doctors (primary care physicians) initiate secondary preventative measures in addition to aspirin in people they see with suspected TIA or minor stroke at the time of referral to a specialist? Methods/Design This is a pilot randomised controlled trial with a sub-study of accuracy of primary care physician diagnosis of TIA. In the pilot trial, we aim to recruit 100 patients from 30 general practices (including out-of-hours general practice centres) and 1 emergency department whom the primary care physician diagnoses with TIA or minor stroke and randomly assign them to usual care (that is, initiation of aspirin and referral to a TIA clinic) or usual care plus additional early initiation of secondary prevention drugs (a blood-pressure lowering protocol, simvastatin 40 mg and dipyridamole 200 mg m/r bd). The primary outcome of the main study will be the number of strokes at 90 days. The diagnostic accuracy sub-study will include these 100 patients and an additional 70 patients in whom the primary care physician thinks the diagnosis of TIA is possible, rather than probable. For the pilot trial, we will report recruitment rate, follow-up rate, a preliminary estimate of the primary event rate and occurrence of any adverse events. For the diagnostic study, we will calculate sensitivity and specificity of primary care physician diagnosis using the final TIA clinic diagnosis as the reference standard. Discussion This pilot study will be used to estimate key parameters that are needed to design the main study and to estimate the accuracy of primary care diagnosis of TIA. The planned follow-on trial will have important implications for the initial management of people with suspected TIA. Trial registration ISRCTN62019087 PMID:23819476

RApid Primary care Initiation of Drug treatment for Transient Ischaemic Attack (RAPID-TIA): study protocol for a pilot randomised controlled trial.

PubMed

Edwards, Duncan; Fletcher, Kate; Deller, Rachel; McManus, Richard; Lasserson, Daniel; Giles, Matthew; Sims, Don; Norrie, John; McGuire, Graham; Cohn, Simon; Whittle, Fiona; Hobbs, Vikki; Weir, Christopher; Mant, Jonathan

2013-07-02

People who have a transient ischaemic attack (TIA) or minor stroke are at high risk of a recurrent stroke, particularly in the first week after the event. Early initiation of secondary prevention drugs is associated with an 80% reduction in risk of stroke recurrence. This raises the question as to whether these drugs should be given before being seen by a specialist--that is, in primary care or in the emergency department. The aims of the RAPID-TIA pilot trial are to determine the feasibility of a randomised controlled trial, to analyse cost effectiveness and to ask: Should general practitioners and emergency doctors (primary care physicians) initiate secondary preventative measures in addition to aspirin in people they see with suspected TIA or minor stroke at the time of referral to a specialist? This is a pilot randomised controlled trial with a sub-study of accuracy of primary care physician diagnosis of TIA. In the pilot trial, we aim to recruit 100 patients from 30 general practices (including out-of-hours general practice centres) and 1 emergency department whom the primary care physician diagnoses with TIA or minor stroke and randomly assign them to usual care (that is, initiation of aspirin and referral to a TIA clinic) or usual care plus additional early initiation of secondary prevention drugs (a blood-pressure lowering protocol, simvastatin 40 mg and dipyridamole 200 mg m/r bd). The primary outcome of the main study will be the number of strokes at 90 days. The diagnostic accuracy sub-study will include these 100 patients and an additional 70 patients in whom the primary care physician thinks the diagnosis of TIA is possible, rather than probable. For the pilot trial, we will report recruitment rate, follow-up rate, a preliminary estimate of the primary event rate and occurrence of any adverse events. For the diagnostic study, we will calculate sensitivity and specificity of primary care physician diagnosis using the final TIA clinic diagnosis as the reference standard. This pilot study will be used to estimate key parameters that are needed to design the main study and to estimate the accuracy of primary care diagnosis of TIA. The planned follow-on trial will have important implications for the initial management of people with suspected TIA. ISRCTN62019087.

TRENDS IN USE OF EZETIMIBE AFTER THE ENHANCE TRIAL, 2007–2010

PubMed Central

Ross, Joseph S.; Frazee, Sharon G.; Garavaglia, Susan B.; Levin, Rebecca; Novshadian, Haik; Jackevicius, Cynthia A.; Stettin, Glen; Krumholz, Harlan M.

2014-01-01

Importance Results from the landmark Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression [ENHANCE] trial were announced in January 2008, demonstrating that ezetimibe lowered cholesterol levels but did not slow the progression of atherosclerosis. Objective Examine the association of this announcement with national patterns of ezetimibe prescribing, including medication initiation and discontinuation, as well as predictors of use. Design, Setting and Patients Retrospective analysis of a national sample of adults aged 18 years or older who were continuously enrolled in a large U.S. pharmacy benefit manager from 2007 to 2010. Main Outcome Measures All lipid-lowering therapy prescription claims were categorized as ezetimibe-containing treatments or any other lipid-lowering agent. Initiation was defined as an ezetimibe claim without another in the prior 180 days; discontinuation as an ezetimibe claim without another in the subsequent 180 days. Results From 2007 to 2010, there were 10 million continuously eligible adults, 29.1% of whom obtained at least one prescription for a lipid-lowering agent. Among these adults, 17.8% were prescribed ezetimibe, 95.3% another lipid-lowering agent, predominantly statins. Ezetimibe use peaked in January 2008, when 2.5% of all adults were ezetimibe users, but declined only to 1.8% by December 2010. Although announcement of the ENHANCE trial was not associated with a significant change in overall ezetimibe use (p=0.11), it was associated with significantly more monthly monotherapy use and significantly less monthly ezetimibe use concomitant with other lipid-lowering agents. The ENHANCE trial was also associated with significantly fewer ezetimibe initiations (p=0.002) and significantly more ezetimibe discontinuations (p<0.0001), particularly of ezetimibe monotherapy for both. Before and after the trial, more than half of adults who initiated ezetimibe did so without first being prescribed another lipid-lowering agent. Middle aged adults (50 and 64 years) and those living in the East South Central United States were both more likely to initiate and less likely to discontinue ezetimibe after the ENHANCE trial. Conclusions After announcement of the results of the ENHANCE trial, nearly 2% of all continuously enrolled adult beneficiaries within a large U.S. pharmacy benefit manager used ezetimibe, although ezetimibe initiations declined and discontinuations increased. PMID:25070672

Ethical issues in field trials of genetically modified disease-resistant mosquitoes.

PubMed

Resnik, David B

2014-04-01

Mosquito-borne diseases take a tremendous toll on human populations, especially in developing nations. In the last decade, scientists have developed mosquitoes that have been genetically modified to prevent transmission of mosquito-borne diseases, and field trials have been conducted. Some mosquitoes have been rendered infertile, some have been equipped with a vaccine they transmit to humans, and some have been designed to resist diseases. This article focuses on ethical issues raised by field trials of disease-resistant, genetically modified mosquitoes. Some of these issues include: protecting the public and the environment from harm, balancing benefits and risks, collaborating with the local community, avoiding exploitation, and safeguarding the rights and welfare of research subjects. One of the most difficult problems involves protecting the welfare of community members who will be impacted by the release of mosquitoes but who are not enrolled in the study as research subjects. To address this concern, field trials should take place only when the targeted disease is a significant public health problem in an isolated area, the benefits of the trial for the community are likely to outweigh the risks, community leaders approve of the trial, and there are measures in place to protect the welfare of un-enrolled community members, such as informing the community about the study and offering free treatment to people who contract mosquito-borne diseases. Since the justification of any field trial depends on a careful examination of the scientific and ethical issues, proposed studies should be evaluated on a case-by-case basis. Published 2012. This article is a US Government work and is in the public domain in the USA.

Universal testing and treatment as an HIV prevention strategy: research questions and methods.

PubMed

Hayes, Richard; Sabapathy, Kalpana; Fidler, Sarah

2011-09-01

Achieving high coverage of antiretroviral treatment (ART) in resource-poor settings will become increasingly difficult unless HIV incidence can be reduced substantially. Universal voluntary counselling and testing followed by immediate initiation of ART for all those diagnosed HIV-positive (universal testing and treatment, UTT) has the potential to reduce HIV incidence dramatically but would be very challenging and costly to deliver in the short term. Early modelling work in this field has been criticised for making unduly optimistic assumptions about the uptake and coverage of interventions. In future work, it is important that model parameters are realistic and based where possible on empirical data. Rigorous research evidence is needed before the UTT approach could be considered for wide-scale implementation. This paper reviews the main areas that need to be explored. We consider in turn research questions related to the provision of services for universal testing, services for immediate treatment of HIV-positives and the population-level impact of UTT, and the research methods that could be used to address these questions. Ideally, initial feasibility studies should be carried out to investigate the acceptability, feasibility and uptake of UTT services. If these studies produce promising results, there would be a strong case for a cluster-randomised trial to measure the impact of a UTT intervention on HIV incidence, and we consider the main design features of such a trial.

Antibiotics for the neurological complications of Lyme disease.

PubMed

Cadavid, Diego; Auwaerter, Paul G; Rumbaugh, Jeffrey; Gelderblom, Harald

2016-12-08

Various central nervous system-penetrant antibiotics are bactericidal in vitro and in vivo against the causative agent of Lyme neuroborreliosis (LNB), Borrelia burgdorferi. These antibiotics are routinely used clinically to treat LNB, but their relative efficacy is not clear. To assess the effects of antibiotics for the treatment of LNB. On 25 October 2016 we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase. We searched clinical trial registers on 26 October 2016. We reviewed the bibliographies of the randomized trials identified and contacted the authors and known experts in the field to identify additional published or unpublished data. There were no language restrictions when searching for studies. Randomized clinical trials of antibiotic treatment of LNB in adults and children that compared any antibiotic treatment, including combinations of treatments, versus any other treatment, placebo, or no treatment. We excluded studies of entities considered as post-Lyme syndrome. We used standard methodological procedures expected by Cochrane. We identified seven randomized studies involving 450 European participants with LNB for inclusion in this systematic review. We found no trials conducted in the United States. Marked heterogeneity among these studies prevented meta-analysis. None of the studies included a placebo control on the initial antibiotic treatment, and only one was blinded. None were delayed-start studies. All were active comparator studies, and most were not adequately powered for non-inferiority comparison. The trials investigated four antibiotics: penicillin G and ceftriaxone in four studies, doxycycline in three studies, and cefotaxime in two studies. One study tested a three-month course of oral amoxicillin versus placebo following initial treatment with intravenous ceftriaxone. One study was limited to children. The trials measured efficacy using heterogeneous physician- or patient-reported outcomes, or both. In some cases cerebrospinal fluid analysis was included as an indirect biomarker of disease and outcome. None of the studies reported on our proposed primary outcome, 'Improvement in a measure of overall disability in the long term (three or more months).' None of the trials revealed any between-group differences in symptom resolution in response to active treatment. In general, treatment was tolerated well. The quality of adverse event reporting, however, was low. There is mostly low- to very low-quality clinical evidence from a limited number of mostly small, heterogeneous trials with diverse outcome measures, comparing the relative efficacy of central nervous system-penetrant antibiotics for the treatment of LNB. The few existing randomized studies have limited power and lack consistent and well-defined entry criteria and efficacy endpoints. It is not possible to draw firm conclusions on the relative efficacy of accepted antibiotic drug regimens for the treatment of LNB. The majority of people are reported to have good outcomes, and symptoms resolve by 12 months regardless of the antibiotic used. A minority of participants did not improve sufficiently, and some were retreated. These randomized studies provide some evidence that doxycycline, penicillin G, ceftriaxone, and cefotaxime are efficacious in the treatment of European LNB. No evidence of additional efficacy was observed when, in one study, an initial antibiotic treatment with intravenous ceftriaxone was followed by additional longer treatment with oral amoxicillin. There is a lack of evidence identified through our high-quality search strategy on the efficacy of antibiotics for treatment of LNB in the United States.

Two field trials for deblending of simultaneous source surveys: Why we failed and why we succeeded?

NASA Astrophysics Data System (ADS)

Zu, Shaohuan; Zhou, Hui; Chen, Haolin; Zheng, Hao; Chen, Yangkang

2017-08-01

Currently, deblending is the main strategy for dealing with the intense interference problem of simultaneous source data. Most deblending methods are based on the property that useful signal is coherent while the interference is incoherent in some domains other than common shot domain. In this paper, two simultaneous source field trials were studied in detail. In the first trial, the simultaneous source survey was not optimal, as the dithering code had strong coherency and the minimum distance between the two vessels was also small. The chosen marine shot scheduling and vessel deployment made it difficult to deblend the simultaneous source data, and result was an unexpected failure. Next, we tested different parameters (the dithering code and the minimum distance between vessels) of the simultaneous source survey using the simulated blended data and got some useful insights. Then, we carried out the second field trial with a carefully designed survey that was much different from the first trial. The deblended results in common receiver gather, common shot gather or the final stacked profile were encouraging. We obtained a complete success in the second field trial, which gave us confidence in the further test (such as a full three dimensional acquisition test or a high-resolution acquisition test with denser spatial sampling). Remembering that failures with simultaneous sourcing seldom reported, in this paper, our contribution is the discussion in detail about both our failed and successful field experiments and the lessons we have learned from them with the hope that the experience gained from this study can be very useful to other researchers in the same field.

Disruption of Darna pallivitta (Lepidoptera: Limacodidae) by Conventional and Mobile Pheromone Deployment

PubMed Central

Siderhurst, Matthew S.; Jang, Eric B.; Carvalho, Lori A. F. N.; Nagata, Janice T.; Derstine, Nathan T.

2015-01-01

Identification of the Darna pallivitta (Moore) pheromone component n-butyl (E)-7,9-decadienoate (E7,9-10:COOn-Bu) has made it possible to investigate communication disruption to control this lepidopteran pest. Conventional communication disruption trials showed marked decreases in the mean number of male moths captured in E7,9-10:COOnBu-treated fields compared with control fields. For traps baited with E7,9-10:COOnBu, percent disruptions were 94.4% and 92.1% for septa (1 g pheromone/ha, 1-wk trial duration) and spirals (6 g pheromone/ha, 8-wk trial duration) respectively. For traps baited with virgin female moths, percent disruption was 73.3% using septa disruptors (1 g pheromone/ha, 1-wk trial duration). Mobile communication disruption using Bactrocera cucurbitae (Coquillett) as carriers for E7,9-10:COOn-Bu was evaluated in the following three areas: fly survivorship, attraction of male moths to treated flies, and moth disruption in a small-scale field trial. Topical application of E7,9-10:COOnBu showed no significant decrease in survivorship at 50 and 80 µg/fly. However, decreased survivorship was observed at 100 µg/fly and linear regression showed E7,9-10:COOnBu dose was significantly correlated with B. cucurbitae survivorship. Traps containing honey–pheromone-fed flies attracted and caught D. pallivitta over a 1-wk period, demonstrating the attractiveness of the carrier. Releasing E7,9-10:COOnBu-fed B. cucurbitae (∼2 g pheromone/ha, 1-wk trial duration) resulted in significantly reduced trap catches in treatment fields compared with control fields on the first 2 d of the field trial. Percent disruptions were 84.7% (day 1) and 56.0% (day 2). These results suggest that both conventional communication disruption and mobile communication disruption have potential to control D. pallivitta. PMID:26078301

Disruption of Darna pallivitta (Lepidoptera: Limacodidae) by Conventional and Mobile Pheromone Deployment.

PubMed

Siderhurst, Matthew S; Jang, Eric B; Carvalho, Lori A F N; Nagata, Janice T; Derstine, Nathan T

2015-01-01

Identification of the Darna pallivitta (Moore) pheromone component n-butyl (E)-7,9-decadienoate (E7,9-10:COOn-Bu) has made it possible to investigate communication disruption to control this lepidopteran pest. Conventional communication disruption trials showed marked decreases in the mean number of male moths captured in E7,9-10:COOnBu-treated fields compared with control fields. For traps baited with E7,9-10:COOnBu, percent disruptions were 94.4% and 92.1% for septa (1 g pheromone/ha, 1-wk trial duration) and spirals (6 g pheromone/ha, 8-wk trial duration) respectively. For traps baited with virgin female moths, percent disruption was 73.3% using septa disruptors (1 g pheromone/ha, 1-wk trial duration). Mobile communication disruption using Bactrocera cucurbitae (Coquillett) as carriers for E7,9-10:COOn-Bu was evaluated in the following three areas: fly survivorship, attraction of male moths to treated flies, and moth disruption in a small-scale field trial. Topical application of E7,9-10:COOnBu showed no significant decrease in survivorship at 50 and 80 µg/fly. However, decreased survivorship was observed at 100 µg/fly and linear regression showed E7,9-10:COOnBu dose was significantly correlated with B. cucurbitae survivorship. Traps containing honey-pheromone-fed flies attracted and caught D. pallivitta over a 1-wk period, demonstrating the attractiveness of the carrier. Releasing E7,9-10:COOnBu-fed B. cucurbitae (∼2 g pheromone/ha, 1-wk trial duration) resulted in significantly reduced trap catches in treatment fields compared with control fields on the first 2 d of the field trial. Percent disruptions were 84.7% (day 1) and 56.0% (day 2). These results suggest that both conventional communication disruption and mobile communication disruption have potential to control D. pallivitta. © The Author 2015. Published by Oxford University Press on behalf of the Entomological Society of America.

Comparing Web-Based Provider-Initiated and Patient-Initiated Survivorship Care Planning for Cancer Patients: A Randomized Controlled Trial

PubMed Central

Tolbert, Elliott; Hannum, Susan M; Radhakrishnan, Archana; Zorn, Kelsey; Blackford, Amanda; Greco, Stephen; Smith, Karen; Snyder, Claire F

2016-01-01

Background Survivorship care plans (SCPs) are intended to facilitate communication and coordination between patients, oncologists, and primary care providers. Most SCP initiatives have focused on oncology providers initiating the SCP process, but time and resource barriers have limited uptake. Objective This trial compares the feasibility and value of 2 Web-based SCP tools: provider-initiated versus patient-initiated. Methods This mixed-methods study recruited clinicians from 2 academically-affiliated community oncology practices. Eligible patients were treated by a participating oncologist, had nonmetastatic cancer, completed acute treatment ≤ 2 months before enrollment, and had no evidence of disease. Patients were randomized 1:1 to either provider-initiated or patient-initiated SCPs—both are Web-based tools. We conducted qualitative interviews with providers at baseline and follow-up and with patients 2 months after enrollment. In addition, patients were administered the Preparing for Life as a (New) Survivor (PLANS) and Cancer Survivors’ Unmet Needs (CaSUN) surveys at baseline and 2 months. Results A total of 40 providers were approached for the study, of whom 13 (33%) enrolled. Providers or clinic staff required researcher assistance to identify eligible patients; 41 patients were randomized, of whom 25 completed follow-up (61%; 13 provider-initiated, 12 patient-initiated). Of the 25, 11 (44%) had initiated the SCP; 5 (20%) provided the SCP to their primary care provider. On the Preparing for Life as a (New) Survivor and Cancer Survivors’ Unmet Needs, patients in both arms tended to report high knowledge and confidence and few unmet needs. In qualitative interviews, providers and patients discussed SCPs’ value. Conclusions Regardless of patient- versus provider-initiated templates and the Web-based design of these tools, barriers to survivorship care planning persist. Further efforts should emphasize workflow functions for identifying and completing SCPs—regardless of the SCP form used. Trial Registration ClinicalTrials.gov NCT02405819; https://clinicaltrials.gov/ct2/show/NCT02405819 (Archived by WebCite at http://www.webcitation.org/6jWqcWOvK) PMID:28410187

Behavioral evidence for a magnetic sense in the oriental armyworm, Mythimna separata

PubMed Central

Xu, Jingjing; Zhang, Yingchao; Li, Yue; Wan, Guijun; Chen, Fajun; Sword, Gregory A.; Pan, Weidong

2017-01-01

ABSTRACT Progress has been made in understanding the mechanisms underlying directional navigation in migratory insects, yet the magnetic compass involved has not been fully elucidated. Here we developed a flight simulation system to study the flight directionality of the migratory armyworm Mythimna separata in response to magnetic fields. Armyworm moths were exposed to either a 500 nT extreme weak magnetic field, 1.8 T strong magnetic field, or a deflecting magnetic field and subjected to tethered flight trials indoors in the dark. The moths were disoriented in the extreme weak magnetic field, with flight vectors that were more dispersed (variance=0.60) than in the geomagnetic field (variance=0.32). After exposure to a 1.8 T strong magnetic field, the mean flight vectors were shifted by about 105° in comparison with those in the geomagnetic field. In the deflecting magnetic field, the flight directions varied with the direction of the magnetic field, and also pointed to the same direction of the magnetic field. In the south-north magnetic field and the east-west field, the flight angles were determined to be 98.9° and 166.3°, respectively, and formed the included angles of 12.66° or 6.19° to the corresponding magnetic direction. The armyworm moths responded to the change of the intensity and direction of magnetic fields. Such results provide initial indications of the moth reliance on a magnetic compass. The findings support the hypothesis of a magnetic sense used for flight orientation in the armyworm Mythimna separata. PMID:28126710

A technique to train new oculomotor behavior in patients with central macular scotomas during reading related tasks using scanning laser ophthalmoscopy: immediate functional benefits and gains retention.

PubMed

Déruaz, Anouk; Goldschmidt, Mira; Whatham, Andrew R; Mermoud, Christophe; Lorincz, Erika N; Schnider, Armin; Safran, Avinoam B

2006-11-23

Reading with a central scotoma involves the use of preferred retinal loci (PRLs) that enable both letter resolution and global viewing of word. Spontaneously developed PRLs however often privilege spatial resolution and, as a result, visual span is commonly limited by the position of the scotoma. In this study we designed and performed the pilot trial of a training procedure aimed at modifying oculomotor behavior in subjects with central field loss. We use an additional fixation point which, when combined with the initial PRL, allows the fulfillment of both letter resolution and global viewing of words. The training procedure comprises ten training sessions conducted with the scanning laser ophthalmoscope (SLO). Subjects have to read single letters and isolated words varying in length, by combining the use of their initial PRL with the one of an examiner's selected trained retinal locus (TRL). We enrolled five subjects to test for the feasibility of the training technique. They showed stable maculopathy and persisting major reading difficulties despite previous orthoptic rehabilitation. We evaluated ETDRS visual acuity, threshold character size for single letters and isolated words, accuracy for paragraphed text reading and reading strategies before, immediately after SLO training, and three months later. Training the use of multiple PRLs in patients with central field loss is feasible and contributes to adapt oculomotor strategies during reading related tasks. Immediately after SLO training subjects used in combination with their initial PRL the examiner's selected TRL and other newly self-selected PRLs. Training gains were also reflected in ETDRS acuity, threshold character size for words of different lengths and in paragraphed text reading. Interestingly, subjects benefited variously from the training procedure and gains were retained differently as a function of word length. We designed a new procedure for training patients with central field loss using scanning laser ophthalmoscopy. Our initial results on the acquisition of newly self-selected PRLs and the development of new oculomotor behaviors suggest that the procedure aiming primarily at developing an examiner's selected TRL might have initiated a more global functional adaptation process.

Theory-based interventions for contraception.

PubMed

Lopez, Laureen M; Tolley, Elizabeth E; Grimes, David A; Chen-Mok, Mario

2011-03-16

The explicit use of theory in research helps expand the knowledge base. Theories and models have been used extensively in HIV-prevention research and in interventions for preventing sexually transmitted infections (STIs). The health behavior field uses many theories or models of change. However, educational interventions addressing contraception often have no stated theoretical base. Review randomized controlled trials (RCTs) that tested a theoretical approach to inform contraceptive choice; encourage contraceptive use; or promote adherence to, or continuation of, a contraceptive regimen. We searched computerized databases for trials that tested a theory-based intervention for improving contraceptive use (MEDLINE, POPLINE, CENTRAL, PsycINFO, EMBASE, ClinicalTrials.gov, and ICTRP). We also wrote to researchers to find other trials. Trials tested a theory-based intervention for improving contraceptive use. We excluded trials focused on high-risk groups and preventing sexually transmitted infections or HIV. Interventions addressed the use of one or more contraceptive methods for contraception. The reports provided evidence that the intervention was based on a specific theory or model. The primary outcomes were pregnancy, contraceptive choice, initiating or changing contraceptive use, contraceptive regimen adherence, and contraception continuation. The primary author evaluated abstracts for eligibility. Two authors extracted data from included studies. We calculated the odds ratio for dichotomous outcomes. No meta-analysis was conducted due to intervention differences. Fourteen RCTs met our inclusion criteria. In 2 of 10 trials with pregnancy or birth data, a theory-based group showed better results. Four of 10 trials with contraceptive use data (other than condoms) showed better outcomes in an experimental group. For condom use, a theory-based group had favorable results in three of eight trials. Social Cognitive Theory was the main theoretical basis for five trials, of which three showed positive results. Two based on other social cognition models had favorable results, as did two of four focused on motivational interviewing. Thirteen trials provided multiple sessions or contacts. Of seven effective interventions, five targeted adolescents, including four with group sessions. Three effective trials had individual sessions. Seven trials were rated as having high or moderate quality; three of those had favorable results. Family planning researchers and practitioners could adapt the effective interventions. Reproductive health needs high-quality research on behavior change, especially for clinical and low-resource settings. More thorough use of single theories would help, as would better reporting on research design and intervention implementation.

Left-handers look before they leap: handedness influences reactivity to novel Tower of Hanoi tasks

PubMed Central

Wright, Lynn; Hardie, Scott M.

2015-01-01

A sample of 203 task naïve left- and right-handed participants were asked to complete a combination of the 3- and 4-disk Towers of Hanoi (ToH), manipulating novelty and complexity. Self-reported state anxiety and latency to respond (initiation time) were recorded before each ToH. Novelty had a major effect on initiation time, particularly for left-handers. Left-handers had a longer latency to start and this was significantly longer on the first trial. Irrespective of hand-preference, initiation time reduced on the second trial, however, this was greatest for left-handers. Condition of task did not systematically influence initiation time for right handers, but did for left-handers. State anxiety was influenced by task novelty and complexity in a more complicated way. During the first trial, there was a significant handedness × number of disks interaction with left-handers having significantly higher state anxiety levels before the 3-disk ToH. This suggests that the initial reaction to this task for left-handers was not simply due to perceived difficulty. On their second trial, participants completing a novel ToH had higher state anxiety scores than those completing a repeated version. Overall, left-handers had a larger reduction in their state anxiety across trials. Relating to this, the expected strong positive correlation between state and trait anxiety was absent for left-handed females in their first tower presentation, but appeared on their second. This was driven by low trait anxiety individuals showing a higher state anxiety response in the first (novel) trial, supporting the idea that left-handed females respond to novelty in a way that is not directly a consequence of their trait anxiety. A possible explanation may be stereotype threat influencing the behavior of left-handed females. PMID:25691878

Supporting open access to clinical trial data for researchers: The Duke Clinical Research Institute-Bristol-Myers Squibb Supporting Open Access to Researchers Initiative.

PubMed

Pencina, Michael J; Louzao, Darcy M; McCourt, Brian J; Adams, Monique R; Tayyabkhan, Rehbar H; Ronco, Peter; Peterson, Eric D

2016-02-01

There are growing calls for sponsors to increase transparency by providing access to clinical trial data. In response, Bristol-Myers Squibb and the Duke Clinical Research Institute have collaborated on a new initiative, Supporting Open Access to Researchers. The aim is to facilitate open sharing of Bristol-Myers Squibb trial data with interested researchers. Key features of the Supporting Open Access to Researchers data sharing model include an independent review committee that ensures expert consideration of each proposal, stringent data deidentification/anonymization and protection of patient privacy, requirement of prespecified statistical analysis plans, and independent review of manuscripts before submission for publication. We believe that these approaches will promote open science by allowing investigators to verify trial results as well as to pursue interesting secondary uses of trial data without compromising scientific integrity. Copyright © 2015 Elsevier Inc. All rights reserved.

Design and Implementation of the Resuscitation Outcomes Consortium Pragmatic Airway Resuscitation Trial (PART)

PubMed Central

Wang, Henry E.; Prince, David; Stephens, Shannon W.; Herren, Heather; Daya, Mohamud; Richmond, Neal; Carlson, Jestin; Warden, Craig; Colella, M. Riccardo; Brienza, Ashley; Aufderheide, Tom P.; Idris, Ahamed; Schmicker, Robert; May, Susanne; Nichol, Graham

2016-01-01

Airway management is an important component of resuscitation from out-of-hospital cardiac arrest (OHCA). The optimal approach to advanced airway management is unknown. The Pragmatic Airway Resuscitation Trial (PART) will compare the effectiveness of endotracheal intubation (ETI) and Laryngeal Tube (LT) insertion upon 72-hour survival in adult OHCA. Encompassing United States Emergency Medical Services agencies affiliated with the Resuscitation Outcomes Consortium (ROC), PART will use a cluster-crossover randomized design. Participating subjects will include adult, non-traumatic OHCA requiring bag-valve-mask ventilation. Trial interventions will include 1) initial airway management with ETI and 2) initial airway management with LT. The primary and secondary trial outcomes are 72-hour survival and return of spontaneous circulation. Additional clinical outcomes will include airway management process and adverse events. The trial will enroll a total of 3,000 subjects. Results of PART may guide the selection of advanced airway management strategies in OHCA. PMID:26851059

Microwave bale moisture sensing: Field trial

USDA-ARS?s Scientific Manuscript database

A microwave moisture measurement technique was developed for moisture sensing of cotton bales after the bale press. The technique measures the propagation delay of a microwave signal that is transmitted through the cotton bale. This research conducted a field trial to test the sensor in a commercial...

Linkages Among Agronomic, Environmental and Weed Management Characteristics in North American Sweet Corn

USDA-ARS?s Scientific Manuscript database

Performance of weed management systems varies greatly across the landscape in both growers’ fields and in experimental trials conducted by agricultural scientists. Using agronomic, environmental, and weed management information from growers’ fields and experimental trials, we identified dominant ch...

Field Trial of the Enhanced Data Authentication System (EDAS)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomas, Maikael A.; Baldwin, George T.; Hymel, Ross W.

2016-05-01

The goal of the field trial of EDAS was to demonstrate the utility of secure branching of operator instrumentation for nuclear safeguards, identify any unforeseen implementation and application issues with EDAS, and confirm whether the approach is compatible with operator concerns and constraints.

In silico modelling of drug–polymer interactions for pharmaceutical formulations

PubMed Central

Ahmad, Samina; Johnston, Blair F.; Mackay, Simon P.; Schatzlein, Andreas G.; Gellert, Paul; Sengupta, Durba; Uchegbu, Ijeoma F.

2010-01-01

Selecting polymers for drug encapsulation in pharmaceutical formulations is usually made after extensive trial and error experiments. To speed up excipient choice procedures, we have explored coarse-grained computer simulations (dissipative particle dynamics (DPD) and coarse-grained molecular dynamics using the MARTINI force field) of polymer–drug interactions to study the encapsulation of prednisolone (log p = 1.6), paracetamol (log p = 0.3) and isoniazid (log p = −1.1) in poly(l-lactic acid) (PLA) controlled release microspheres, as well as the encapsulation of propofol (log p = 4.1) in bioavailability enhancing quaternary ammonium palmitoyl glycol chitosan (GCPQ) micelles. Simulations have been compared with experimental data. DPD simulations, in good correlation with experimental data, correctly revealed that hydrophobic drugs (prednisolone and paracetamol) could be encapsulated within PLA microspheres and predicted the experimentally observed paracetamol encapsulation levels (5–8% of the initial drug level) in 50 mg ml−1 PLA microspheres, but only when initial paracetamol levels exceeded 5 mg ml−1. However, the mesoscale technique was unable to model the hydrophilic drug (isoniazid) encapsulation (4–9% of the initial drug level) which was observed in experiments. Molecular dynamics simulations using the MARTINI force field indicated that the self-assembly of GCPQ is rapid, with propofol residing at the interface between micellar hydrophobic and hydrophilic groups, and that there is a heterogeneous distribution of propofol within the GCPQ micelle population. GCPQ–propofol experiments also revealed a population of relatively empty and drug-filled GCPQ particles. PMID:20519214

Mating Disruption of Planococcus ficus (Hemiptera: Pseudococcidae) in Vineyards Using Reservoir Pheromone Dispensers

PubMed Central

Cocco, Arturo; Lentini, Andrea; Serra, Giuseppe

2014-01-01

Abstract Mating disruption field experiments to control the vine mealybug, Planococcus ficus (Signoret) (Hemiptera: Pseudococcidae), were carried out in 2008 and 2009 in two commercial vineyards in Sardinia (Italy). The effectiveness of mating disruption was evaluated by testing reservoir dispensers loaded with 100 mg (62.5 g/ha) and 150 mg (93.8 g/ha) of the sex pheromone in 2008 and 2009, respectively. The number of males captured in pheromone traps, the P. ficus population density and age structure, the parasitism rate, the percentage of ovipositing females, and the crop damage were compared between disrupted and untreated plots. In both field trials, the number of males captured in mating disruption plots was significantly reduced by 86% and 95%, respectively. Mating disruption at the initial dose of 62.5 g/ha of active ingredient gave inconclusive results, whereas the dose of 93.8 g/ha significantly lowered the mealybug density and modified the age structure, which showed a lower percentage of ovipositing females and a higher proportion of preovipositing females. Mating disruption did not affect negatively the parasitism rate, which was higher in the disrupted than in the control plots (>1.5-fold). Crop damage at harvest was very low in both field trials and did not differ between treatments. Mating disruption was effective in wide plots protected with dispensers loaded with 150 mg of the sex pheromone, showing its potential to be included in the overall integrated control programs in Mediterranean wine-growing regions. PMID:25347835

Barriers towards the publication of academic drug trials. Follow-up of trials approved by the Danish Medicines Agency.

PubMed

Berendt, Louise; Petersen, Lene Grejs; Bach, Karin Friis; Poulsen, Henrik Enghusen; Dalhoff, Kim

2017-01-01

To characterize and quantify barriers towards the publication of academic drug trials. We identified academic drug trials approved during a 3-year period (2004-2007) by the Danish Medicines Agency. We conducted a survey among the trial sponsors to describe the rates of initiation, completion, and publication, and the reasons for the failure to reach each of these milestones. Information on size and methodological characteristics of the trials was extracted from the EudraCT database, a prospective register of all approved clinical drug trials submitted to European medicines agencies since 2004. A total of 181 academic drug trials were eligible for inclusion, 139 of which participated in our survey (response rate: 77%). Follow-up time ranged from 5.1 to 7.9 years. Most trials were randomized controlled trials (73%, 95% CI 65-81%). Initiation and completion rates were 92% (95% CI: 88-97%) and 93% (95% CI: 89-97%) respectively. The publication rate of completed trials was 73% (95% CI: 62-79%). RCTs were published faster than non-RCTs (quartile time to publication 2.9 vs. 3.1 years, p = 0.0412). Many academic drug trials are left unpublished. Main barriers towards publication were related to the process from completion to publication. Hence, there is much to gain by facilitating the process from analysis to publication. Research institutions and funders should actively influence this process, e.g. by requiring the publication of trial results within a given time after completion.

The effects of a flexible visual acuity-driven ranibizumab treatment regimen in age-related macular degeneration: outcomes of a drug and disease model.

PubMed

Holz, Frank G; Korobelnik, Jean-François; Lanzetta, Paolo; Mitchell, Paul; Schmidt-Erfurth, Ursula; Wolf, Sebastian; Markabi, Sabri; Schmidli, Heinz; Weichselberger, Andreas

2010-01-01

Differences in treatment responses to ranibizumab injections observed within trials involving monthly (MARINA and ANCHOR studies) and quarterly (PIER study) treatment suggest that an individualized treatment regimen may be effective in neovascular age-related macular degeneration. In the present study, a drug and disease model was used to evaluate the impact of an individualized, flexible treatment regimen on disease progression. For visual acuity (VA), a model was developed on the 12-month data from ANCHOR, MARINA, and PIER. Data from untreated patients were used to model patient-specific disease progression in terms of VA loss. Data from treated patients from the period after the three initial injections were used to model the effect of predicted ranibizumab vitreous concentration on VA loss. The model was checked by comparing simulations of VA outcomes after monthly and quarterly injections during this period with trial data. A flexible VA-guided regimen (after the three initial injections) in which treatment is initiated by loss of >5 letters from best previously observed VA scores was simulated. Simulated monthly and quarterly VA-guided regimens showed good agreement with trial data. Simulation of VA-driven individualized treatment suggests that this regimen, on average, sustains the initial gains in VA seen in clinical trials at month 3. The model predicted that, on average, to maintain initial VA gains, an estimated 5.1 ranibizumab injections are needed during the 9 months after the three initial monthly injections, which amounts to a total of 8.1 injections during the first year. A flexible, individualized VA-guided regimen after the three initial injections may sustain vision improvement with ranibizumab and could improve cost-effectiveness and convenience and reduce drug administration-associated risks.

Timing at peak force may be the hidden target controlled in continuation and synchronization tapping.

PubMed

Du, Yue; Clark, Jane E; Whitall, Jill

2017-05-01

Timing control, such as producing movements at a given rate or synchronizing movements to an external event, has been studied through a finger-tapping task where timing is measured at the initial contact between finger and tapping surface or the point when a key is pressed. However, the point of peak force is after the time registered at the tapping surface and thus is a less obvious but still an important event during finger tapping. Here, we compared the time at initial contact with the time at peak force as participants tapped their finger on a force sensor at a given rate after the metronome was turned off (continuation task) or in synchrony with the metronome (sensorimotor synchronization task). We found that, in the continuation task, timing was comparably accurate between initial contact and peak force. These two timing events also exhibited similar trial-by-trial statistical dependence (i.e., lag-one autocorrelation). However, the central clock variability was lower at the peak force than the initial contact. In the synchronization task, timing control at peak force appeared to be less variable and more accurate than that at initial contact. In addition to lower central clock variability, the mean SE magnitude at peak force (SEP) was around zero while SE at initial contact (SEC) was negative. Although SEC and SEP demonstrated the same trial-by-trial statistical dependence, we found that participants adjusted the time of tapping to correct SEP, but not SEC, toward zero. These results suggest that timing at peak force is a meaningful target of timing control, particularly in synchronization tapping. This result may explain the fact that SE at initial contact is typically negative as widely observed in the preexisting literature.

Rats' Anticipation of Current and Future Trial Outcomes in the Ordered RNR/RNN Serial Pattern Task

ERIC Educational Resources Information Center

Cohen, Jerome; Mohamoud, Sirad; Szelest, Izabela; Kani, Tammy

2008-01-01

In the ordered RNR/RNN serial pattern task, rats often reduce their running speeds on trial 2 less within the RNR than within the RNN series. Initially, investigators (Capaldi, 1985; Capaldi et al., 1983) considered this trial 2 differential speed effect evidence for rats' anticipation of inter-trial outcomes within each series. Later findings,…

Reduction of radial-head subluxation in children by triage nurses in the emergency department: a cluster-randomized controlled trial

PubMed Central

Dixon, Andrew; Clarkin, Chantalle; Barrowman, Nick; Correll, Rhonda; Osmond, Martin H.; Plint, Amy C.

2014-01-01

Background: Radial-head subluxation is an easily identified and treated injury. We investigated whether triage nurses in the emergency department can safely reduce radial-head subluxation at rates that are not substantially lower than those of emergency department physicians. Methods: We performed an open, noninferiority, cluster-randomized control trial. Children aged 6 years and younger who presented to the emergency department with a presentation consistent with radial-head subluxation and who had sustained a known injury in the previous 12 hours were assigned to either nurse-initiated or physician-initiated treatment, depending on the day. The primary outcome was the proportion of children who had a successful reduction (return to normal arm usage). We used a noninferiority margin of 10%. Results: In total, 268 children were eligible for inclusion and 245 were included in the final analysis. Of the children assigned to receive physician-initiated care, 96.7% (117/121) had a successful reduction performed by a physician. Of the children assigned to receive nurse-treatment care, 84.7% (105/124) had a successful reduction performed by a nurse. The difference in the proportion of successful radial head subluxations between the groups was 12.0% (95% confidence interval [CI] 4.8% to 19.7%). Noninferiority of nurse-initiated radial head subluxation was not shown. Interpretation: In this trial, the rate of successful radial-head subluxation performed by nurses was inferior to the physician success rate. Although the success rate in the nurse-initiated care group did not meet the non-inferiority margin, nurses were able to reduce radial head subluxation for almost 85% of children who presented with probable radial-head subluxation. Trial registration: Clinical Trials.gov, no. NCT00993954. PMID:24664649

Contraceptive Use and Pregnancy Incidence Among Women Participating in an HIV Prevention Trial.

PubMed

Akello, Carolyne A; Bunge, Katherine E; Nakabiito, Clemensia; Mirembe, Brenda G; Fowler, Mary Glenn; Mishra, Anupam; Marrazzo, Jeanne; Chirenje, Zvavahera M; Celum, Connie; Balkus, Jennifer E

2017-06-01

Recent HIV prevention trials required use of effective contraceptive methods to fulfill eligibility for enrollment. We compared pregnancy rates in a subset of participants enrolled in the Microbicide Trials Network protocol (MTN-003), a randomized trial of chemoprophylaxis to prevent HIV acquisition among women aged 18-45 years who initiated depot medroxyprogesterone acetate (DMPA) or combined oral contraceptives (COCs) at enrollment, relative to those already using DMPA or COCs. Data were analyzed from MTN-003 participants from Uganda. Before enrollment, information on contraceptive type and initiation date was obtained. Urine pregnancy tests were performed at monthly follow-up visits. Cox proportional hazards models were used to compare pregnancy incidence among new users (initiated ≤60 days before enrollment) and established users (initiated >60 days before enrollment). Of 322 women enrolled, 296 were COC or DMPA users, 82 (28%) were new users, and 214 (72%) were established users. Pregnancy incidence was higher among new contraceptive users compared to established users (20.70% vs. 10.55%; adjusted hazard ratio [HR] = 1.66; 95% confidence interval [95% CI] 0.93-2.96). Among DMPA users, pregnancy incidence was 10.20% in new users versus 3.48% in established users (HR = 2.56; 95% CI 0.86-7.65). Among new COC users, pregnancy incidence was 42.67% in new users versus 23.67% in established COC users (adjusted HR = 1.74; 95% CI 0.87-3.48). New contraceptive users, regardless of method, at the Uganda MTN-003 site had an increased pregnancy risk compared to established users, which may be due to contraceptive initiation primarily for trial eligibility. New users may benefit from intensive contraceptive counseling and additional contraceptive options, including longer acting reversible contraceptives.

A comparison of the clinical field efficacy and safety of florfenicol and tilmicosin for the treatment of undifferentiated bovine respiratory disease of cattle in western Canada.

PubMed Central

Hoar, B R; Jelinski, M D; Ribble, C S; Janzen, E D; Johnson, J C

1998-01-01

We compared the field efficacy of a new antibiotic, florfenicol, with tilmicosin in the treatment of naturally occurring undifferentiated bovine respiratory disease. Beef calves with rectal temperatures greater than 40.5 degrees C and signs compatible with undifferentiated bovine respiratory disease were entered into the trial. Calves were randomly assigned to receive either florfenicol (20 mg/kg bodyweight intramuscularly; 2 injections 48 h apart) or tilmicosin (10 mg/kg bodyweight subcutaneously; 1 injection). Clinical measures of efficacy included mortality, rectal temperature, illness index score, assessment of treatment success or failure, and the number of relapses or reinfections. Performance was assessed based on weight gains from day 0 to day 90. Two hundred and twenty calves entered the trial; 112 received florfenicol and 108 received tilmicosin. Seventeen deaths occurred between day 0 and day 90, but only 10 during the 28-day trial period. Seven calves receiving tilmicosin died, compared with 3 receiving florfenicol (P = 0.20). Of the 220 initial treatments, 45 (20%) were categorized as treatment failures; 27 in the tilmicosin group and 18 in the florfenicol group (P = 0.10). The number of calves experiencing a 2nd relapse was significantly different, with 17 of 30 (57%) calves on tilmicosin compared with 7 of 26 (27%) calves on florfenicol relapsing at least twice (P = 0.02). Average daily gains over 90 days were 1.55 kg/day for florfenicol-treated calves and 1.51 kg/day for tilmicosin-treated calves. No significant adverse reactions were noticed with either drug. Results indicate that florfenicol and tilmicosin are comparable in the treatment of undifferentiated bovine respiratory disease in western Canada. Images Figure 2. Figure 3. PMID:9524721

Influence of newborn health messages on care-seeking practices and community health behaviors among participants in the Zambia Chlorhexidine Application Trial.

PubMed

Sivalogan, Kasthuri; Semrau, Katherine E A; Ashigbie, Paul G; Mwangi, Sheila; Herlihy, Julie M; Yeboah-Antwi, Kojo; Banda, Bowen; Grogan, Caroline; Biemba, Godfrey; Hamer, Davidson H

2018-01-01

Identifying and understanding traditional perceptions that influence newborn care practices and care-seeking behavior are crucial to developing sustainable interventions to improve neonatal health. The Zambia Chlorhexidine Application Trial (ZamCAT), a large-scale cluster randomized trial, assessed the impact of 4% chlorhexidine on neonatal mortality and omphalitis in Southern Province, Zambia. The main purpose of this post-ZamCAT qualitative study was to understand the impact of newborn care health messages on care-seeking behavior for neonates and the acceptability, knowledge, and attitudes towards chlorhexidine cord care among community members and health workers in Southern Province. Five focus group discussions and twenty-six in-depth interviews were conducted with mothers and health workers from ten health centers (5 rural and 5 peri-urban/urban). Community perceptions and local realities were identified as fundamental to care-seeking decisions and influenced individual participation in particular health-seeking behaviors. ZamCAT field monitors (data collectors) disseminated health messages at the time of recruitment at the health center and during subsequent home visits. Mothers noted that ZamCAT field monitors were effective in providing lessons and education on newborn care practices and participating mothers were able to share these messages with others in their communities. Although the study found no effect of chlorhexidine cord washes on neonatal mortality, community members had positive views towards chlorhexidine as they perceived that it reduced umbilical cord infections and was a beneficial alternative to traditional cord applications. The acceptability of health initiatives, such as chlorhexidine cord application, in community settings, is dependent on community education, understanding, and engagement. Community-based approaches, such as using community-based cadres of health workers to strengthen referrals, are an acceptable and potentially effective strategy to improve care-seeking behaviors and practices.

Delay activity of saccade-related neurons in the caudal dentate nucleus of the macaque cerebellum

PubMed Central

Sommer, Marc A.

2013-01-01

The caudal dentate nucleus (DN) in lateral cerebellum is connected with two visual/oculomotor areas of the cerebrum: the frontal eye field and lateral intraparietal cortex. Many neurons in frontal eye field and lateral intraparietal cortex produce “delay activity” between stimulus and response that correlates with processes such as motor planning. Our hypothesis was that caudal DN neurons would have prominent delay activity as well. From lesion studies, we predicted that this activity would be related to self-timing, i.e., the triggering of saccades based on the internal monitoring of time. We recorded from neurons in the caudal DN of monkeys (Macaca mulatta) that made delayed saccades with or without a self-timing requirement. Most (84%) of the caudal DN neurons had delay activity. These neurons conveyed at least three types of information. First, their activity was often correlated, trial by trial, with saccade initiation. Correlations were found more frequently in a task that required self-timing of saccades (53% of neurons) than in a task that did not (27% of neurons). Second, the delay activity was often tuned for saccade direction (in 65% of neurons). This tuning emerged continuously during a trial. Third, the time course of delay activity associated with self-timed saccades differed significantly from that associated with visually guided saccades (in 71% of neurons). A minority of neurons had sensory-related activity. None had presaccadic bursts, in contrast to DN neurons recorded more rostrally. We conclude that caudal DN neurons convey saccade-related delay activity that may contribute to the motor preparation of when and where to move. PMID:23365182

Effect of Risk of Bias on the Effect Size of Meta-Analytic Estimates in Randomized Controlled Trials in Periodontology and Implant Dentistry

PubMed Central

Faggion, Clovis Mariano; Wu, Yun-Chun; Scheidgen, Moritz; Tu, Yu-Kang

2015-01-01

Background Risk of bias (ROB) may threaten the internal validity of a clinical trial by distorting the magnitude of treatment effect estimates, although some conflicting information on this assumption exists. Objective The objective of this study was evaluate the effect of ROB on the magnitude of treatment effect estimates in randomized controlled trials (RCTs) in periodontology and implant dentistry. Methods A search for Cochrane systematic reviews (SRs), including meta-analyses of RCTs published in periodontology and implant dentistry fields, was performed in the Cochrane Library in September 2014. Random-effect meta-analyses were performed by grouping RCTs with different levels of ROBs in three domains (sequence generation, allocation concealment, and blinding of outcome assessment). To increase power and precision, only SRs with meta-analyses including at least 10 RCTs were included. Meta-regression was performed to investigate the association between ROB characteristics and the magnitudes of intervention effects in the meta-analyses. Results Of the 24 initially screened SRs, 21 SRs were excluded because they did not include at least 10 RCTs in the meta-analyses. Three SRs (two from periodontology field) generated information for conducting 27 meta-analyses. Meta-regression did not reveal significant differences in the relationship of the ROB level with the size of treatment effect estimates, although a trend for inflated estimates was observed in domains with unclear ROBs. Conclusion In this sample of RCTs, high and (mainly) unclear risks of selection and detection biases did not seem to influence the size of treatment effect estimates, although several confounders might have influenced the strength of the association. PMID:26422698

Ghosts in the Machine II: Neural Correlates of Memory Interference from the Previous Trial.

PubMed

Papadimitriou, Charalampos; White, Robert L; Snyder, Lawrence H

2017-04-01

Previous memoranda interfere with working memory. For example, spatial memories are biased toward locations memorized on the previous trial. We predicted, based on attractor network models of memory, that activity in the frontal eye fields (FEFs) encoding a previous target location can persist into the subsequent trial and that this ghost will then bias the readout of the current target. Contrary to this prediction, we find that FEF memory representations appear biased away from (not toward) the previous target location. The behavioral and neural data can be reconciled by a model in which receptive fields of memory neurons converge toward remembered locations, much as receptive fields converge toward attended locations. Convergence increases the resources available to encode the relevant memoranda and decreases overall error in the network, but the residual convergence from the previous trial can give rise to an attractive behavioral bias on the next trial. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Auxiliary-field-based trial wave functions in quantum Monte Carlo calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, Chia -Chen; Rubenstein, Brenda M.; Morales, Miguel A.

2016-12-19

Quantum Monte Carlo (QMC) algorithms have long relied on Jastrow factors to incorporate dynamic correlation into trial wave functions. While Jastrow-type wave functions have been widely employed in real-space algorithms, they have seen limited use in second-quantized QMC methods, particularly in projection methods that involve a stochastic evolution of the wave function in imaginary time. Here we propose a scheme for generating Jastrow-type correlated trial wave functions for auxiliary-field QMC methods. The method is based on decoupling the two-body Jastrow into one-body projectors coupled to auxiliary fields, which then operate on a single determinant to produce a multideterminant trial wavemore » function. We demonstrate that intelligent sampling of the most significant determinants in this expansion can produce compact trial wave functions that reduce errors in the calculated energies. Lastly, our technique may be readily generalized to accommodate a wide range of two-body Jastrow factors and applied to a variety of model and chemical systems.« less

Biochar: from laboratory mechanisms through the greenhouse to field trials

NASA Astrophysics Data System (ADS)

Masiello, C. A.; Gao, X.; Dugan, B.; Silberg, J. J.; Zygourakis, K.; Alvarez, P. J. J.

2014-12-01

The biochar community is excellent at pointing to individual cases where biochar amendment has changed soil properties, with some studies showing significant improvements in crop yields, reduction in nutrient export, and remediation of pollutants. However, many studies exist which do not show improvements, and in some cases, studies clearly show detrimental outcomes. The next, crucial step in biochar science and engineering research will be to develop a process-based understanding of how biochar acts to improve soil properties. In particular, we need a better mechanistic understanding of how biochar sorbs and desorbs contaminants, how it interacts with soil water, and how it interacts with the soil microbial community. These mechanistic studies need to encompass processes that range from the nanometer to the kilometer scale. At the nanometer scale, we need a predictive model of how biochar will sorb and desorb hydrocarbons, nutrients, and toxic metals. At the micrometer scale we need models that explain biochar's effects on soil water, especially the plant-available fraction of soil water. The micrometer scale is also where mechanistic information is neeed about microbial processes. At the macroscale we need physical models to describe the landscape mobility of biochar, because biochar that washes away from fields can no longer provide crop benefits. To be most informative, biochar research should occur along a lab-greenhouse-field trial trajectory. Laboratory experiments should aim determine what mechanisms may act to control biochar-soil processes, and then greenhouse experiments can be used to test the significance of lab-derived mechanisms in short, highly replicated, controlled experiments. Once evidence of effect is determined from greenhouse experiments, field trials are merited. Field trials are the gold standard needed prior to full deployment, but results from field trials cannot be extrapolated to other field sites without the mechanistic backup provided by greenhouse and lab trials.

7 CFR 1755.3 - Field trials.

Code of Federal Regulations, 2010 CFR

2010-01-01

... system electronics; (vi) Fiber optic cable system electronics; (vii) Multiplex equipment; (viii) Mobile... Telephone Systems of RUS Borrowers,” RUS Bulletin 344-2. When new items of materials or equipment are... that the field trial is carried out and that the required information on the product's performance is...

Evolution of the magnetorotational instability on initially tangled magnetic fields

NASA Astrophysics Data System (ADS)

Bhat, Pallavi; Ebrahimi, Fatima; Blackman, Eric G.; Subramanian, Kandaswamy

2017-12-01

The initial magnetic field of previous magnetorotational instability (MRI) simulations has always included a significant system-scale component, even if stochastic. However, it is of conceptual and practical interest to assess whether the MRI can grow when the initial field is turbulent. The ubiquitous presence of turbulent or random flows in astrophysical plasmas generically leads to a small-scale dynamo (SSD), which would provide initial seed turbulent velocity and magnetic fields in the plasma that becomes an accretion disc. Can the MRI grow from these more realistic initial conditions? To address this, we supply a standard shearing box with isotropically forced SSD generated magnetic and velocity fields as initial conditions and remove the forcing. We find that if the initially supplied fields are too weak or too incoherent, they decay from the initial turbulent cascade faster than they can grow via the MRI. When the initially supplied fields are sufficient to allow MRI growth and sustenance, the saturated stresses, large-scale fields and power spectra match those of the standard zero net flux MRI simulation with an initial large-scale vertical field.

The burden of proof: The current state of atrial fibrillation prevention and treatment trials

PubMed Central

Zakeri, Rosita; Van Wagoner, David R.; Calkins, Hugh; Wong, Tom; Ross, Heather M.; Heist, E. Kevin; Meyer, Timothy E.; Kowey, Peter R.; Mentz, Robert J.; Cleland, John G.; Pitt, Bertram; Zannad, Faiez; Linde, Cecilia

2017-01-01

Atrial fibrillation (AF) is an age-related arrhythmia of enormous socioeconomic significance. In recent years, our understanding of the basic mechanisms that initiate and perpetuate AF has evolved rapidly, catheter ablation of AF has progressed from concept to reality, and recent studies suggest lifestyle modification may help prevent AF recurrence. Emerging developments in genetics, imaging, and informatics also present new opportunities for personalized care. However, considerable challenges remain. These include a paucity of studies examining AF prevention, modest efficacy of existing antiarrhythmic therapies, diverse ablation technologies and practice, and limited evidence to guide management of high-risk patients with multiple comorbidities. Studies examining the long-term effects of AF catheter ablation on morbidity and mortality outcomes are not yet completed. In many ways, further progress in the field is heavily contingent on the feasibility, capacity, and efficiency of clinical trials to incorporate the rapidly evolving knowledge base and to provide substantive evidence for novel AF therapeutic strategies. This review outlines the current state of AF prevention and treatment trials, including the foreseeable challenges, as discussed by a unique forum of clinical trialists, scientists, and regulatory representatives in a session endorsed by the Heart Rhythm Society at the 12th Global CardioVascular Clinical Trialists Forum in Washington, DC, December 3–5, 2015. PMID:28161513

Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial

PubMed Central

Coghlan, John Gerry; Galiè, Nazzareno; Barberà, Joan Albert; Frost, Adaani E; Ghofrani, Hossein-Ardeschir; Hoeper, Marius M; Kuwana, Masataka; McLaughlin, Vallerie V; Peacock, Andrew J; Simonneau, Gérald; Vachiéry, Jean-Luc; Blair, Christiana; Gillies, Hunter; Miller, Karen L; Harris, Julia H N; Langley, Jonathan; Rubin, Lewis J

2017-01-01

Background Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), in particular systemic sclerosis (SSc), had an attenuated response compared with idiopathic PAH in most trials. Thus, there is uncertainty regarding the benefit of PAH-targeted therapy in some forms of CTD-PAH. Objective To explore the safety and efficacy of initial combination therapy with ambrisentan and tadalafil versus ambrisentan or tadalafil monotherapy in patients with CTD-PAH and SSc-PAH enrolled in the AMBITION trial. Methods This was a post hoc analysis of patients with CTD-PAH and SSc-PAH from AMBITION, an event-driven, double-blind trial in patients with WHO functional class II/III PAH. Treatment-naive patients were randomised 2:1:1 to once-daily initial combination therapy with ambrisentan plus tadalafil or monotherapy with ambrisentan or tadalafil, respectively. The primary endpoint was time to the first clinical failure event (first occurrence of death, hospitalisation for worsening PAH, disease progression or unsatisfactory long-term clinical response). Results In the primary analysis set (N=500), 187 patients had CTD-PAH, of whom 118 had SSc-PAH. Initial combination therapy reduced the risk of clinical failure versus pooled monotherapy in each subgroup: CTD-PAH (HR 0.43 (95% CI 0.24 to 0.77)) and SSc-PAH (0.44 (0.22 to 0.89)). The most common AE was peripheral oedema, which was reported more frequently with initial combination therapy than monotherapy in the two PAH subgroups. The relative frequency of adverse events between those on combination therapy versus monotherapy was similar across subgroups. Conclusions This post hoc subgroup analysis provides evidence that CTD-PAH and SSc-PAH patients benefit from initial ambrisentan and tadalafil combination therapy. Trial registration number NCT01178073, post results. PMID:28039187

A split band-Cholesky equation solving strategy for finite element analysis of transient field problems. [in fluid mechanics

NASA Technical Reports Server (NTRS)

Cooke, C. H.

1978-01-01

The paper describes the split-Cholesky strategy for banded matrices arising from the large systems of equations in certain fluid mechanics problems. The basic idea is that for a banded matrix the computation can be carried out in pieces, with only a small portion of the matrix residing in core. Mesh considerations are discussed by demonstrating the manner in which the assembly of finite element equations proceeds for linear trial functions on a triangular mesh. The FORTRAN code which implements the out-of-core decomposition strategy for banded symmetric positive definite matrices (mass matrices) of a coupled initial value problem is given.

Extended Wearing Trial of Trifield Lens Device for “Tunnel Vision”

PubMed Central

Woods, Russell L.; Giorgi, Robert G.; Berson, Eliot L.; Peli, Eli

2009-01-01

Severe visual field constriction (tunnel vision) impairs the ability to navigate and walk safely. We evaluated Trifield glasses as a mobility rehabilitation device for tunnel vision in an extended wearing trial. Twelve patients with tunnel vision (5 to 22 degrees wide) due to retinitis pigmentosa or choroideremia participated in the 5-visit wearing trial. To expand the horizontal visual field, one spectacle lens was fitted with two apex-to-apex prisms that vertically bisected the pupil on primary gaze. This provides visual field expansion at the expense of visual confusion (two objects with the same visual direction). Patients were asked to wear these spectacles as much as possible for the duration of the wearing trial (median 8, range 6 to 60, weeks). Clinical success (continued wear, indicating perceived overall benefit), visual field expansion, perceived direction and perceived visual ability were measured. Of 12 patients, 9 chose to continue wearing the Trifield glasses at the end of the wearing trial. Of those 9 patients, at long-term follow-up (35 to 78 weeks), 3 reported still wearing the Trifield glasses. Visual field expansion (median 18, range 9 to 38, degrees) was demonstrated for all patients. No patient demonstrated adaptation to the change in visual direction produced by the Trifield glasses (prisms). For difficulty with obstacles, some differences between successful and non-successful wearers were found. Trifield glasses provided reported benefits in obstacle avoidance to 7 of the 12 patients completing the wearing trial. Crowded environments were particularly difficult for most wearers. Possible reasons for long-term discontinuation and lack of adaptation to perceived direction are discussed. PMID:20444130

Extended wearing trial of Trifield lens device for 'tunnel vision'.

PubMed

Woods, Russell L; Giorgi, Robert G; Berson, Eliot L; Peli, Eli

2010-05-01

Severe visual field constriction (tunnel vision) impairs the ability to navigate and walk safely. We evaluated Trifield glasses as a mobility rehabilitation device for tunnel vision in an extended wearing trial. Twelve patients with tunnel vision (5-22 degrees wide) due to retinitis pigmentosa or choroideremia participated in the 5-visit wearing trial. To expand the horizontal visual field, one spectacle lens was fitted with two apex-to-apex prisms that vertically bisected the pupil on primary gaze. This provides visual field expansion at the expense of visual confusion (two objects with the same visual direction). Patients were asked to wear these spectacles as much as possible for the duration of the wearing trial (median 8, range 6-60 weeks). Clinical success (continued wear, indicating perceived overall benefit), visual field expansion, perceived direction and perceived visual ability were measured. Of 12 patients, nine chose to continue wearing the Trifield glasses at the end of the wearing trial. Of those nine patients, at long-term follow-up (35-78 weeks), three reported still wearing the Trifield glasses. Visual field expansion (median 18, range 9-38 degrees) was demonstrated for all patients. No patient demonstrated adaptation to the change in visual direction produced by the Trifield glasses (prisms). For reported difficulty with obstacles, some differences between successful and non-successful wearers were found. Trifield glasses provided reported benefits in obstacle avoidance to 7 of the 12 patients completing the wearing trial. Crowded environments were particularly difficult for most wearers. Possible reasons for long-term discontinuation and lack of adaptation to perceived direction are discussed.

Estimating economic thresholds for site-specific weed control using manual weed counts and sensor technology: an example based on three winter wheat trials.

PubMed

Keller, Martina; Gutjahr, Christoph; Möhring, Jens; Weis, Martin; Sökefeld, Markus; Gerhards, Roland

2014-02-01

Precision experimental design uses the natural heterogeneity of agricultural fields and combines sensor technology with linear mixed models to estimate the effect of weeds, soil properties and herbicide on yield. These estimates can be used to derive economic thresholds. Three field trials are presented using the precision experimental design in winter wheat. Weed densities were determined by manual sampling and bi-spectral cameras, yield and soil properties were mapped. Galium aparine, other broad-leaved weeds and Alopecurus myosuroides reduced yield by 17.5, 1.2 and 12.4 kg ha(-1) plant(-1)  m(2) in one trial. The determined thresholds for site-specific weed control with independently applied herbicides were 4, 48 and 12 plants m(-2), respectively. Spring drought reduced yield effects of weeds considerably in one trial, since water became yield limiting. A negative herbicide effect on the crop was negligible, except in one trial, in which the herbicide mixture tended to reduce yield by 0.6 t ha(-1). Bi-spectral cameras for weed counting were of limited use and still need improvement. Nevertheless, large weed patches were correctly identified. The current paper presents a new approach to conducting field trials and deriving decision rules for weed control in farmers' fields. © 2013 Society of Chemical Industry.

Clinical trial designs for rare diseases: Studies developed and discussed by the International Rare Cancers Initiative

PubMed Central

Bogaerts, Jan; Sydes, Matthew R.; Keat, Nicola; McConnell, Andrea; Benson, Al; Ho, Alan; Roth, Arnaud; Fortpied, Catherine; Eng, Cathy; Peckitt, Clare; Coens, Corneel; Pettaway, Curtis; Arnold, Dirk; Hall, Emma; Marshall, Ernie; Sclafani, Francesco; Hatcher, Helen; Earl, Helena; Ray-Coquard, Isabelle; Paul, James; Blay, Jean-Yves; Whelan, Jeremy; Panageas, Kathy; Wheatley, Keith; Harrington, Kevin; Licitra, Lisa; Billingham, Lucinda; Hensley, Martee; McCabe, Martin; Patel, Poulam M.; Carvajal, Richard; Wilson, Richard; Glynne-Jones, Rob; McWilliams, Rob; Leyvraz, Serge; Rao, Sheela; Nicholson, Steve; Filiaci, Virginia; Negrouk, Anastassia; Lacombe, Denis; Dupont, Elisabeth; Pauporté, Iris; Welch, John J.; Law, Kate; Trimble, Ted; Seymour, Matthew

2015-01-01

Background The past three decades have seen rapid improvements in the diagnosis and treatment of most cancers and the most important contributor has been research. Progress in rare cancers has been slower, not least because of the challenges of undertaking research. Settings The International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. It is focused on interventional – usually randomised – clinical trials with the clear goal of improving outcomes for patients. The key challenges are organisational and methodological. A multi-disciplinary workshop to review the methods used in ICRI portfolio trials was held in Amsterdam in September 2013. Other as-yet unrealised methods were also discussed. Results The IRCI trials are each presented to exemplify possible approaches to designing credible trials in rare cancers. Researchers may consider these for use in future trials and understand the choices made for each design. Interpretation Trials can be designed using a wide array of possibilities. There is no ‘one size fits all’ solution. In order to make progress in the rare diseases, decisions to change practice will have to be based on less direct evidence from clinical trials than in more common diseases. PMID:25542058

DESIGNING PHASE 0 CANCER CLINICAL TRIALS

PubMed Central

Murgo, Anthony J.; Kummar, Shivaani; Rubinstein, Larry; Gutierrez, Martin; Collins, Jerry; Kinders, Robert; Parchment, Ralph E.; Ji, Jiuping; Steinberg, Seth M.; Yang, Sherry X.; Hollingshead, Melinda; Chen, Alice; Helman, Lee; Wiltrout, Robert; Tomaszewski, Joseph E.; Doroshow, James H.

2008-01-01

Phase 0 trials are designed primarily to evaluate the pharmacodynamic and/or pharmacokinetic properties of selected investigational agents prior to initiating more traditional phase 1 testing. One of the major objectives of phase 0 trials is to interrogate and refine a target or biomarker assay for drug effect in human samples implementing procedures developed and validated in preclinical models. Thus, close collaboration between laboratory scientists and clinical investigators is essential to the design and conduct of phase 0 trials. Given the relatively small number of patients and tissue samples, demonstrating a significant drug effect in phase 0 trials requires precise and reproducible assay procedures and innovative statistical methodology. Furthermore, phase 0 trials involving limited exposure of study agent administered at low doses and/or for a short period allows them to be initiated under the FDA Exploratory IND Guidance with less preclinical toxicity data than usually required for traditional first-in-human studies. Because of the very limited drug exposure, phase 0 trials offer no chance of therapeutic benefit, which can impede patient enrollment, particularly if invasive tumor biopsies are required. However, the challenges to accrual are not insurmountable, and well-designed and executed phase 0 trials are feasible and have great potential for improving the efficiency and success of subsequent trials, particularly those evaluating molecularly targeted agents. PMID:18559582

Clinical trial designs for rare diseases: studies developed and discussed by the International Rare Cancers Initiative.

PubMed

Bogaerts, Jan; Sydes, Matthew R; Keat, Nicola; McConnell, Andrea; Benson, Al; Ho, Alan; Roth, Arnaud; Fortpied, Catherine; Eng, Cathy; Peckitt, Clare; Coens, Corneel; Pettaway, Curtis; Arnold, Dirk; Hall, Emma; Marshall, Ernie; Sclafani, Francesco; Hatcher, Helen; Earl, Helena; Ray-Coquard, Isabelle; Paul, James; Blay, Jean-Yves; Whelan, Jeremy; Panageas, Kathy; Wheatley, Keith; Harrington, Kevin; Licitra, Lisa; Billingham, Lucinda; Hensley, Martee; McCabe, Martin; Patel, Poulam M; Carvajal, Richard; Wilson, Richard; Glynne-Jones, Rob; McWilliams, Rob; Leyvraz, Serge; Rao, Sheela; Nicholson, Steve; Filiaci, Virginia; Negrouk, Anastassia; Lacombe, Denis; Dupont, Elisabeth; Pauporté, Iris; Welch, John J; Law, Kate; Trimble, Ted; Seymour, Matthew

2015-02-01

The past three decades have seen rapid improvements in the diagnosis and treatment of most cancers and the most important contributor has been research. Progress in rare cancers has been slower, not least because of the challenges of undertaking research. The International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. It is focused on interventional--usually randomized--clinical trials with the clear goal of improving outcomes for patients. The key challenges are organisational and methodological. A multi-disciplinary workshop to review the methods used in ICRI portfolio trials was held in Amsterdam in September 2013. Other as-yet unrealised methods were also discussed. The IRCI trials are each presented to exemplify possible approaches to designing credible trials in rare cancers. Researchers may consider these for use in future trials and understand the choices made for each design. Trials can be designed using a wide array of possibilities. There is no 'one size fits all' solution. In order to make progress in the rare diseases, decisions to change practice will have to be based on less direct evidence from clinical trials than in more common diseases. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

In Vitro Cryopreservation of Date Palm Caulogenic Meristems.

PubMed

Fki, Lotfi; Chkir, Olfa; Kriaa, Walid; Nasri, Ameni; Baklouti, Emna; Masmoudi, Raja B; Rival, Alain; Drira, Noureddine; Panis, Bart

2017-01-01

Cryopreservation is the technology of choice not only for plant genetic resource preservation but also for virus eradication and for the efficient management of large-scale micropropagation. In this chapter, we describe three cryopreservation protocols (standard vitrification, droplet vitrification, and encapsulation vitrification) for date palm highly proliferating meristems that are initiated from vitro-cultures using plant growth regulator-free MS medium. The positive impact of sucrose preculture and cold hardening treatments on survival rates is significant. Regeneration rates obtained with standard vitrification, encapsulation-vitrification, and droplet-vitrification protocols can reach 30, 40, and 70%, respectively. All regenerated plants from non-cryopreserved or cryopreserved explants don't show morphological variation by maintaining genetic integrity without adverse effect of cryogenic treatment. Cryopreservation of date palm vitro-cultures enables commercial tissue culture laboratories to move to large-scale propagation from cryopreserved cell lines producing true-to-type plants after clonal field-testing trials. When comparing the cost of cryostorage and in-field conservation of date palm cultivars, tissue cryopreservation is the most cost-effective. Moreover, many of the risks linked to field conservation like erosion due to climatic, edaphic, and phytopathologic constraints are circumvented.

UV Waterworks Outreach Support. Final Report

DOE R&D Accomplishments Database

Miller, P.

1998-05-01

A recently invented device uses UV light (254 nm) to inexpensively disinfect community drinking water supplies. Its novel features are: low cost (about US $600), robust design, rapid disinfection (12 seconds), low electricity use (40W), low maintenance (every 6 months), high flow rate (15 l/min) and ability to work with unpressurized water sources. The device could service a community of 1,000 persons, at an annual total cost of 14 cents US per person. This device has been tested in a number of independent laboratories worldwide. The laboratory tests have confirmed that the unit is capable of disinfecting waters to drinking water standards for bacteria and viruses. An extended field trial of the device began in South Africa in February 1997, with lab testing at the municipal water utility. A unit installed at the first field site, an AIDS hospice near Durban, has been in continuous operation since August, 1997. Additional test sites are being identified. The author describes the results of the initial lab tests, reports the most recent findings from the ongoing field test-monitoring program, and discusses plans for future tests.

Citation measures in stereotactic radiosurgery: publication across a discipline.

PubMed

Kondziolka, Douglas

2011-01-01

It is possible to judge the impact of scientific research by the number of citations a publication has received. We identified the most cited works in the field of stereotactic radiosurgery to study the evolution of this field from the perspective of publication. A Web of Science search was performed for articles that included the word 'radiosurgery' in the title. We studied the reports with >100 citations. A total of 5,532 published works were available for study between 1951 and 2010. Eighty-five articles had ≥ 100 citations, and these were published in 19 separate journals. The majority were published in the International Journal of Radiation Oncology, Biology and Physics, the Journal of Neurosurgery and Neurosurgery. The most common topics included brain metastasis management (n = 20), arteriovenous malformations (n = 17), vestibular schwannomas (n = 9), technologies (n = 9), meningiomas (n = 8) and dose response/radiobiology (n = 6). Fifty-seven percent of the articles were published in the last 10 years. The first radiosurgery report by Leksell (1951) initiated the field. The 1980s were a period of new technology development followed in the 1990s by introductory articles on specific indications that consisted mainly of retrospective case series. More sophisticated higher level evidence reports were published in the last decade. The most significant works in radiosurgery include initial technology descriptions, multicenter studies with large numbers of patients, randomized clinical trials and reports that provide dose prescription guidelines. Copyright © 2011 S. Karger AG, Basel.

Eye Movements Reveal Fast, Voice-Specific Priming

PubMed Central

Papesh, Megan H.; Goldinger, Stephen D.; Hout, Michael C.

2015-01-01

In spoken word perception, voice specificity effects are well-documented: When people hear repeated words in some task, performance is generally better when repeated items are presented in their originally heard voices, relative to changed voices. A key theoretical question about voice specificity effects concerns their time-course: Some studies suggest that episodic traces exert their influence late in lexical processing (the time-course hypothesis; McLennan & Luce, 2005), whereas others suggest that episodic traces influence immediate, online processing. We report two eye-tracking studies investigating the time-course of voice-specific priming within and across cognitive tasks. In Experiment 1, participants performed modified lexical decision or semantic classification to words spoken by four speakers. The tasks required participants to click a red “×” or a blue “+” located randomly within separate visual half-fields, necessitating trial-by-trial visual search with consistent half-field response mapping. After a break, participants completed a second block with new and repeated items, half spoken in changed voices. Voice effects were robust very early, appearing in saccade initiation times. Experiment 2 replicated this pattern while changing tasks across blocks, ruling out a response priming account. In the General Discussion, we address the time-course hypothesis, focusing on the challenge it presents for empirical disconfirmation, and highlighting the broad importance of indexical effects, beyond studies of priming. PMID:26726911

Impact of individual clinical outcomes on trial participants' perspectives on enrollment in emergency research without consent.

PubMed

Whitesides, Louisa W; Baren, Jill M; Biros, Michelle H; Fleischman, Ross J; Govindarajan, Prasanthi R; Jones, Elizabeth B; Pancioli, Arthur M; Pentz, Rebecca D; Scicluna, Victoria M; Wright, David W; Dickert, Neal W

2017-04-01

Evidence suggests that patients are generally accepting of their enrollment in trials for emergency care conducted under exception from informed consent. It is unknown whether individuals with more severe initial injuries or worse clinical outcomes have different perspectives. Determining whether these differences exist may help to structure post-enrollment interactions. Primary clinical data from the Progesterone for the Treatment of Traumatic Brain Injury trial were matched to interview data from the Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study. Answers to three key questions from Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study were analyzed in the context of enrolled patients' initial injury severity (initial Glasgow Coma Scale and Injury Severity Score) and principal clinical outcomes (Extended Glasgow Outcome Scale and Extended Glasgow Outcome Scale relative to initial injury severity). The three key questions from Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study addressed participants' general attitude toward inclusion in the Progesterone for the Treatment of Traumatic Brain Injury trial (general trial inclusion), their specific attitude toward being included in Progesterone for the Treatment of Traumatic Brain Injury trial under the exception from informed consent (personal exception from informed consent enrollment), and their attitude toward the use of exception from informed consent in the Progesterone for the Treatment of Traumatic Brain Injury trial in general (general exception from informed consent enrollment). Qualitative analysis of interview transcripts was performed to provide contextualization and to determine the extent to which respondents framed their attitudes in terms of clinical experience. Clinical data from Progesterone for the Treatment of Traumatic Brain Injury trial were available for all 74 patients represented in the Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study (including 46 patients for whom the surrogate was interviewed due to the patient's cognitive status or death). No significant difference was observed regarding acceptance of general trial inclusion or acceptance of general exception from informed consent enrollment between participants with favorable neurological outcomes and those with unfavorable outcomes relative to initial injury. Agreement with personal enrollment in Progesterone for the Treatment of Traumatic Brain Injury trial under exception from informed consent, however, was significantly higher among participants with favorable outcomes compared to those with unfavorable outcomes (89% vs 59%, p = 0.003). There was also a statistically significant relationship between more severe initial injury and increased acceptance of personal exception from informed consent enrollment ( p = 0.040) or general exception from informed consent use ( p = 0.034) in Progesterone for the Treatment of Traumatic Brain Injury trial. Many individuals referenced personal experience as a basis for their attitudes, but these references were not used to support negative views. Patients and surrogates of patients with unfavorable clinical outcomes were somewhat less accepting of their own inclusion in the Progesterone for the Treatment of Traumatic Brain Injury trial under exception from informed consent than were patients or surrogates of patients with favorable clinical outcomes. These findings suggest a need to identify optimal strategies for communicating with patients and their surrogates regarding exception from informed consent enrollment when clinical outcomes are poor.

Immediate effect of couple relationship education on low-satisfaction couples: a randomized clinical trial plus an uncontrolled trial replication.

PubMed

Kim Halford, W; Pepping, Christopher A; Hilpert, Peter; Bodenmann, Guy; Wilson, Keithia L; Busby, Dean; Larson, Jeffry; Holman, Thomas

2015-05-01

Couple relationship education (RE) usually is conceived of as relationship enhancement for currently satisfied couples, with a goal of helping couples sustain satisfaction. However, RE also might be useful as a brief, accessible intervention for couples with low satisfaction. Two studies were conducted that tested whether couples with low relationship satisfaction show meaningful gains after RE. Study 1 was a three-condition randomized controlled trial in which 182 couples were randomly assigned to RELATE with Couple CARE (RCC), a flexible delivery education program for couples, or one of two control conditions. Couples with initially low satisfaction receiving RCC showed a moderate increase in relationship satisfaction (d=0.50) relative to the control. In contrast, couples initially high in satisfaction showed little change and there was no difference between RCC and the control conditions. Study 2 was an uncontrolled trial of the Couple Coping Enhancement Training (CCET) administered to 119 couples. Couples receiving CCET that had initially low satisfaction showed a moderate increase in satisfaction (g=.44), whereas initially highly satisfied couples showed no change. Brief relationship education can assist somewhat distressed couples to enhance satisfaction, and has potential as a cost-effective way of enhancing the reach of couple interventions. Copyright © 2015. Published by Elsevier Ltd.

Towards global consensus on outcome measures for atopic eczema research: results of the HOME II meeting.

PubMed

Schmitt, Jochen; Spuls, Phyllis; Boers, Maarten; Thomas, Kim; Chalmers, Joanne; Roekevisch, Evelien; Schram, Mandy; Allsopp, Richard; Aoki, Valeria; Apfelbacher, Christian; Bruijnzeel-Koomen, Carla; Bruin-Weller, Marjolein; Charman, Carolyn; Cohen, Arnon; Dohil, Magdalene; Flohr, Carsten; Furue, Masutaka; Gieler, Uwe; Hooft, Lotty; Humphreys, Rosemary; Ishii, Henrique Akira; Katayama, Ichiro; Kouwenhoven, Willem; Langan, Sinéad; Lewis-Jones, Sue; Merhand, Stephanie; Murota, Hiroyuki; Murrell, Dedee F; Nankervis, Helen; Ohya, Yukihiro; Oranje, Arnold; Otsuka, Hiromi; Paul, Carle; Rosenbluth, Yael; Saeki, Hidehisa; Schuttelaar, Marie-Louise; Stalder, Jean-Francois; Svensson, Ake; Takaoka, Roberto; Wahlgren, Carl-Fredrik; Weidinger, Stephan; Wollenberg, Andreas; Williams, Hywel

2012-09-01

The use of nonstandardized and inadequately validated outcome measures in atopic eczema trials is a major obstacle to practising evidence-based dermatology. The Harmonising Outcome Measures for Eczema (HOME) initiative is an international multiprofessional group dedicated to atopic eczema outcomes research. In June 2011, the HOME initiative conducted a consensus study involving 43 individuals from 10 countries, representing different stakeholders (patients, clinicians, methodologists, pharmaceutical industry) to determine core outcome domains for atopic eczema trials, to define quality criteria for atopic eczema outcome measures and to prioritize topics for atopic eczema outcomes research. Delegates were given evidence-based information, followed by structured group discussion and anonymous consensus voting. Consensus was achieved to include clinical signs, symptoms, long-term control of flares and quality of life into the core set of outcome domains for atopic eczema trials. The HOME initiative strongly recommends including and reporting these core outcome domains as primary or secondary endpoints in all future atopic eczema trials. Measures of these core outcome domains need to be valid, sensitive to change and feasible. Prioritized topics of the HOME initiative are the identification/development of the most appropriate instruments for the four core outcome domains. HOME is open to anyone with an interest in atopic eczema outcomes research. © 2012 John Wiley & Sons A/S.

Step-to-step spatiotemporal variables and ground reaction forces of intra-individual fastest sprinting in a single session.

PubMed

Nagahara, Ryu; Mizutani, Mirai; Matsuo, Akifumi; Kanehisa, Hiroaki; Fukunaga, Tetsuo

2018-06-01

We aimed to investigate the step-to-step spatiotemporal variables and ground reaction forces during the acceleration phase for characterising intra-individual fastest sprinting within a single session. Step-to-step spatiotemporal variables and ground reaction forces produced by 15 male athletes were measured over a 50-m distance during repeated (three to five) 60-m sprints using a long force platform system. Differences in measured variables between the fastest and slowest trials were examined at each step until the 22nd step using a magnitude-based inferences approach. There were possibly-most likely higher running speed and step frequency (2nd to 22nd steps) and shorter support time (all steps) in the fastest trial than in the slowest trial. Moreover, for the fastest trial there were likely-very likely greater mean propulsive force during the initial four steps and possibly-very likely larger mean net anterior-posterior force until the 17th step. The current results demonstrate that better sprinting performance within a single session is probably achieved by 1) a high step frequency (except the initial step) with short support time at all steps, 2) exerting a greater mean propulsive force during initial acceleration, and 3) producing a greater mean net anterior-posterior force during initial and middle acceleration.

A cost-effectiveness analysis of diagnostic strategies for symptomatic patients with ileal pouch-anal anastomosis.

PubMed

Shen, Bo; Shermock, Kenneth M; Fazio, Victor W; Achkar, Jean-Paul; Brzezinski, Aaron; Bevins, Charles L; Bambrick, Marlene L; Remzi, Feza H; Lashner, Bret A

2003-11-01

Pouchitis is often diagnosed based on symptoms and empirically treated with antibiotics (treat-first strategy). However, symptom assessment alone is not reliable for diagnosis, and an initial evaluation with pouch endoscopy (test-first strategy) has been shown to be more accurate. Cost-effectiveness of these strategies has not been compared. The aim of this study was to compare cost-effectiveness of different clinical approaches for patients with symptoms suggestive of pouchitis. Pouchitis was defined as pouchitis disease activity index scores > or =7. The frequency of pouchitis in symptomatic patients with ileal pouch was estimated to be 51%; the efficacy for initial therapy with metronidazole (MTZ) and ciprofloxacin (CIP) was 75% and 85%, respectively. Cost estimates were obtained from Medicare reimbursement data. Six competing strategies (MTZ trial, CIP trial, MTZ-then-CIP trial, CIP-then-MTZ trial, pouch endoscopy with biopsy, and pouch endoscopy without biopsy) were modeled in a decision tree. Costs per correct diagnosis with appropriate treatment were $194 for MTZ trial, $279 for CIP trial, $208 for MTZ-then-CIP trial, $261 for CIP-then-MTZ trial, $352 for pouch endoscopy with biopsy, and $243 for pouch endoscopy without biopsy. Of the two strategies with the lowest cost, the pouch endoscopy without biopsy strategy costs $50 more per patient than the MTZ trial strategy but results in an additional 15 days for early diagnosis and thus initiation of appropriate treatment (incremental cost-effectiveness ratio $3 per additional day gained). The results of base-case analysis were robust in sensitivity analyses. Although the MTZ-trial strategy had the lowest cost, the pouch endoscopy without biopsy strategy was most cost-effective. Therefore, based on its relatively low cost and the avoidance of both diagnostic delay and adverse effects associated with unnecessary antibiotics, pouch endoscopy without biopsy is the recommended strategy among those tested for the diagnosis of pouchitis.

Rationale, timeline, study design, and protocol overview of the therapeutic hypothermia after pediatric cardiac arrest trials.

PubMed

Moler, Frank W; Silverstein, Faye S; Meert, Kathleen L; Clark, Amy E; Holubkov, Richard; Browning, Brittan; Slomine, Beth S; Christensen, James R; Dean, J Michael

2013-09-01

To describe the rationale, timeline, study design, and protocol overview of the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Multicenter randomized controlled trials. Pediatric intensive care and cardiac ICUs in the United States and Canada. Children from 48 hours to 18 years old, who have return of circulation after cardiac arrest, who meet trial eligibility criteria, and whose guardians provide written consent. Therapeutic hypothermia or therapeutic normothermia. From concept inception in 2002 until trial initiation in 2009, 7 years were required to plan and operationalize the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Two National Institute of Child Health and Human Development clinical trial planning grants (R21 and R34) supported feasibility assessment and protocol development. Two clinical research networks, Pediatric Emergency Care Applied Research Network and Collaborative Pediatric Critical Care Research Network, provided infrastructure resources. Two National Heart Lung Blood Institute U01 awards provided funding to conduct separate trials of in-hospital and out-of-hospital cardiac arrest. A pilot vanguard phase that included half the clinical sites began on March 9, 2009, and this was followed by full trial funding through 2015. Over a decade will have been required to plan, design, operationalize, and conduct the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Details described in this report, such as participation of clinical research networks and clinical trial planning grants utilization, may be of utility for individuals who are planning investigator-initiated, federally supported clinical trials.

The role of economics in the QUERI program: QUERI Series

PubMed Central

Smith, Mark W; Barnett, Paul G

2008-01-01

Background The United States (U.S.) Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) has implemented economic analyses in single-site and multi-site clinical trials. To date, no one has reviewed whether the QUERI Centers are taking an optimal approach to doing so. Consistent with the continuous learning culture of the QUERI Program, this paper provides such a reflection. Methods We present a case study of QUERI as an example of how economic considerations can and should be integrated into implementation research within both single and multi-site studies. We review theoretical and applied cost research in implementation studies outside and within VA. We also present a critique of the use of economic research within the QUERI program. Results Economic evaluation is a key element of implementation research. QUERI has contributed many developments in the field of implementation but has only recently begun multi-site implementation trials across multiple regions within the national VA healthcare system. These trials are unusual in their emphasis on developing detailed costs of implementation, as well as in the use of business case analyses (budget impact analyses). Conclusion Economics appears to play an important role in QUERI implementation studies, only after implementation has reached the stage of multi-site trials. Economic analysis could better inform the choice of which clinical best practices to implement and the choice of implementation interventions to employ. QUERI economics also would benefit from research on costing methods and development of widely accepted international standards for implementation economics. PMID:18430199

Evidence basis for integrated management of mineral metabolism in patients with end-stage renal disease.

PubMed

Scialla, Julia J

2018-07-01

Treatment of mineral metabolism is a mainstay of dialysis care including some of its most widely used and costly pharmaceuticals. Although many mineral metabolites are associated with increased risk of mortality, cardiovascular disease, and other morbidities, few clinical trials are available to guide therapy and most focus on single drug approaches. In practice, providers manage many aspects of mineral metabolism simultaneously in integrated treatment approaches that incorporate multiple agents and changes in the dialysis prescription. The present review discusses the rationale and existing evidence for evaluating integrated, as opposed to single drug, approaches in mineral metabolism. Drugs used to treat mineral metabolism have numerous, and sometimes, opposing effects on biochemical risk factors, such as fibroblast growth factor 23 (FGF23), calcium, and phosphorus. Although vitamin D sterols raise these risk markers when lowering parathyroid hormone (PTH), calcimimetics lower them. Trials demonstrate that combined approaches best 'normalize' the mineral metabolism axis in end-stage renal disease (ESRD). Observations embedded within major trials of calcimimetics reveal that adjustment of calcium-based binders and dialysate calcium is a common approach to adverse effects of these drugs with some initial, but inconclusive, evidence that these co-interventions may impact outcomes. The multiple, and often opposing, biochemical effects of many mineral metabolism drugs provides a strong rationale for studying integrated management strategies that consider combinations of drugs and co-interventions as a whole. This remains a current gap in the field with opportunities for clinical trials.

Joint UK societies’ 2014 consensus statement on renal denervation for resistant hypertension

PubMed Central

Lobo, Melvin D; de Belder, Mark A; Cleveland, Trevor; Collier, David; Dasgupta, Indranil; Deanfield, John; Kapil, Vikas; Knight, Charles; Matson, Matthew; Moss, Jonathan; Paton, Julian F R; Poulter, Neil; Simpson, Iain; Williams, Bryan; Caulfield, Mark J

2015-01-01

Resistant hypertension continues to pose a major challenge to clinicians worldwide and has serious implications for patients who are at increased risk of cardiovascular morbidity and mortality with this diagnosis. Pharmacological therapy for resistant hypertension follows guidelines-based regimens although there is surprisingly scant evidence for beneficial outcomes using additional drug treatment after three antihypertensives have failed to achieve target blood pressure. Recently there has been considerable interest in the use of endoluminal renal denervation as an interventional technique to achieve renal nerve ablation and lower blood pressure. Although initial clinical trials of renal denervation in patients with resistant hypertension demonstrated encouraging office blood pressure reduction, a large randomised control trial (Symplicity HTN-3) with a sham-control limb, failed to meet its primary efficacy end point. The trial however was subject to a number of flaws which must be taken into consideration in interpreting the final results. Moreover a substantial body of evidence from non-randomised smaller trials does suggest that renal denervation may have an important role in the management of hypertension and other disease states characterised by overactivation of the sympathetic nervous system. The Joint UK Societies does not recommend the use of renal denervation for treatment of resistant hypertension in routine clinical practice but remains committed to supporting research activity in this field. A number of research strategies are identified and much that can be improved upon to ensure better design and conduct of future randomised studies. PMID:25431461

The role of economics in the QUERI program: QUERI Series.

PubMed

Smith, Mark W; Barnett, Paul G

2008-04-22

The United States (U.S.) Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) has implemented economic analyses in single-site and multi-site clinical trials. To date, no one has reviewed whether the QUERI Centers are taking an optimal approach to doing so. Consistent with the continuous learning culture of the QUERI Program, this paper provides such a reflection. We present a case study of QUERI as an example of how economic considerations can and should be integrated into implementation research within both single and multi-site studies. We review theoretical and applied cost research in implementation studies outside and within VA. We also present a critique of the use of economic research within the QUERI program. Economic evaluation is a key element of implementation research. QUERI has contributed many developments in the field of implementation but has only recently begun multi-site implementation trials across multiple regions within the national VA healthcare system. These trials are unusual in their emphasis on developing detailed costs of implementation, as well as in the use of business case analyses (budget impact analyses). Economics appears to play an important role in QUERI implementation studies, only after implementation has reached the stage of multi-site trials. Economic analysis could better inform the choice of which clinical best practices to implement and the choice of implementation interventions to employ. QUERI economics also would benefit from research on costing methods and development of widely accepted international standards for implementation economics.

A prospective randomised cross-over study of the effect of insulin analogues and human insulin on the frequency of severe hypoglycaemia in patients with type 1 diabetes and recurrent hypoglycaemia (the HypoAna trial): study rationale and design

PubMed Central

2012-01-01

Background Severe hypoglycaemia still represents a significant problem in insulin-treated diabetes. Most patients do not experience severe hypoglycaemia often. However, 20% of patients with type 1 diabetes experience recurrent severe hypoglycaemia corresponding to at least two episodes per year. The effect of insulin analogues on glycaemic control has been documented in large trials, while their effect on the frequency of severe hypoglycaemia is less clear, especially in patients with recurrent severe hypoglycaemia. The HypoAna Trial is designed to investigate whether short-acting and long-acting insulin analogues in comparison with human insulin are superior in reducing the occurrence of severe hypoglycaemic episodes in patients with recurrent hypoglycaemia. This paper reports the study design of the HypoAna Trial. Methods/design The study is a Danish two-year investigator-initiated, prospective, randomised, open, blinded endpoint (PROBE), multicentre, cross-over trial investigating the effect of insulin analogues versus human insulin on the frequency of severe hypoglycaemia in subjects with type 1 diabetes. Patients are randomised to treatment with basal-bolus therapy with insulin detemir / insulin aspart or human NPH insulin / human regular insulin in random order. The major inclusion criterion is history of two or more episodes of severe hypoglycaemia in the preceding year. Discussion In contrast to almost all other studies in this field the HypoAna Trial includes only patients with major problems with hypoglycaemia. The HypoAna Trial will elucidate whether basal-bolus regimen with short-acting and long-acting insulin analogues in comparison with human insulin are superior in reducing occurrence of severe hypoglycaemic episodes in hypoglycaemia prone patients with type 1 diabetes. http://www.clinicaltrials.gov: NCT00346996. PMID:22727048

Outcomes with individual versus group physical therapy for treating urinary incontinence and low back pain: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Robertson, Belinda; Harding, Katherine E

2014-11-01

To evaluate the existing evidence comparing the outcomes of rehabilitation conducted in a group setting and individual therapy for patients receiving rehabilitation. Electronic databases MEDLINE, CINAHL, EMBASE, PEDro, and OT Seeker were searched from the earliest date possible to July 2013. Additional references were identified by manual scanning of reference lists. Randomized controlled trials investigating the effect of group therapy compared with individual therapy for patients receiving rehabilitation were included for review. Two reviewers independently applied the inclusion and exclusion criteria to identify included articles. Initial search identified 1527 potential articles, of which 16 trials with 2337 participants were included in the final review. Data extraction was completed for all included trials by one reviewer, using a customized data extraction form. Data were checked for accuracy by a second reviewer. Trials were independently assessed by 2 reviewers for methodological quality using the PEDro scale. Trials meeting inclusion criteria had been conducted in back pain (n=6 studies), urinary incontinence (n=5), learning disability (n=2), hearing loss (n=1), joint replacement (n=1), and aphasia (n=1). Meta-analysis of physical therapy trials in back pain and urinary incontinence reporting sufficient homogeneous data showed no significant difference in outcomes for group versus individual therapy. These results were also supported by qualitative analysis of the remaining studies in these populations, but there is insufficient evidence to draw conclusions regarding other clinical areas. Evidence shows that providing rehabilitation in a group format results in equivalent clinical outcomes to provision of similar therapy in an individual format in the treatment of back pain and urinary incontinence. There is currently insufficient evidence to draw similar conclusions in other populations or fields of rehabilitation. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Summer School Effects in a Randomized Field Trial

ERIC Educational Resources Information Center

Zvoch, Keith; Stevens, Joseph J.

2013-01-01

This field-based randomized trial examined the effect of assignment to and participation in summer school for two moderately at-risk samples of struggling readers. Application of multiple regression models to difference scores capturing the change in summer reading fluency revealed that kindergarten students randomly assigned to summer school…

EVALUATION OF THE AGDISP AERIAL SPRAY ALGORITHMS IN THE AGDRIFT MODEL

EPA Science Inventory

A systematic evaluation of the AgDISP algorithms, which simulate off-site drift and deposition of aerially applied pesticides, contained in the AgDRIFT model was performed by comparing model simulations to field-trial data collected by the Spray Drift Task Force. Field-trial data...

Research on curcumin: A meta-analysis of potentially malignant disorders.

PubMed

Ara, Syeda Arshiya; Mudda, Jayashree A; Lingappa, Ashok; Rao, Purushottam

2016-01-01

Turmeric has been described in ayurveda, and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Various preclinical, clinical, and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic, as a mediator of chemoresistance, chemopreventive, and as a therapeutic agent. Thus, curcumin a spice once relegated to the kitchen shelf has moved into the clinic and may prove to be "Curecumin." Methodology and Objectives: The focus of this publication is to provide research on curcumin with scientific publications on curcumin indexed in PubMed, Google J-Gate including systematic reviews, randomized controlled trials (RCT's), observational studies, or case series reports for various potentially malignant disorders (PMD's) with special attention to studies on oral submucous fibrosis. This research will be valuable in terms of identifying opportunities to provide recommendations for future research, in terms of the populations to research, the types of interventions needed, the types of outcomes to be measured, the study designs needed, to initiate a pathway for a low-cost research plan for future clinical trials in this field with an emphasis on conducting studies in regions of the world where PMD's are prevalent. There is a lacunae for scientific review of curcumin for PMDs specially on OSMF. Appropriate therapeutic interventions are needed for the initial, intermediate, and advanced stages of the disease. High-quality RCTs should be initiated.

Saccade-related activity in the prefrontal cortex: its role in eye movement control and cognitive functions

PubMed Central

Funahashi, Shintaro

2014-01-01

Prefrontal neurons exhibit saccade-related activity and pre-saccadic memory-related activity often encodes the directions of forthcoming eye movements, in line with demonstrated prefrontal contribution to flexible control of voluntary eye movements. However, many prefrontal neurons exhibit post-saccadic activity that is initiated well after the initiation of eye movement. Although post-saccadic activity has been observed in the frontal eye field, this activity is thought to be a corollary discharge from oculomotor centers, because this activity shows no directional tuning and is observed whenever the monkeys perform eye movements regardless of goal-directed or not. However, prefrontal post-saccadic activities exhibit directional tunings similar as pre-saccadic activities and show context dependency, such that post-saccadic activity is observed only when monkeys perform goal-directed saccades. Context-dependency of prefrontal post-saccadic activity suggests that this activity is not a result of corollary signals from oculomotor centers, but contributes to other functions of the prefrontal cortex. One function might be the termination of memory-related activity after a behavioral response is done. This is supported by the observation that the termination of memory-related activity coincides with the initiation of post-saccadic activity in population analyses of prefrontal activities. The termination of memory-related activity at the end of the trial ensures that the subjects can prepare to receive new and updated information. Another function might be the monitoring of behavioral performance, since the termination of memory-related activity by post-saccadic activity could be associated with informing the correctness of the response and the termination of the trial. However, further studies are needed to examine the characteristics of saccade-related activities in the prefrontal cortex and their functions in eye movement control and a variety of cognitive functions. PMID:25071482

Field Measurement and Model Evaluation Program for Assessment of the Environmental Effects of Military Smokes: Evaluation of Atmospheric Dispersion Models for Fog-Oil Smoke Dispersion

DTIC Science & Technology

1989-02-01

EK 111. TRIAL 19, L 2. \\ (,’, i / ඘ I€ m m B-02 I SMOKE WEEK IV -TRIAL 3 -- LOS1 DOSAGE 0.06 COMESIC U ACT II.......... MAD PUFF 0m0 _LUDWIG (1977...PUFF, AND LUDWIG (1977) WITH FIELD DATA FROM SMOKE WEEK IV. TRIAL 3. LOS1 l (c) For short release times and the calculation of dosages, the randomization

Conjugated Equine Estrogens and Breast Cancer Risk in the Women’s Health Initiative Clinical Trial and Observational Study

PubMed Central

Prentice, Ross L.; Chlebowski, Rowan T.; Stefanick, Marcia L.; Manson, JoAnn E.; Langer, Robert D.; Pettinger, Mary; Hendrix, Susan L.; Hubbell, F. Allan; Kooperberg, Charles; Kuller, Lewis H.; Lane, Dorothy S.; McTiernan, Anne; O’Sullivan, Mary Jo; Rossouw, Jacques E.; Anderson, Garnet L.

2009-01-01

The Women’s Health Initiative randomized controlled trial found a trend (p = 0.09) toward a lower breast cancer risk among women assigned to daily 0.625-mg conjugated equine estrogens (CEEs) compared with placebo, in contrast to an observational literature that mostly reports a moderate increase in risk with estrogenalone preparations. In 1993–2004 at 40 US clinical centers, breast cancer hazard ratio estimates for this CEE regimen were compared between the Women’s Health Initiative clinical trial and observational study toward understanding this apparent discrepancy and refining hazard ratio estimates. After control for prior use of postmenopausal hormone therapy and for confounding factors, CEE hazard ratio estimates were higher from the observational study compared with the clinical trial by 43% (p = 0.12). However, after additional control for time from menopause to first use of postmenopausal hormone therapy, the hazard ratios agreed closely between the two cohorts (p = 0.82). For women who begin use soon after menopause, combined analyses of clinical trial and observational study data do not provide clear evidence of either an overall reduction or an increase in breast cancer risk with CEEs, although hazard ratios appeared to be relatively higher among women having certain breast cancer risk factors or a low body mass index. PMID:18448442

Selection of nontarget arthropod taxa for field research on transgenic insecticidal crops: using empirical data and statistical power.

PubMed

Prasifka, J R; Hellmich, R L; Dively, G P; Higgins, L S; Dixon, P M; Duan, J J

2008-02-01

One of the possible adverse effects of transgenic insecticidal crops is the unintended decline in the abundance of nontarget arthropods. Field trials designed to evaluate potential nontarget effects can be more complex than expected because decisions to conduct field trials and the selection of taxa to include are not always guided by the results of laboratory tests. Also, recent studies emphasize the potential for indirect effects (adverse impacts to nontarget arthropods without feeding directly on plant tissues), which are difficult to predict because of interactions among nontarget arthropods, target pests, and transgenic crops. As a consequence, field studies may attempt to monitor expansive lists of arthropod taxa, making the design of such broad studies more difficult and reducing the likelihood of detecting any negative effects that might be present. To improve the taxonomic focus and statistical rigor of future studies, existing field data and corresponding power analysis may provide useful guidance. Analysis of control data from several nontarget field trials using repeated-measures designs suggests that while detection of small effects may require considerable increases in replication, there are taxa from different ecological roles that are sampled effectively using standard methods. The use of statistical power to guide selection of taxa for nontarget trials reflects scientists' inability to predict the complex interactions among arthropod taxa, particularly when laboratory trials fail to provide guidance on which groups are more likely to be affected. However, scientists still may exercise judgment, including taxa that are not included in or supported by power analyses.

Feasibility of a Centralized Clinical Trials Coverage Analysis: A Joint Initiative of the American Society of Clinical Oncology and the National Cancer Institute.

PubMed

Szczepanek, Connie M; Hurley, Patricia; Good, Marjorie J; Denicoff, Andrea; Willenberg, Kelly; Dawson, Casey; Kurbegov, Dax

2017-06-01

Clinical trial billing compliance is a challenge that is faced by overburdened clinical trials sites. The requirements place institutions and research sites at increased potential for financial risk. To reduce their risk, sites develop a coverage analysis (CA) before opening each trial. For multisite trials, this translates into system-wide redundancies, inconsistencies, trial delays, and potential costs to sites and patients. These factors exacerbate low accrual rates to cancer clinical trials. ASCO and the National Cancer Institute (NCI) collaborated to address this problem. An ASCO Research Community Forum working group proposed the concept of providing centrally developed CAs to research sites at protocol startup. The group collaborated with NCI and billing compliance experts to hold a symposium for key stakeholders to share knowledge, build skills, provide tools to conduct centralized CAs, and strategize about the next steps. Forty-eight attendees, who represented a range of stakeholders, participated in the symposium. As a result of this initiative, NCI directed the Cancer Trials Support Unit to convene a working group with NCI's National Clinical Trials Network (NCTN) and Community Oncology Research Program (NCORP) to develop tools and processes for generating CAs for their trials. A CA template with core elements was developed and is being adapted in a pilot project across NCTN Group and NCORP Research Bases. Centralized CAs for multisite trials-using standardized tools and templates-are feasible. They have the potential to reduce risk for patients and sites, forecast budget needs, and help decrease trial startup times that impede patient access and accrual to clinical trials.

Academic investigator-initiated trials and the challenge of sponsor responsibility: the Cologne Sponsor Model.

PubMed

Georgias, Christine; Grunow, Andrea; Olderog, Miriam; May, Alexander; Paulus, Ursula

2012-12-01

With the amendment to the German Drug Law in 2004, the conduct of clinical trials changed by at least two main aspects: (1) The principles of Good Clinical Practice (GCP) were implemented in the national legislation, and (2) for the first time, the function of the sponsor of a clinical trial and the clinical trial itself have become legally binding definitions. By that, legal differences between industrial and academic clinical trials no longer exist. Clinical trials initiated by investigators have to fulfil the same requirements while the entire sponsor responsibility has to be carried out by the Coordinating Investigator or his institution including implementation of a quality management system according to the GCP. The Cologne Sponsor Model is an effective approach with settings, structures, basic features, action, and reporting lines, as well as funding for clinical trials initiated in an academic environment. The University of Cologne assumes the sponsor responsibility for clinical trials organised by the university researchers according to law. Sponsor's duties are delegated to a central operational unit of the sponsor - the Clinical Trials Center Cologne - which further delegates duties to the Coordinating Investigator. Clinical Trials Center Cologne was established in 2002 to support the performance of clinical trials at the university by offering comprehensive advisory and practical services covering all aspects of study planning and conduct. Furthermore, a specialised division of its quality management department acts as an independent sponsor's Quality Assurance Unit. The Clinical Trials Center Cologne has established a quality management system consisting of different components (1) to enable a reasoned decision to subsequent delegation, (2) for risk-based surveillance of trial conduct (audits, monitoring-checks, and reports), and (3) support and training of the Coordinating Investigator. Double functions of persons and departments in the university environment sometimes make it difficult to define roles in such a model. Therefore, it is necessary to establish clear reporting lines and moreover to monitor regularly and carefully the roles and responsibilities. With the combination of central management and support, control and independence of the researchers, our model represents a 'risk-based' system that offers a sensible option that fulfils the requirements of legal regulations and GCP for trials organised within the university environment.

Randomized Controlled Trial of Nuevo Amanecer: A Peer-delivered Stress Management Intervention for Spanish-speaking Latinas with Breast Cancer

PubMed Central

Nápoles, Anna María; Santoyo-Olsson, Jasmine; Ortiz, Carmen; Gregorich, Steven; Lee, Howard E.; Duron, Ysabel; Graves, Kristi; Luce, Judith A.; McGuire, Peggy; Díaz-Méndez, Marynieves; Stewart, Anita L.

2014-01-01

Background Latinas with breast cancer suffer symptom and psychosocial health disparities. Effective interventions have not been developed for or tested in this population. Purpose We describe community-based participatory research methods used to develop and implement the Nuevo Amanecer program, a culturally tailored, peer-delivered cognitive-behavioral stress management intervention for low-income Spanish-speaking Latinas with breast cancer, and unique considerations in implementing a randomized controlled trial to test the program in community settings. Methods We applied an implementation science framework to delineate the methodological phases used to develop and implement the Nuevo Amanecer program and trial, emphasizing community engagement processes. Results In phase 1, we established project infrastructure: academic and community Co-Principal Investigators, community partners, community advisory board, steering committee, and funding. In phase 2, we identified three program inputs: formative research, a community best practices model, and an evidence-based intervention tested in non-Latinas. In phase 3, we created the new program by integrating and adapting intervention components from the three sources, making adaptations to accommodate low-literacy, Spanish language, cultural factors, community context, and population needs. In phase 4, we built community capacity for the program and trial by training field staff (recruiters and interventionists embedded in community sites), compensating field staff, and creating a system for identifying potential participants. In phase 5, we implemented and monitored the program and trial. Engaging community partners in all phases has resulted in a new, culturally tailored program that is suitable for newly diagnosed Latinas with breast cancer and a trial that is acceptable and supported by community and clinical partners. Lessons Learned Engagement of community-based organizations and cancer survivors as research partners and hiring recruiters and interventionists from the community were critical to successful implementation in community settings. Having culturally and linguistically competent research staff with excellent interpersonal skills facilitated implementation. Facilitating and maintaining excellent communication among community partners was imperative to troubleshoot implementation issues. Randomization was challenging due to community concerns about assigning women to a control group. Patient privacy regulations and the need for extensive outreach to establish relationships between community partners and clinical sites hampered initial recruitment. Limitations These were resource-intensive processes to develop and implement the program that need to be compared to less intensive alternatives. Conclusions Engaging community members in design and implementation of community-based programs and trials enhances cultural appropriateness and congruence with the community context. If the randomized trial demonstrates that the intervention is effective, it will fill a gap in evidence-based programs to address ethnic disparities in quality of life among Spanish-speaking Latinas with breast cancer. PMID:24577971

Conservative versus invasive stable ischemic heart disease management strategies: what do we plan to learn from the ISCHEMIA trial?

PubMed

Cheng-Torres, Kathleen A; Desai, Karan P; Sidhu, Mandeep S; Maron, David J; Boden, William E

2016-01-01

Over the past decade, landmark randomized clinical trials comparing initial management strategies in stable ischemic heart disease (SIHD) have demonstrated no significant reduction in 'hard' end points (all-cause mortality, cardiac death or myocardial infarction) with one strategy versus another. The main advantage derived from early revascularization is improved short-term quality of life. Nonetheless, questions remain regarding how best to manage SIHD patients, such as whether a high-risk subgroup can be identified that may experience a survival or myocardial infarction benefit from early revascularization, and if not, when should diagnostic catheterization and revascularization be performed. The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial is designed to address these questions by randomizing SIHD patients with at least moderate ischemia to an initial conservative strategy of optimal medical therapy or an initial invasive strategy of optimal medical therapy plus cardiac catheterization and revascularization.

[Alzheimer's Therapeutic Research Institute].

PubMed

Shimada, Hiroyuki; Kato, Yuichi; Fujii, Hisako; Mori, Hiroshi

2017-07-01

The Alzheimer's Therapeutic Research Institute (ATRI) was established in 2015 after ATRI director, Paul Aisen, and his fellow experts in therapeutic interventions for Alzheimer's disease (AD) moved from the Alzheimer's Disease Cooperative Study (ADCS) at the University of California to the Keck School of Medicine of the University of Southern California. The National Institute on Aging (NIA) decided to commit $14 million to the ATRI via an Alzheimer's Clinical Trials Consortium (ACTC). The ATRI supports various studies such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer's study ("A4 study"), Alzheimer's Disease Neuroimaging Initiative 3 (ADNI3), Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN), and The Alzheimer's Disease Neuroimaging Initiative-Depression Project (ADNI-D). The ATRI will share all relevant data and materials with the academic community, corporations, and government organizations. The ATRI is overseen by a Data and Safety Monitoring Board (DSMB), which comprises of leading experts in the field of Alzheimer's research and acts independently. The ATRI is slated to play a central role in clinical dementia research in the US in near future.

A Randomized Trial of Telephone Psychotherapy and Pharmacotherapy for Depression: Continuation and Durability of Effects

ERIC Educational Resources Information Center

Ludman, Evette J.; Simon, Gregory E.; Tutty, Steve; Von Korff, Michael

2007-01-01

Randomized trial evidence and expert guidelines are mixed regarding the value of combined pharmacotherapy and psychotherapy as initial treatment for depression. This study describes long-term results of a randomized trial (N = 393) evaluating telephone-based cognitive-behavioral therapy (CBT) plus care management for primary care patients…

A Patient Focused Solution for Enrolling Clinical Trials in Rare and Selective Cancer Indications: A Landscape of Haystacks and Needles

PubMed Central

Lynam, Eric B.; Leaw, Jiin; Wiener, Matthew B.

2013-01-01

Participation of adult cancer patients in US based clinical trials has remained near 3% for decades. Traditional research methodology reaches a small fraction of the target population with a fixed number of predetermined sites. Solutions are needed to ethically increase patient participation and accelerate cancer trial completion. We compared enrollment outcomes of traditional and patient focused research methodologies. A patient prioritized method (Just-In-Time, JIT) was implemented in parallel with traditionally managed sites in three cancer trials. JIT research sites were initiated after candidate patients presented, while traditional sites were initiated in advance. JIT sites enrolled with mean rates no less than, and up to 2.75 fold greater than, traditional sites. Mean patients enrolled per site was comparable (JIT-1.82, traditional-1.78). There were fewer non-enrolling JIT sites (2/28, 7%) compared to traditional sites 19/52, 37%). This retrospective analysis supports JIT as a prospective solution to increase cancer clinical trial enrollment and the efficiency of clinical trial administrative activities. PMID:23990689

High-Throughput Analytical Techniques for the Determination of the Residues of 653 Multiclass Pesticides and Chemical Pollutants in Tea, Part VII: A GC-MS, GC-MS/MS, and LC-MS/MS Study of the Degradation Profiles of Pesticide Residues in Green Tea.

PubMed

Chang, Qiao-Ying; Pang, Guo-Fang; Fan, Chun-Lin; Chen, Hui; Yang, Fang; Li, Jie; Wen, Bi-Fang

2016-11-01

GC-MS, GC-tandem MS (MS/MS), and LC-MS/MS were used to mathematically define the degradation profiles of pesticide residues in two field trials. Nineteen pesticides were studied in the first field trial and 11 in the second. The results of the field trials demonstrated that the degradation profiles of pesticide residues in green tea can be described with power functions to successfully estimate the amount of time, following pesticide application, pesticide residues appearing in tea in concentrations at and/or above the maximum residue limit (MRL) decrease to concentrations below the MRL. Stability tests on green tea samples stored at room temperature were conducted to determine whether pesticide-incurred green tea samples prepared according to the method used in the field trials would be suitable for the preparation of reference standards for laboratory-proficiency testing trials. This paper reports the results of a GC-MS, GC-MS/MS, and LC-MS/MS study, as well as the suitability of the samples prepared under these conditions for use as pesticide reference standards in tea analysis.

Impact of Different Visual Field Testing Paradigms on Sample Size Requirements for Glaucoma Clinical Trials.

PubMed

Wu, Zhichao; Medeiros, Felipe A

2018-03-20

Visual field testing is an important endpoint in glaucoma clinical trials, and the testing paradigm used can have a significant impact on the sample size requirements. To investigate this, this study included 353 eyes of 247 glaucoma patients seen over a 3-year period to extract real-world visual field rates of change and variability estimates to provide sample size estimates from computer simulations. The clinical trial scenario assumed that a new treatment was added to one of two groups that were both under routine clinical care, with various treatment effects examined. Three different visual field testing paradigms were evaluated: a) evenly spaced testing, b) United Kingdom Glaucoma Treatment Study (UKGTS) follow-up scheme, which adds clustered tests at the beginning and end of follow-up in addition to evenly spaced testing, and c) clustered testing paradigm, with clusters of tests at the beginning and end of the trial period and two intermediary visits. The sample size requirements were reduced by 17-19% and 39-40% using the UKGTS and clustered testing paradigms, respectively, when compared to the evenly spaced approach. These findings highlight how the clustered testing paradigm can substantially reduce sample size requirements and improve the feasibility of future glaucoma clinical trials.

Initiation of soil formation in weathered sulfidic Cu-Pb-Zn tailings under subtropical and semi-arid climatic conditions.

PubMed

You, Fang; Dalal, Ram; Huang, Longbin

2018-08-01

Field evidence has been scarce about soil (or technosol) formation and direct phytostabilization of base metal mine tailings under field conditions. The present study evaluated key attributes of soil formation in weathered and neutral Cu-Pb-Zn tailings subject to organic amendment (WC: woodchips) and colonization of pioneer native plant species (mixed native woody and grass plant species) in a 2.5-year field trial under subtropical and semi-arid climatic conditions. Key soil indicators of engineered soil formation process were characterized, including organic carbon fractions, aggregation, microbial community and key enzymatic activities. The majority (64-87%) of the OC was stabilized in microaggregate or organo-mineral complexes in the amended tailings. The levels of OC and water soluble OC were elevated by 2-3 folds across the treatments, with the highest level in the treatment of WC and plant colonization (WC+P). Specifically, the WC+P treatment increased the proportion of water stable macroaggregates. Plants further contributed to the N rich organic matter in the tailings, favouring organo-mineral interactions and organic stabilization. Besides, the plants played a major role in boosting microbial biomass and activities in the treated tailings. WC and plants enhanced the contents of organic carbon (OC) associated with aggregates (e.g., physically protected OC), formation of water-stable aggregates (e.g., micro and macroaggregates), chemical buffering capacity (e.g., cation exchange capacity). Microbial community and enzymatic activities were also stimulated in the amended tailings. The present results showed that the formation of functional technosol was initiated in the eco-engineered and weathered Cu-Pb-Zn tailings under field conditions for direct phytostabilization. Copyright © 2018 Elsevier Ltd. All rights reserved.

Implementing universal HIV treatment in a high HIV prevalence and rural South African setting – Field experiences and recommendations of health care providers

PubMed Central

Gumede, Dumile; Boyer, Sylvie; Pillay, Deenan; Dabis, François; Seeley, Janet; Orne-Gliemann, Joanna

2017-01-01

Background We aimed to describe the field experiences and recommendations of clinic-based health care providers (HCP) regarding the implementation of universal antiretroviral therapy (ART) in rural KwaZulu-Natal, South Africa. Methods In Hlabisa sub-district, the local HIV programme of the Department of Health (DoH) is decentralized in 18 clinics, where ART was offered at a CD4 count ≤500 cells/μL from January 2015 to September 2016. Within the ANRS 12249 TasP trial, implemented in part of the sub-district, universal ART (no eligibility criteria) was offered in 11 mobile clinics between March 2012 and June 2016. A cross-sectional qualitative survey was conducted in April–July 2016 among clinic-based nurses and counsellors providing HIV care in the DoH and TasP trial clinics. In total, 13 individual interviews and two focus groups discussions (including 6 and 7 participants) were conducted, audio-recorded, transcribed, and thematically analyzed. Results All HCPs reported an overall good experience of delivering ART early in the course of HIV infection, with most patients willing to initiate ART before being symptomatic. Yet, HCPs underlined that not feeling sick could challenge early ART initiation and adherence, and thus highlighted the need to take time for counselling as an important component to achieve universal ART. HCPs also foresaw logistical challenges of universal ART, and were especially concerned about increasing workload and ART shortage. HCPs finally recommended the need to strengthen the existing model of care to facilitate access to ART, e.g., community-based and integrated HIV services. Conclusions The provision of universal ART is feasible and acceptable according to HCPs in this rural South-African area. However their experiences suggest that universal ART, and more generally the 90-90-90 UNAIDS targets, will be difficult to achieve without the implementation of new models of health service delivery. PMID:29155832

Implementing universal HIV treatment in a high HIV prevalence and rural South African setting - Field experiences and recommendations of health care providers.

PubMed

Plazy, Melanie; Perriat, Delphine; Gumede, Dumile; Boyer, Sylvie; Pillay, Deenan; Dabis, François; Seeley, Janet; Orne-Gliemann, Joanna

2017-01-01

We aimed to describe the field experiences and recommendations of clinic-based health care providers (HCP) regarding the implementation of universal antiretroviral therapy (ART) in rural KwaZulu-Natal, South Africa. In Hlabisa sub-district, the local HIV programme of the Department of Health (DoH) is decentralized in 18 clinics, where ART was offered at a CD4 count ≤500 cells/μL from January 2015 to September 2016. Within the ANRS 12249 TasP trial, implemented in part of the sub-district, universal ART (no eligibility criteria) was offered in 11 mobile clinics between March 2012 and June 2016. A cross-sectional qualitative survey was conducted in April-July 2016 among clinic-based nurses and counsellors providing HIV care in the DoH and TasP trial clinics. In total, 13 individual interviews and two focus groups discussions (including 6 and 7 participants) were conducted, audio-recorded, transcribed, and thematically analyzed. All HCPs reported an overall good experience of delivering ART early in the course of HIV infection, with most patients willing to initiate ART before being symptomatic. Yet, HCPs underlined that not feeling sick could challenge early ART initiation and adherence, and thus highlighted the need to take time for counselling as an important component to achieve universal ART. HCPs also foresaw logistical challenges of universal ART, and were especially concerned about increasing workload and ART shortage. HCPs finally recommended the need to strengthen the existing model of care to facilitate access to ART, e.g., community-based and integrated HIV services. The provision of universal ART is feasible and acceptable according to HCPs in this rural South-African area. However their experiences suggest that universal ART, and more generally the 90-90-90 UNAIDS targets, will be difficult to achieve without the implementation of new models of health service delivery.

Moving forward through consensus: protocol for a modified Delphi approach to determine the top research priorities in the field of orthopaedic oncology.

PubMed

Schneider, Patricia; Evaniew, Nathan; Rendon, Juan Sebastian; McKay, Paula; Randall, R Lor; Turcotte, Robert; Vélez, Roberto; Bhandari, Mohit; Ghert, Michelle

2016-05-24

Orthopaedic oncology researchers face several obstacles in the design and execution of randomised controlled trials, including finite fiscal resources to support the rising costs of clinical research and insufficient patient volume at individual sites. As a result, high-quality research to guide clinical practice has lagged behind other surgical subspecialties. A focused approach is imperative to design a research programme that is economical, streamlined and addresses clinically relevant endpoints. The primary objective of this study will be to use a consensus-based approach to identify research priorities for international clinical trials in orthopaedic oncology. We will conduct a 3-phase modified Delphi method consisting of 2 sequential rounds of anonymous web-based questionnaires (phases I and II), and an in-person consensus meeting (phase III). Participants will suggest research questions that they believe are of particular importance to the field (phase I), and individually rate each proposed question on 5 criteria (phase II). Research questions that meet predetermined consensus thresholds will be brought forward to the consensus meeting (phase III) for discussion by an expert panel. Following these discussions, the expert panel will be asked to assign scores for each research question, and research questions meeting predetermined criteria will be brought forward for final ranking. The expert panel will then be asked to rank the top 3 research questions, and these 3 research questions will be distributed to the initial group of participants for validation. An ethics application is currently under review with the Hamilton Integrated Research Ethics Board in Hamilton, Ontario, Canada. The results of this initiative will be disseminated through peer-reviewed publications and conference presentations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

SU-F-T-240: EPID-Based Quality Assurance for Dosimetric Credentialing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miri, N; Lehmann, J; Vial, P

Purpose: We propose a novel dosimetric audit method for clinical trials using EPID measurements at each center and a standardized EPID to dose conversion algorithm. The aim of this work is to investigate the applicability of the EPID method to different linear accelerator, EPID and treatment planning system (TPS) combinations. Methods: Combination of delivery and planning systems were three Varian linacs including one Pinnacle and two Eclipse TPS and, two ELEKTA linacs including one Pinnacle and one Monaco TPS. All Varian linacs had the same EPID structure and similarly for the ELEKTA linacs. Initially, dose response of the EPIDs wasmore » investigated by acquiring integrated pixel value (IPV) of the central area of 10 cm2 images versus MUs, 5-400 MU. Then, the EPID to dose conversion was investigated for different system combinations. Square field size images, 2, 3, 4, 6, 10, 15, 20, 25 cm2 acquired by all systems were converted to dose at isocenter of a virtual flat phantom then the dose was compared to the corresponding TPS dose. Results: All EPIDs showed a relatively linear behavior versus MU except at low MUs which showed irregularities probably due to initial inaccuracies of irradiation. Furthermore, for all the EPID models, the model predicted TPS dose with a mean dose difference percentage of 1.3. However the model showed a few inaccuracies for ELEKTA EPID images at field sizes larger than 20 cm2. Conclusion: The EPIDs demonstrated similar behavior versus MU and the model was relatively accurate for all the systems. Therefore, the model could be employed as a global dosimetric method to audit clinical trials. Funding has been provided from Department of Radiation Oncology, TROG Cancer Research and the University of Newcastle. Narges Miri is a recipient of a University of Newcastle postgraduate scholarship.« less

Responses of Conophthorus spp. (Coleoptera: Scolytidae) to behavioral chemicals in field trials: a transcontinental perspective

Treesearch

Nancy G. Rappaport; John D. Stein; Adolfo Arturo del Rio Mora; Gary DeBarr; Peter de Groot; Sylvia Mori

2000-01-01

We tested six behavioral chemicals, pityol, conophthorin, 4-allylanisole, verbenone, 2-hexenol, and á-pinene, in a series of field trials directed at six combinations of Conophthorus Hopkins - Pinus L. spp. (Pinaceae) in sites distributed across North America. Beetle - host tree combinations included Conophthorus...

Implementing Interactive Telecommunications Services. Final Report on Problems Which Arise During Implementation of Field Trials and Demonstration Projects.

ERIC Educational Resources Information Center

Elton, Martin C. J.; Carey, John

Intended primarily for use by individuals about to assume responsibility for the implementation of field trials and demonstration projects built around interactive telecommunication systems, this report provides brief descriptions of 20 telemedicine projects, 12 teleconferencing projects, and seven involving two-way applications of cable…

Foliar fungicides on alfalfa: 2012 University extension field trial results from Minnesota and Wisconsin

USDA-ARS?s Scientific Manuscript database

To answer the increasing number of questions received regarding the use of foliar fungicide on alfalfa, a group of Extension and USDA Agricultural Research Station staff in southeastern Minnesota and Wisconsin worked together to conduct field research trials to examine the benefit of using a foliar ...

Simple and conditional visual discrimination with wheel running as reinforcement in rats.

PubMed

Iversen, I H

1998-09-01

Three experiments explored whether access to wheel running is sufficient as reinforcement to establish and maintain simple and conditional visual discriminations in nondeprived rats. In Experiment 1, 2 rats learned to press a lit key to produce access to running; responding was virtually absent when the key was dark, but latencies to respond were longer than for customary food and water reinforcers. Increases in the intertrial interval did not improve the discrimination performance. In Experiment 2, 3 rats acquired a go-left/go-right discrimination with a trial-initiating response and reached an accuracy that exceeded 80%; when two keys showed a steady light, pressing the left key produced access to running whereas pressing the right key produced access to running when both keys showed blinking light. Latencies to respond to the lights shortened when the trial-initiation response was introduced and became much shorter than in Experiment 1. In Experiment 3, 1 rat acquired a conditional discrimination task (matching to sample) with steady versus blinking lights at an accuracy exceeding 80%. A trial-initiation response allowed self-paced trials as in Experiment 2. When the rat was exposed to the task for 19 successive 24-hr periods with access to food and water, the discrimination performance settled in a typical circadian pattern and peak accuracy exceeded 90%. When the trial-initiation response was under extinction, without access to running, the circadian activity pattern determined the time of spontaneous recovery. The experiments demonstrate that wheel-running reinforcement can be used to establish and maintain simple and conditional visual discriminations in nondeprived rats.

The status of paediatric medicines initiatives around the world--What has happened and what has not?

PubMed

Hoppu, Kalle; Anabwani, Gabriel; Garcia-Bournissen, Facundo; Gazarian, Madlen; Kearns, Gregory L; Nakamura, Hidefumi; Peterson, Robert G; Sri Ranganathan, Shalini; de Wildt, Saskia N

2012-01-01

This review was conducted to examine the current status of paediatric medicines initiatives across the globe. The authors made a non-systematic descriptive review of current world situation. Two regions, the United States (US) and the European Union (EU), and the World Health Organization (WHO) have introduced strong paediatric initiatives to improve children's health through improving access to better paediatric medicines. The experience from the US initiative indicates that it is possible to stimulate development and study of paediatric medicines and provide important new information for improvement of paediatric therapy. The early results from the EU initiative are similarly encouraging. In Canada, Japan, Australia and other developed countries, specific paediatric medicines initiatives have been less extensive and weaker, with modest results. Disappointingly, current evidence suggests that results from clinical trials outside the US often do not benefit children in the country in which the trials were largely conducted. Pharmaceutical companies that have derived a financial benefit commensurate with the cost of doing the paediatric trials in one country do not seem to be making the results of these trials available to all countries if there is no financial incentive to the company. The WHO campaign 'make medicines child size' has produced substantive accomplishments in building improved foundations to improve mechanisms that will enhance children's access to critical medicines in resource-limited settings. However, practically all of this work has been performed using an amalgamation of short-term funding from a variety of sources as opposed to a sustained, programmatic commitment. Although much still needs to be done, it's clear that with concerted efforts and appropriate resources, change is possible but slow. Retaining and fostering public and political interest in paediatric medicines is challenging, but pivotal for success.

Spatial and reversal learning in the Morris water maze are largely resistant to six hours of REM sleep deprivation following training

PubMed Central

Walsh, Christine M.; Booth, Victoria; Poe, Gina R.

2011-01-01

This first test of the role of REM (rapid eye movement) sleep in reversal spatial learning is also the first attempt to replicate a much cited pair of papers reporting that REM sleep deprivation impairs the consolidation of initial spatial learning in the Morris water maze. We hypothesized that REM sleep deprivation following training would impair both hippocampus-dependent spatial learning and learning a new target location within a familiar environment: reversal learning. A 6-d protocol was divided into the initial spatial learning phase (3.5 d) immediately followed by the reversal phase (2.5 d). During the 6 h following four or 12 training trials/day of initial or reversal learning phases, REM sleep was eliminated and non-REM sleep left intact using the multiple inverted flowerpot method. Contrary to our hypotheses, REM sleep deprivation during four or 12 trials/day of initial spatial or reversal learning did not affect training performance. However, some probe trial measures indicated REM sleep-deprivation–associated impairment in initial spatial learning with four trials/day and enhancement of subsequent reversal learning. In naive animals, REM sleep deprivation during normal initial spatial learning was followed by a lack of preference for the subsequent reversal platform location during the probe. Our findings contradict reports that REM sleep is essential for spatial learning in the Morris water maze and newly reveal that short periods of REM sleep deprivation do not impair concurrent reversal learning. Effects on subsequent reversal learning are consistent with the idea that REM sleep serves the consolidation of incompletely learned items. PMID:21677190

NCI and the Precision Medicine Initiative®

Cancer.gov

NCI's activities related to precision medicine focuses on new and expanded precision medicine clinical trials; mechanisms to overcome drug resistance to cancer treatments; and developing a shared digital repository of precision medicine trials data.

Monkey primary somatosensory cortical activity during the early reaction time period differs with cues that guide movements

PubMed Central

Liu, Yu; Denton, John M.; Nelson, Randall J.

2009-01-01

Vibration-related neurons in monkey primary somatosensory cortex (SI) discharge rhythmically when vibratory stimuli are presented. It remains unclear how functional information carried by vibratory inputs is coded in rhythmic neuronal activity. In the present study, we compared neuronal activity during wrist movements in response to two sets of cues. In the first, movements were guided by vibratory cue only (VIB trials). In the second, movements were guided by simultaneous presentation of both vibratory and visual cues (COM trials). SI neurons were recorded extracellularly during both wrist extensions and flexions. Neuronal activity during the instructed delay period (IDP) and the early reaction time period (RTP) were analyzed. A total of 96 cases from 48 neurons (each neuron contributed two cases, one each for extension and flexion) showed significant vibration entrainment during the early RTPs, as determined by circular statistics (Rayleigh test). Of these, 50 cases had cutaneous (CUTA) and 46 had deep (DEEP) receptive fields. The CUTA neurons showed lower firing rates during the IDPs and greater firing rate changes during the early RTPs when compared with the DEEP neurons. The CUTA neurons also demonstrated decreases in activity entrainment during VIB trials when compared with COM trials. For the DEEP neurons, the difference of entrainment between VIB and COM trials was not statistically significant. The results suggest that somatic vibratory input is coded by both the firing rate and the activity entrainment of the CUTA neurons in SI. The results also suggest that when vibratory inputs are required for successful task completion, the activity of the CUTA neurons increases but the entrainment degrades. The DEEP neurons may be tuned before movement initiation for processing information encoded by proprioceptive afferents. PMID:18288475

Salt-Rich Selenium for Prevention and Control Children with Kashin-Beck Disease: a Meta-analysis of Community-Based Trial.

PubMed

Yu, Fang-fang; Han, Jing; Wang, Xi; Fang, Hua; Liu, Huan; Guo, Xiong

2016-03-01

Kashin-Beck disease (KBD) in western China is not well controlled. The objective of this study is to evaluate prevention and control children with KBD through a meta-analysis of a community-based trial. Web of knowledge, PubMed, Elsevier, the Chinese National Knowledge Infrastructure (CNKI), VIP and Wanfang data had been electronically searched up to February 2015. Search terms included the trial terms "Salt rich selenium" and "Kashin-Beck disease." Eligible studies were prospective trials of salt-rich selenium in endemic villages. Data extraction was performed by two authors using predefined data fields that also included quality evaluation. Of 292 potentially relevant articles initially screened, reporting 11 community-based trials with a total enrollment of 2652 participants were included, from five provinces in China. The pooled odds ratios (OR) and 95 % confidence intervals (CI) of primary prevention in healthy children were 0.16 and 0.08∼0.33, respectively. The OR and 95 % CI of clinical improvement in KBD children were 6.57 and 3.33∼12.93, respectively. The OR of repairing rate of metaphysis lesions was 5.53 (95 % CI 2.92∼10.47) based on X-ray film, which was statistically significantly different in favor of salt-rich selenium. The combined standard mean difference (SMD) of selenium content in hair was 2.54 (95 % CI 1.21∼3.87) which was significantly higher in selenium group. Current evidence showed that supplement salt-rich selenium was effective in reducing new incidence in healthy children and clinical improvement including repairing metaphysis lesions instead of repairing distal end of phalanx lesions in KBD children.

Monkey primary somatosensory cortical activity during the early reaction time period differs with cues that guide movements.

PubMed

Liu, Yu; Denton, John M; Nelson, Randall J

2008-05-01

Vibration-related neurons in monkey primary somatosensory cortex (SI) discharge rhythmically when vibratory stimuli are presented. It remains unclear how functional information carried by vibratory inputs is coded in rhythmic neuronal activity. In the present study, we compared neuronal activity during wrist movements in response to two sets of cues. In the first, movements were guided by vibratory cue only (VIB trials). In the second, movements were guided by simultaneous presentation of both vibratory and visual cues (COM trials). SI neurons were recorded extracellularly during both wrist extensions and flexions. Neuronal activity during the instructed delay period (IDP) and the early reaction time period (RTP) were analyzed. A total of 96 cases from 48 neurons (each neuron contributed two cases, one each for extension and flexion) showed significant vibration entrainment during the early RTPs, as determined by circular statistics (Rayleigh test). Of these, 50 cases had cutaneous (CUTA) and 46 had deep (DEEP) receptive fields. The CUTA neurons showed lower firing rates during the IDPs and greater firing rate changes during the early RTPs when compared with the DEEP neurons. The CUTA neurons also demonstrated decreases in activity entrainment during VIB trials when compared with COM trials. For the DEEP neurons, the difference of entrainment between VIB and COM trials was not statistically significant. The results suggest that somatic vibratory input is coded by both the firing rate and the activity entrainment of the CUTA neurons in SI. The results also suggest that when vibratory inputs are required for successful task completion, the activity of the CUTA neurons increases but the entrainment degrades. The DEEP neurons may be tuned before movement initiation for processing information encoded by proprioceptive afferents.

Project EX: A Program of Empirical Research on Adolescent Tobacco Use Cessation

PubMed Central

Sussman, Steve; McCuller, William J; Zheng, Hong; Pfingston, Yvonne M; Miyano, James; Dent, Clyde W

2004-01-01

This paper presents the Project EX research program. The historical background for Project EX is presented, including a brief summary of reasons youth fail to quit tobacco use, the disappointing status of previous cessation research, and the teen cessation trial that provided the template for the current project (Project TNT). Next, program development studies for Project EX are described. Through use of focus groups, a theme study (concept evaluation of written activity descriptions), a component study, and pilot studies, an eight-session program was developed. This program involves novel activities (e.g., "talk show enactments," games, and alternative medicine-type activities such as yoga and meditation) in combination with motivation enhancement and cognitive-behavioral strategies to motivate and instruct in cessation initiation and maintenance efforts. The outcomes of the first experimental trial of Project EX, a school-based clinic program, are described, followed by a posthoc analysis of its effects mediation. A second EX study, a multiple baseline single group pilot study design in Wuhan, China, is described next. Description of a second experimental trial follows, which tested EX with nicotine gum versus a natural herb. A third experimental trial that tests a classroom prevention/cessation version of EX is then introduced. Finally, the implications of this work are discussed. The intent-to-treat quit rate for Project EX is approximately 15% across studies, double that of a standard care comparison. Effects last up to a six-month post-program at regular and alternative high schools. Through a systematic protocol of empirical program development and field trials, an effective and replicable model teen tobacco use cessation program is established. Future cessation work might expand on this work.

Project EX: A Program of Empirical Research on Adolescent Tobacco Use Cessation

PubMed Central

Sussman, Steve; McCuller, William J; Zheng, Hong; Pfingston, Yvonne M; Miyano, James; Dent, Clyde W

2004-01-01

This paper presents the Project EX research program. The historical background for Project EX is presented, including a brief summary of reasons youth fail to quit tobacco use, the disappointing status of previous cessation research, and the teen cessation trial that provided the template for the current project (Project TNT). Next, program development studies for Project EX are described. Through use of focus groups, a theme study (concept evaluation of written activity descriptions), a component study, and pilot studies, an eight-session program was developed. This program involves novel activities (e.g., "talk show enactments," games, and alternative medicine-type activities such as yoga and meditation) in combination with motivation enhancement and cognitive-behavioral strategies to motivate and instruct in cessation initiation and maintenance efforts. The outcomes of the first experimental trial of Project EX, a school-based clinic program, are described, followed by a posthoc analysis of its effects mediation. A second EX study, a multiple baseline single group pilot study design in Wuhan, China, is described next. Description of a second experimental trial follows, which tested EX with nicotine gum versus a natural herb. A third experimental trial that tests a classroom prevention/cessation version of EX is then introduced. Finally, the implications of this work are discussed. The intent-to-treat quit rate for Project EX is approximately 15% across studies, double that of a standard care comparison. Effects last up to a six-month post-program at regular and alternative high schools. Through a systematic protocol of empirical program development and field trials, an effective and replicable model teen tobacco use cessation program is established. Future cessation work might expand on this work. PMID:19570278

Commentary on "A roadmap for the prevention of dementia II. Leon Thal Symposium 2008." The Multidomain Alzheimer Preventive Trial (MAPT): a new approach to the prevention of Alzheimer's disease.

PubMed

Gillette-Guyonnet, Sophie; Andrieu, Sandrine; Dantoine, Thierry; Dartigues, Jean-François; Touchon, Jacques; Vellas, B

2009-03-01

Because no effective curative approaches are available, preventive approaches in the field of Alzheimer's disease (AD) are needed. We present the design of the ongoing Multidomain Alzheimer Preventive Trial (MAPT) Study. Several previous studies suggested that many factors may be involved in the occurrence of AD at late ages. Because of the probable multifactorial nature of AD, it seems logical to initiate multidomain interventions to examine their potential synergistic effects. The MAPT Study aims to evaluate the efficacy of a multidomain intervention (nutritional, physical, and cognitive training) and omega 3 treatment in the prevention of cognitive decline in frail elderly persons aged 70 years or over. The study also collects imaging and biological data that could be used in future AD prevention and treatment trials. The MAPT Study is a 3-year, randomized, controlled trial conducted by university hospital practitioners specializing in memory disorders in four French cities (Bordeaux, Limoges, Montpellier, and Toulouse). The study plans to enroll 1200 frail elderly subjects on the basis of at least one of the following criteria: subjective memory complaint spontaneously expressed to a general practitioner, limitation in one instrumental activity of daily living (IADL), and slow walking speed. To demonstrate the protective effect of interventions, subjects are randomized into one of the following four groups: omega 3 alone, multidomain intervention alone, omega 3 plus multidomain intervention, or placebo (n = 300 each). The principal outcome measure is a change in cognitive function at 3 years, as determined by the Grober and Buschke Test. The MAPT Study is the first preventive trial involving multidomain interventions. Final results should be available in 2013.

Development of outcome measures for large-vessel vasculitis for use in clinical trials: opportunities, challenges, and research agenda.

PubMed

Direskeneli, Haner; Aydin, Sibel Z; Kermani, Tanaz A; Matteson, Eric L; Boers, Maarten; Herlyn, Karen; Luqmani, Raashid A; Neogi, Tuhina; Seo, Philip; Suppiah, Ravi; Tomasson, Gunnar; Merkel, Peter A

2011-07-01

Giant cell (GCA) and Takayasu's arteritis (TAK) are 2 forms of large-vessel vasculitis (LVV) that involve the aorta and its major branches. GCA has a predilection for the cranial branches, while TAK tends to affect the extracranial branches. Both disorders may also cause nonspecific constitutional symptoms. Although some clinical features are more common in one or the other disorder and the ages of initial presentation differ substantially, there is enough clinical and histopathologic overlap between these disorders that some investigators suggest GCA and TAK may be 2 processes within the spectrum of a single disease. There have been few randomized therapeutic trials completed in GCA, and none in TAK. The lack of therapeutic trials in LVV is only partially explained by the rarity of these diseases. It is likely that the lack of well validated outcome measures for LVV and uncertainties regarding trial design contribute to the paucity of trials for these diseases. An initiative to develop a core set of outcome measures for use in clinical trials of LVV was launched by the international OMERACT Vasculitis Working Group in 2009 and subsequently endorsed by the OMERACT community at the OMERACT 10 meeting. Aims of this initiative include: (1) to review the literature and existing data related to outcome assessments in LVV; (2) to obtain the opinion of experts and patients on disease content; and (3) to formulate a research agenda to facilitate a more data-based approach to outcomes development.

Development of Outcome Measures for Large-vessel Vasculitis for Use in Clinical Trials: Opportunities, Challenges, and Research Agenda

PubMed Central

DIRESKENELI, HANER; AYDIN, SIBEL Z.; KERMANI, TANAZ A.; MATTESON, ERIC L.; BOERS, MAARTEN; HERLYN, KAREN; LUQMANI, RAASHID A.; NEOGI, TUHINA; SEO, PHILIP; SUPPIAH, RAVI; TOMASSON, GUNNAR; MERKEL, PETER A.

2013-01-01

Giant cell (GCA) and Takayasu’s arteritis (TAK) are 2 forms of large-vessel vasculitis (LVV) that involve the aorta and its major branches. GCA has a predilection for the cranial branches, while TAK tends to affect the extracranial branches. Both disorders may also cause nonspecific constitutional symptoms. Although some clinical features are more common in one or the other disorder and the ages of initial presentation differ substantially, there is enough clinical and histopathologic overlap between these disorders that some investigators suggest GCA and TAK may be 2 processes within the spectrum of a single disease. There have been few randomized therapeutic trials completed in GCA, and none in TAK. The lack of therapeutic trials in LVV is only partially explained by the rarity of these diseases. It is likely that the lack of well validated outcome measures for LVV and uncertainties regarding trial design contribute to the paucity of trials for these diseases. An initiative to develop a core set of outcome measures for use in clinical trials of LVV was launched by the international OMERACT Vasculitis Working Group in 2009 and subsequently endorsed by the OMERACT community at the OMERACT 10 meeting. Aims of this initiative include: (1) to review the literature and existing data related to outcome assessments in LVV; (2) to obtain the opinion of experts and patients on disease content; and (3) to formulate a research agenda to facilitate a more data-based approach to outcomes development. PMID:21724719

Predictive Associations of Music, Anxiety, and Sedative Exposure on Mechanical Ventilation Weaning Trials

PubMed Central

Hetland, Breanna; Lindquist, Ruth; Weinert, Craig R.; Peden-McAlpine, Cynthia; Savik, Kay; Chlan, Linda

2017-01-01

Background Weaning from mechanical ventilation requires increased respiratory effort, which can heighten anxiety and later prolong the need for mechanical ventilation. Objectives To examine the predictive associations of music intervention, anxiety, sedative exposure, and patients’ characteristics on time to initiation and duration of weaning trials of patients receiving mechanical ventilation. Methods A descriptive, correlational design was used for a secondary analysis of data from a randomized trial. Music listening was defined as self-initiated, patient-directed music via headphones. Anxiety was measured daily with a visual analog scale. Sedative exposure was operationalized as a daily sedation intensity score and a sedative dose frequency. Analyses consisted of descriptive statistics, graphing, survival analysis, Cox proportional hazards regression, and linear regression. Results Of 307 patients, 52% were women and 86% were white. Mean age was 59.3 (SD, 14.4) years, mean Acute Physiology and Chronic Health Evaluation III score was 62.9 (SD, 21.6), mean duration of ventilatory support was 8 (range, 1–52) days, and mean stay in the intensive care unit was 18 (range, 2–71) days. Music listening, anxiety levels, and sedative exposure did not influence time to initial weaning trial or duration of trials. Clinical factors of illness severity, days of weaning trials, and tracheostomy placement influenced weaning patterns in this sample. Conclusions Prospective studies of music intervention and other psychophysiological factors during weaning from mechanical ventilation are needed to better understand factors that promote successful weaning. PMID:28461543

Olfactory source localization in the open field using one or both nostrils.

PubMed

Welge-Lussen, A; Looser, G L; Westermann, B; Hummel, T

2014-03-01

This study aims to examine humans ́ abilities to localize odorants within the open field. Young participants were tested on a localization task using a relatively selective olfactory stimulus (2-phenylethyl-alcohol, PEA) and cineol, an odorant with a strong trigeminal component. Participants were blindfolded and had to localize an odorant source at 2 m distance (far-field condition) and a 0.4 m distance (near-field condition) with either two nostrils open or only one open nostril. For the odorant with trigeminal properties, the number of correct trials did not differ when one or both nostrils were used, while more PEA localization trials were correctly completed with both rather than one nostril. In the near-field condition, correct localization was possible in 72-80% of the trials, irrespective of the odorant and the number of nostrils used. Localization accuracy, measured as spatial deviation from the olfactory source, was significantly higher in the near-field compared to the far-field condition, but independent of the odorant being localized. Odorant localization within the open field is difficult, but possible. In contrast to the general view, humans seem to be able to exploit the two-nostril advantage with increasing task difficulty.

First generation leishmaniasis vaccines: a review of field efficacy trials.

PubMed

Noazin, Sassan; Modabber, Farrokh; Khamesipour, Ali; Smith, Peter G; Moulton, Lawrence H; Nasseri, Kiumarss; Sharifi, Iraj; Khalil, Eltahir A G; Bernal, Ivan Dario Velez; Antunes, Carlos M F; Kieny, Marie Paule; Tanner, Marcel

2008-12-09

First generation candidate vaccines against leishmaniasis, prepared using inactivated whole parasites as their main ingredient, were considered as promising because of their relative ease of production and low cost. These vaccines have been the subject of many investigations over several decades and are the only leishmaniasis vaccine candidates which have undergone phase 3 clinical trial evaluation. Although the studies demonstrated the safety of the vaccines and several studies showed reasonable immunogenicity and some indication of protection, an efficacious prophylactic vaccine is yet to be identified. Despite this overall failure, these trials contributed significantly to increasing knowledge on human leishmaniasis immunology. To provide a collective view, this review discusses the methods and findings of field efficacy trials of first generation leishmaniasis vaccine clinical trials conducted in the Old and New Worlds.

Clinical trials of GMP products in the gene therapy field.

PubMed

Bamford, Kathleen B

2011-01-01

Advances in gene therapy are increasingly leading to clinical assessment in many fields of medicine with diverse approaches. The basic science stems from approaches aimed at different functions such as correcting a missing/abnormal gene, altering the proportion or expression of normal genes to augment a physiological process or using this principle to destroy malignant or infected cells. As the technology advances, it is increasingly important to ensure that clinical trials answer the questions that need to be asked. In this chapter we review examples of published clinical trials, resources for accessing information about registered trials, the process of regulating trials, good clinical practice, and good manufacturing practice as well as summarising the approach taken by regulatory authorities in reviewing applications for the introduction of products for use in the clinic.

Task shifting from doctors to non-doctors for initiation and maintenance of antiretroviral therapy.

PubMed

Kredo, Tamara; Adeniyi, Folasade B; Bateganya, Moses; Pienaar, Elizabeth D

2014-07-01

The high levels of healthcare worker shortage is recognised as a severe impediment to increasing patients' access to antiretroviral therapy. This is particularly of concern where the burden of disease is greatest and the access to trained doctors is limited.This review aims to better inform HIV care programmes that are currently underway, and those planned, by assessing if task-shifting care from doctors to non-doctors provides both high quality and safe care for all patients requiring antiretroviral treatment. To evaluate the quality of initiation and maintenance of HIV/AIDS care in models that task shift care from doctors to non-doctors. We conducted a comprehensive search to identify all relevant studies regardless of language or publication status (published, unpublished, in press, and in progress) from 1 January 1996 to 28 March 2014, with major HIV/AIDS conferences searched 23 May 2014. We had also contacted relevant organizations and researchers. Key words included MeSH terms and free-text terms relevant to 'task shifting', 'skill mix', 'integration of tasks', 'service delivery' and 'health services accessibility'. We included controlled trials (randomised or non-randomised), controlled-before and after studies, and cohort studies (prospective or retrospective) comparing doctor-led antiretroviral therapy delivery to delivery that included another cadre of health worker other than a doctor, for initiating treatment, continuing treatment, or both, in HIV infected patients. Two authors independently screened titles, abstracts and descriptor terms of the results of the electronic search and applied our eligibility criteria using a standardized eligibility form to full texts of potentially eligible or uncertain abstracts. Two reviewers independently extracted data on standardized data extraction forms. Where possible, data were pooled using random effects meta-analysis. We assessed evidence quality with GRADE methodology. Ten studies met our inclusion criteria, all of which were conducted in Africa. Of these four were randomised controlled trials while the remaining six were cohort studies.From the trial data, when nurses initiated and provided follow-up HIV therapy, there was high quality evidence of no difference in death at one year, unadjusted risk ratio was 0.96 (95% CI 0.82 to 1.12), one trial, cluster adjusted n = 2770. There was moderate quality evidence of lower rates of losses to follow-up at one year, relative risk of 0.73 (95% CI 0.55 to 0.97). From the cohort data, there was low quality evidence that there may be an increased risk of death in the task shifting group, relative risk 1.23 (95% CI 1.14 to 1.33, two cohorts, n = 39 160) and very low quality data reporting no difference in patients lost to follow-up between groups, relative risk 0.30 (95% CI 0.05 to 1.94).From the trial data, when doctors initiated therapy and nurses provided follow-up, there was moderate quality evidence that there is probably no difference in death compared with doctor-led care at one year, relative risk of 0.89 (95% CI 0.59 to 1.32), two trials, cluster adjusted n = 4332. There was moderate quality evidence that there is probably no difference in the numbers of patients lost to follow-up at one year, relative risk 1.27 (95% CI 0.92 to 1.77), P = 0.15. From the cohort data, there is very low quality data that death at one year may be lower in the task shifting group, relative risk 0.19 (95% CI 0.05 to 0.78), one cohort, n = 2772, and very low quality evidence that loss to follow-up was reduced, relative risk 0.34 (95% CI 0.18 to 0.66).From the trial data, for maintenance therapy delivered in the community there was moderate quality evidence that there is probably no difference in mortality when doctors deliver care in the hospital or specially trained field workers provide home-based maintenance care and antiretroviral therapy at one year, relative risk 1.0 (95% CI 0.62 to 1.62), 1 trial, cluster adjusted n = 559. There is moderate quality evidence from this trial that losses to follow-up are probably no different at one year, relative risk 0.52 (0.12 to 2.3), P = 0.39. The cohort studies did not report on one year follow-up for these outcomes.Across the studies that reported on virological and immunological outcomes, there was no clear evidence of difference whether a doctor or nurse or clinical officer delivered therapy. Three studies report on costs to patients, indicating a reduction in travel costs to treatment facilities where task shifting was occurring closer to patients homes. There is conflicting evidence regarding the relative cost to the health system, as implementation of the strategy may increase costs. The two studies reporting the patient and staff perceptions of the quality of care, report good acceptability of the service by patients, and general acceptance by doctors of the shifting of roles. One trial reported on the time to initiation of antiretroviral therapy, finding no clear evidence of a difference between groups. The same trial reports on new diagnosis of tuberculosis which favours nurse initiation of HIV care for increasing the numbers of diagnoses of tuberculosis made. Our review found moderate quality evidence that shifting responsibility from doctors to adequately trained and supported nurses or community health workers for managing HIV patients probably does not decrease the quality of care and, in the case of nurse initiated care, may decrease the numbers of patients lost to follow-up.

Clinical trials in crisis: four simple methodologic fixes

PubMed Central

Vickers, Andrew J.

2014-01-01

There is growing consensus that the US clinical trials system is broken, with trial costs and complexity increasing exponentially, and many trials failing to accrue. Yet concerns about the expense and failure rate of randomized trials are only the tip of the iceberg; perhaps what should worry us most is the number of trials that are not even considered because of projected costs and poor accrual. Several initiatives, including the Clinical Trials Transformation Initiative and the “Sensible Guidelines Group” seek to push back against current trends in clinical trials, arguing that all aspects of trials - including design, approval, conduct, monitoring, analysis and dissemination - should be based on evidence rather than contemporary norms. Proposed here are four methodologic fixes for current clinical trials. The first two aim to simplify trials, reducing costs and increasing patient acceptability by dramatically reducing eligibility criteria - often to the single criterion that the consenting physician is uncertain which of the two randomized arms is optimal - and by clinical integration, investment in data infrastructure to bring routinely collected data up to research grade to be used as endpoints in trials. The second two methodologic fixes aim to shed barriers to accrual, either by cluster randomization of clinicians (in the case of modifications to existing treatment) or by early consent, where patients are offered the chance of being randomly selected to be offered a novel intervention if disease progresses at a subsequent point. Such solutions may be partial, or result in a new set of problems of their own. Yet the current crisis in clinical trials mandates innovative approaches: randomized trials have resulted in enormous benefits for patients and we need to ensure that they continue to do so. PMID:25278228

Clinical trials in crisis: Four simple methodologic fixes.

PubMed

Vickers, Andrew J

2014-12-01

There is growing consensus that the US clinical trials system is broken, with trial costs and complexity increasing exponentially, and many trials failing to accrue. Yet, concerns about the expense and failure rate of randomized trials are only the tip of the iceberg; perhaps what should worry us most is the number of trials that are not even considered because of projected costs and poor accrual. Several initiatives, including the Clinical Trials Transformation Initiative and the "Sensible Guidelines Group" seek to push back against current trends in clinical trials, arguing that all aspects of trials-including design, approval, conduct, monitoring, analysis, and dissemination-should be based on evidence rather than contemporary norms. Proposed here are four methodologic fixes for current clinical trials. The first two aim to simplify trials, reducing costs, and increasing patient acceptability by dramatically reducing eligibility criteria-often to the single criterion that the consenting physician is uncertain which of the two randomized arms is optimal-and by clinical integration, investment in data infrastructure to bring routinely collected data up to research grade to be used as endpoints in trials. The second two methodologic fixes aim to shed barriers to accrual, either by cluster randomization of clinicians (in the case of modifications to existing treatment) or by early consent, where patients are offered the chance of being randomly selected to be offered a novel intervention if disease progresses at a subsequent point. Such solutions may be partial, or result in a new set of problems of their own. Yet, the current crisis in clinical trials mandates innovative approaches: randomized trials have resulted in enormous benefits for patients, and we need to ensure that they continue to do so. © The Author(s) 2014.

Rationale, Timeline, Study Design, and Protocol Overview of the Therapeutic Hypothermia After Pediatric Cardiac Arrest Trials

PubMed Central

Moler, Frank W.; Silverstein, Faye S.; Meert, Kathleen L.; Clark, Amy E.; Holubkov, Richard; Browning, Brittan; Slomine, Beth S.; Christensen, James R.; Dean, Michael

2014-01-01

Objective To describe the rationale, timeline, study design, and protocol overview of the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Design Multicenter randomized controlled trials. Setting Pediatric intensive care and cardiac ICUs in the United States and Canada. Patients Children from 48 hours to 18 years old, who have return of circulation after cardiac arrest, who meet trial eligibility criteria, and whose guardians provide written consent. Interventions Therapeutic hypothermia or therapeutic normothermia. Measurements and Main Results From concept inception in 2002 until trial initiation in 2009, 7 years were required to plan and operationalize the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Two National Institute of Child Health and Human Development clinical trial planning grants (R21 and R34) supported feasibility assessment and protocol development. Two clinical research networks, Pediatric Emergency Care Applied Research Network and Collaborative Pediatric Critical Care Research Network, provided infrastructure resources. Two National Heart Lung Blood Institute U01 awards provided funding to conduct separate trials of in-hospital and out-of-hospital cardiac arrest. A pilot vanguard phase that included half the clinical sites began on March 9, 2009, and this was followed by full trial funding through 2015. Conclusions Over a decade will have been required to plan, design, operationalize, and conduct the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Details described in this report, such as participation of clinical research networks and clinical trial planning grants utilization, may be of utility for individuals who are planning investigator-initiated, federally supported clinical trials. PMID:23842585

Impact of the Alzheimer's Disease Neuroimaging Initiative, 2004 to 2014.

PubMed

Weiner, Michael W; Veitch, Dallas P; Aisen, Paul S; Beckett, Laurel A; Cairns, Nigel J; Cedarbaum, Jesse; Donohue, Michael C; Green, Robert C; Harvey, Danielle; Jack, Clifford R; Jagust, William; Morris, John C; Petersen, Ronald C; Saykin, Andrew J; Shaw, Leslie; Thompson, Paul M; Toga, Arthur W; Trojanowski, John Q

2015-07-01

The Alzheimer's Disease Neuroimaging Initiative (ADNI) was established in 2004 to facilitate the development of effective treatments for Alzheimer's disease (AD) by validating biomarkers for AD clinical trials. We searched for ADNI publications using established methods. ADNI has (1) developed standardized biomarkers for use in clinical trial subject selection and as surrogate outcome measures; (2) standardized protocols for use across multiple centers; (3) initiated worldwide ADNI; (4) inspired initiatives investigating traumatic brain injury and post-traumatic stress disorder in military populations, and depression, respectively, as an AD risk factor; (5) acted as a data-sharing model; (6) generated data used in over 600 publications, leading to the identification of novel AD risk alleles, and an understanding of the relationship between biomarkers and AD progression; and (7) inspired other public-private partnerships developing biomarkers for Parkinson's disease and multiple sclerosis. ADNI has made myriad impacts in its first decade. A competitive renewal of the project in 2015 would see the use of newly developed tau imaging ligands, and the continued development of recruitment strategies and outcome measures for clinical trials. Copyright © 2015 The Alzheimer's Association. All rights reserved.

Impact of the Alzheimer’s Disease Neuroimaging Initiative, 2004 to 2014

PubMed Central

Weiner, Michael W.; Veitch, Dallas P.; Aisen, Paul S.; Beckett, Laurel A.; Cairns, Nigel J.; Cedarbaum, Jesse; Donohue, Michael C.; Green, Robert C.; Harvey, Danielle; Jack, Clifford R.; Jagust, William; Morris, John C.; Petersen, Ronald C.; Saykin, Andrew J.; Shaw, Leslie; Thompson, Paul M.; Toga, Arthur W.; Trojanowski, John Q.

2015-01-01

Introduction The Alzheimer’s Disease Neuroimaging Initiative (ADNI) was established in 2004 to facilitate the development of effective treatments for Alzheimer’s disease (AD) by validating biomarkers for AD clinical trials. Methods We searched for ADNI publications using established methods. Results ADNI has (1) developed standardized biomarkers for use in clinical trial subject selection and as surrogate outcome measures; (2) standardized protocols for use across multiple centers; (3) initiated worldwide ADNI; (4) inspired initiatives investigating traumatic brain injury and post-traumatic stress disorder in military populations, and depression, respectively, as an AD risk factor; (5) acted as a data-sharing model; (6) generated data used in over 600 publications, leading to the identification of novel AD risk alleles, and an understanding of the relationship between biomarkers and AD progression; and (7) inspired other public-private partnerships developing biomarkers for Parkinson’s disease and multiple sclerosis. Discussion ADNI has made myriad impacts in its first decade. A competitive renewal of the project in 2015 would see the use of newly developed tau imaging ligands, and the continued development of recruitment strategies and outcome measures for clinical trials. PMID:26194320

The impact of health insurance mandates on drug innovation: evidence from the United States.

PubMed

Chun, Natalie; Park, Minjung

2013-04-01

An important health policy issue is the low rate of patient enrollment into clinical trials, which may slow down the process of clinical trials and discourage their supply, leading to delays in innovative life-saving drug treatments reaching the general population. In the US, patients' cost of participating in a clinical trial is considered to be a major barrier to patient enrollment. In order to reduce this barrier, some states in the US have implemented policies requiring health insurers to cover routine care costs for patients enrolled in clinical trials. This paper evaluates empirically how effective these policies were in increasing the supply of clinical trials and speeding up their completion, using data on cancer clinical trials initiated in the US between 2001 and 2007. Our analysis indicates that the policies did not lead to an increased supply in the number of clinical trials conducted in mandate states compared to non-mandate states. However, we find some evidence that once clinical trials are initiated, they are more likely to finish their patient recruitment in a timely manner in mandate states than in non-mandate states. As a result, the overall length to completion was significantly shorter in mandate states than in non-mandate states for cancer clinical trials in certain phases. The findings hint at the possibility that these policies might encourage drug innovation in the long run.

Mineralocorticoids in the heart and vasculature: new insights for old hormones.

PubMed

Lother, Achim; Moser, Martin; Bode, Christoph; Feldman, Ross D; Hein, Lutz

2015-01-01

The mineralocorticoid aldosterone is a key regulator of water and electrolyte homeostasis. Numerous recent developments have advanced the field of mineralocorticoid pharmacology—namely, clinical trials have shown the beneficial effects of aldosterone antagonists in chronic heart failure and post-myocardial infarction treatment. Experimental studies using cell type-specific gene targeting of the mineralocorticoid receptor (MR) gene in mice have revealed the importance of extrarenal aldosterone signaling in cardiac myocytes, endothelial cells, vascular smooth cells, and macrophages. In addition, several molecular pathways involving signal transduction via the classical MR as well as the G protein-coupled receptor GPER mediate the diverse spectrum of effects of aldosterone on cells. This knowledge has initiated the development of new pharmacological ligands to specifically interfere with targets on different levels of aldosterone signaling. For example, aldosterone synthase inhibitors such as LCI699 and the novel nonsteroidal MR antagonist BAY 94-8862 have been tested in clinical trials. Interference with the interaction between MR and its coregulators seems to be a promising strategy toward the development of selective MR modulators.

Trial Watch: Adoptive cell transfer for oncological indications

PubMed Central

Aranda, Fernando; Buqué, Aitziber; Bloy, Norma; Castoldi, Francesca; Eggermont, Alexander; Cremer, Isabelle; Fridman, Wolf Hervé; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2015-01-01

One particular paradigm of anticancer immunotherapy relies on the administration of (potentially) tumor-reactive immune effector cells. Generally, these cells are obtained from autologous peripheral blood lymphocytes (PBLs) ex vivo (in the context of appropriate expansion, activation and targeting protocols), and re-infused into lymphodepleted patients along with immunostimulatory agents. In spite of the consistent progress achieved throughout the past two decades in this field, no adoptive cell transfer (ACT)-based immunotherapeutic regimen is currently approved by regulatory agencies for use in cancer patients. Nonetheless, the interest of oncologists in ACT-based immunotherapy continues to increase. Accumulating clinical evidence indicates indeed that specific paradigms of ACT, such as the infusion of chimeric antigen receptor (CAR)-expressing autologous T cells, are associated with elevated rates of durable responses in patients affected by various neoplasms. In line with this notion, clinical trials investigating the safety and therapeutic activity of ACT in cancer patients are being initiated at an ever increasing pace. Here, we review recent preclinical and clinical advances in the development of ACT-based immunotherapy for oncological indications. PMID:26451319

Trial Watch: Radioimmunotherapy for oncological indications.

PubMed

Bloy, Norma; Pol, Jonathan; Manic, Gwenola; Vitale, Ilio; Eggermont, Alexander; Galon, Jérôme; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2014-10-01

During the past two decades, it has become increasingly clear that the antineoplastic effects of radiation therapy do not simply reflect the ability of X-, β- and γ-rays to damage transformed cells and directly cause their permanent proliferative arrest or demise, but also involve cancer cell-extrinsic mechanisms. Indeed, among other activities, radiotherapy has been shown to favor the establishment of tumor-specific immune responses that operate systemically, underpinning the so-called 'out-of-field' or 'abscopal' effect. Thus, ionizing rays appear to elicit immunogenic cell death, a functionally peculiar variant of apoptosis associated with the emission of a particularly immunostimulatory combination of damage-associated molecular patterns. In line with this notion, radiation therapy fosters, and thus exacerbates, the antineoplastic effects of various treatment modalities, including surgery, chemotherapy and various immunotherapeutic agents. Here, we summarize recent advances in the use of ionizing rays as a means to induce or potentiate therapeutically relevant anticancer immune responses. In addition, we present clinical trials initiated during the past 12 months to test the actual benefit of radioimmunotherapy in cancer patients.

Escherichia coli O157:H7 vaccine field trial in 9 feedlots in Alberta and Saskatchewan

PubMed Central

2005-01-01

Abstract A feedlot trial was conducted to assess the efficacy of an Escherichia coli O157:H7 vaccine in reducing fecal shedding of E. coli O157:H7 in 218 pens of feedlot cattle in 9 feedlots in Alberta and Saskatchewan. Pens of cattle were vaccinated once at arrival processing and again at reimplanting with either the E. coli O157:H7 vaccine or a placebo. The E. coli O157:H7 vaccine included 50 μg of type III secreted proteins. Fecal samples were collected from 30 fresh manure patties within each feedlot pen at arrival processing, revaccination at reimplanting, and within 2 wk of slaughter. The mean pen prevalence of E. coli O157:H7 in feces was 5.0%; ranging in pens from 0% to 90%, and varying signif icantly (P < 0.001) among feedlots. There was no signif icant association (P > 0.20) between vaccination and pen prevalence of fecal E. coli O157:H7 following initial vaccination, at reimplanting, or prior to slaughter. PMID:16187717

The influence of tyre characteristics on measures of rolling performance during cross-country mountain biking.

PubMed

Macdermid, Paul William; Fink, Philip W; Stannard, Stephen R

2015-01-01

This investigation sets out to assess the effect of five different models of mountain bike tyre on rolling performance over hard-pack mud. Independent characteristics included total weight, volume, tread surface area and tread depth. One male cyclist performed multiple (30) trials of a deceleration field test to assess reliability. Further tests performed on a separate occasion included multiple (15) trials of the deceleration test and six fixed power output hill climb tests for each tyre. The deceleration test proved to be reliable as a means of assessing rolling performance via differences in initial and final speed (coefficient of variation (CV) = 4.52%). Overall differences between tyre performance for both deceleration test (P = 0.014) and hill climb (P = 0.032) were found, enabling significant (P < 0.0001 and P = 0.049) models to be generated, allowing tyre performance prediction based on tyre characteristics. The ideal tyre for rolling and climbing performance on hard-pack surfaces would be to decrease tyre weight by way of reductions in tread surface area and tread depth while keeping volume high.

Trial Watch: Adoptive cell transfer for oncological indications.

PubMed

Aranda, Fernando; Buqué, Aitziber; Bloy, Norma; Castoldi, Francesca; Eggermont, Alexander; Cremer, Isabelle; Fridman, Wolf Hervé; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2015-11-01

One particular paradigm of anticancer immunotherapy relies on the administration of (potentially) tumor-reactive immune effector cells. Generally, these cells are obtained from autologous peripheral blood lymphocytes (PBLs) ex vivo (in the context of appropriate expansion, activation and targeting protocols), and re-infused into lymphodepleted patients along with immunostimulatory agents. In spite of the consistent progress achieved throughout the past two decades in this field, no adoptive cell transfer (ACT)-based immunotherapeutic regimen is currently approved by regulatory agencies for use in cancer patients. Nonetheless, the interest of oncologists in ACT-based immunotherapy continues to increase. Accumulating clinical evidence indicates indeed that specific paradigms of ACT, such as the infusion of chimeric antigen receptor (CAR)-expressing autologous T cells, are associated with elevated rates of durable responses in patients affected by various neoplasms. In line with this notion, clinical trials investigating the safety and therapeutic activity of ACT in cancer patients are being initiated at an ever increasing pace. Here, we review recent preclinical and clinical advances in the development of ACT-based immunotherapy for oncological indications.

Bleomycin--electrical pulse delivery: electroporation therapy-bleomycin--Genetronics; MedPulser-bleomycin--Genetronics.

PubMed

2004-01-01

Genetronics Biomedical is using its electroporation therapy technology to deliver bleomycin to tumour cells for the treatment of cancer. Genetronics have developed the MedPulser Electroporation Therapy System, which consists of an electrical pulse generator and disposable electrode applicators. The MedPulser system enables the delivery of large molecules into cells by briefly applying an electric field to the cell. This causes a transient permeability in the cell's outer membrane characterised by the appearance of pores across the membrane. After the field is discontinued, the pores close, trapping the therapeutic molecules inside the target cells. Genetronics is using the MedPulser System in conjunction with bleomycin, an antineoplastic antibiotic that binds to DNA causing strand scissions. Genetronics is seeking a licensing partner for the use of electroporation for the delivery of drugs in chemotherapy. In 1998, Genetronics entered a licensing and development agreement with Ethicon for electroporation and electrofusion. Under the terms of this agreement, Ethicon was to develop and clinically test the Genetronics electroporation delivery system and conduct all regulatory activities throughout the world except Canada. Ethicon would also market the products once regulatory approval has been obtained and Genetronics was to receive a percentage of the net sales and as license fees. However, in July 2000, Ethicon exercised its rights to terminate the agreement without cause. All rights were returned to Genetronics in January 2001. In 1997, Genetronics entered an agreement with Abbott Laboratories for the manufacture of bleomycin for use in the US in its MedPulsar system after regulatory approval had been granted for its use in the treatment of solid tumours. In a separate supply agreement, Faulding Inc. has agreed to manufacture bleomycin for Genetronic for use in Canada after regulatory approval had been granted. The MedPulsar Electroporation Therapy System with bleomycin is currently in phase III pivotal studies in the US as a treatment for recurrent and second primary squamous cell carcinomas of the head and neck. Genetronics received approval for the Electroporation Therapy system as a device in March 1999 when it achieved CE Mark certification. In February 2004, Genetronics announced that it had completed a Special Protocol Assessment review process with the US FDA for two new trials that will compare bleomycin electroporation therapy to surgery. The primary endpoint will be tissue and function preservation rather than survival. One proposal is for recurrent head and neck cancer, and the other is for disfiguring cutaneous cancer. Three Institutional Review Boards in the US have approved the two protocols and Genetronics has initiated enrollment. In June 2004, Genetronics was granted fast-track status for its MedPulsar Electroporation Therapy System clinical development programme for patients with head and neck cancer. Shifting from a primary endpoint of survival to a quality-of-life outcome will enable those clinical trials to be carried out faster with less cost and with a higher likelihood of success. As a result, Genetronic's phase III trials focussing on survival as a primary endpoint have been discontinued. This includes a phase III trial for late-stage, recurrent head and neck cancer in combination with the normal standard of treatment compared with normal standard of treatment alone. Interim results from this trial had suggested bleomycin electroporation therapy demonstrated local tumour control and preservation of organ function, as well as non-inferiority when compared with surgery. This trial was initiated in May 2002. In March 2004, Genetronics initiated a post-European regulatory approval clinical study in patients with primary or recurrent squamous cell carcinoma of the head and neck (SCCHN). This study aims to enroll approximately 100 patients at 12-15 hospitals located in the UK, Germany, Italy, France, Austria and other western European countries. The study is designed to support the commercialisation of the MedPulser Electroporation System in the EU. Prior clinical trials established the safety and performance of the MedPulser System for the treatment of SCCHN, leading to approval for sale in the EU based on achieving the CE Mark. This study will document the clinical and pharmacoeconomic benefit in support of reimbursement approval throughout Western Europe, establish centres of excellence to facilitate early sales, create a reference and customer base for a projected European commercial launch in 2005, and generate safety and efficacy data to support marketing applications in the US. The bleomycin delivery system has completed phase IIB trials in the US, Canada and Europe in patients with squamous cell carcinoma of the head and neck who have failed conventional therapies. Phase II data were submitted to the FDA in the first quarter of 2002 and a phase III trial was launched in May 2002. The therapy is also being used in France in patients with cancers of the head and neck, liver (metastatic) and melanoma. A review of the data from these phase II trials was completed in April 2001. In June 2004, Genetronics was granted two US patents. US patent 6,748,265 covers its trans-surface drug and gene delivery technology and provides additional proprietary rights for an apparatus and method to deliver genes, drugs and other molecules through tissue surfaces. The second US patent, 6,746,441, pertains to the field of ex vivo therapies and covers the introduction of molecules into cells by electroporation, either in a continuous-flow or batch mode, with a variable electric field orientation. In July 2004, Genetronics received a US patent (no. 6,763,264) covering methods for the in vivo delivery of a recombinant expression vector (DNA) or a pharmaceutical agent into tissue cells, and a method for the therapeutic application of electroporation to a patient to introduce macromolecules. Copyright 2004 Adis Data Information BV

Field trial of a quantum secured 10 Gb/s DWDM transmission system over a single installed fiber.

PubMed

Choi, Iris; Zhou, Yu Rong; Dynes, James F; Yuan, Zhiliang; Klar, Andreas; Sharpe, Andrew; Plews, Alan; Lucamarini, Marco; Radig, Christian; Neubert, Jörg; Griesser, Helmut; Eiselt, Michael; Chunnilall, Christopher; Lepert, Guillaume; Sinclair, Alastair; Elbers, Jörg-Peter; Lord, Andrew; Shields, Andrew

2014-09-22

We present results from the first field-trial of a quantum-secured DWDM transmission system, in which quantum key distribution (QKD) is combined with 4 × 10 Gb/s encrypted data and transmitted simultaneously over 26 km of field installed fiber. QKD is used to frequently refresh the key for AES-256 encryption of the 10 Gb/s data traffic. Scalability to over 40 DWDM channels is analyzed.

Barriers to investigator-initiated deep brain stimulation and device research

PubMed Central

Malone, Donald; Okun, Michael S.; Booth, Joan; Machado, Andre G.

2014-01-01

The success of device-based research in the clinical neurosciences has overshadowed a critical and emerging problem in the biomedical research environment in the United States. Neuroprosthetic devices, such as deep brain stimulation (DBS), have been shown in humans to be promising technologies for scientific exploration of neural pathways and as powerful treatments. Large device companies have, over the past several decades, funded and developed major research programs. However, both the structure of clinical trial funding and the current regulation of device research threaten investigator-initiated efforts in neurologic disorders. The current atmosphere dissuades clinical investigators from pursuing formal and prospective research with novel devices or novel indications. We review our experience in conducting a federally funded, investigator-initiated, device-based clinical trial that utilized DBS for thalamic pain syndrome. We also explore barriers that clinical investigators face in conducting device-based clinical trials, particularly in early-stage studies or small disease populations. We discuss 5 specific areas for potential reform and integration: (1) alternative pathways for device approval; (2) eliminating right of reference requirements; (3) combining federal grant awards with regulatory approval; (4) consolidation of oversight for human subjects research; and (5) private insurance coverage for clinical trials. Careful reformulation of regulatory policy and funding mechanisms is critical for expanding investigator-initiated device research, which has great potential to benefit science, industry, and, most importantly, patients. PMID:24670888

Trial-by-trial adaptation of movements during mental practice under force field.

PubMed

Anwar, Muhammad Nabeel; Khan, Salman Hameed

2013-01-01

Human nervous system tries to minimize the effect of any external perturbing force by bringing modifications in the internal model. These modifications affect the subsequent motor commands generated by the nervous system. Adaptive compensation along with the appropriate modifications of internal model helps in reducing human movement errors. In the current study, we studied how motor imagery influences trial-to-trial learning in a robot-based adaptation task. Two groups of subjects performed reaching movements with or without motor imagery in a velocity-dependent force field. The results show that reaching movements performed with motor imagery have relatively a more focused generalization pattern and a higher learning rate in training direction.

Interventions for promoting the initiation of breastfeeding.

PubMed

Balogun, Olukunmi O; O'Sullivan, Elizabeth J; McFadden, Alison; Ota, Erika; Gavine, Anna; Garner, Christine D; Renfrew, Mary J; MacGillivray, Stephen

2016-11-09

Despite the widely documented risks of not breastfeeding, initiation rates remain relatively low in many high-income countries, particularly among women in lower-income groups. In low- and middle-income countries, many women do not follow World Health Organization (WHO) recommendations to initiate breastfeeding within the first hour after birth. This is an update of a Cochrane Review, first published in 2005. To identify and describe health promotion activities intended to increase the initiation rate of breastfeeding.To evaluate the effectiveness of different types of breastfeeding promotion activities, in terms of changing the number of women who initiate breastfeeding.To evaluate the effectiveness of different types of breastfeeding promotion activities, in terms of changing the number of women who initiate breastfeeding early (within one hour after birth). We searched Cochrane Pregnancy and Childbirth's Trials Register (29 February 2016) and scanned reference lists of all articles obtained. Randomised controlled trials (RCTs), with or without blinding, of any breastfeeding promotion intervention in any population group, except women and infants with a specific health problem. Two review authors independently assessed trial reports for inclusion, extracted data and assessed trial quality. Discrepancies were resolved through discussion and a third review author was involved when necessary. We contacted investigators to obtain missing information. Twenty-eight trials involving 107,362 women in seven countries are included in this updated review. Five studies involving 3,124 women did not contribute outcome data and we excluded them from the analyses. The methodological quality of the included trials was mixed, with significant numbers of studies at high or unclear risk of bias due to: inadequate allocation concealment (N = 20); lack of blinding of outcome assessment (N = 20); incomplete outcome data (N = 19); selective reporting (N = 22) and bias from other potential sources (N = 17). Healthcare professional-led breastfeeding education and support versus standard care The studies pooled here compare professional health workers delivering breastfeeding education and support during the prenatal and postpartum periods with standard care. Interventions included promotion campaigns and counselling, and all took place in a formal setting. There was evidence from five trials involving 564 women for improved rates ofbreastfeeding initiation among women who received healthcare professional-led breastfeeding education and support (average risk ratio (RR) 1.43, 95% confidence interval (CI) 1.07 to 1.92; Tau² = 0.07, I² = 62%, low-quality evidence) compared to those women who received standard care. We downgraded evidence due to design limitations and heterogeneity. The outcome of early initiation of breastfeeding was not reported in the studies under this comparison. Non-healthcare professional-led breastfeeding education and support versus standard care There was evidence from eight trials of 5712 women for improved rates of breastfeeding initiation among women who received interventions from non-healthcare professional counsellors and support groups (average RR 1.22, 95% CI 1.06 to 1.40; Tau² = 0.02, I² = 86%, low-quality evidence) compared to women who received standard care. In three trials of 76,373 women, there was no clear difference between groups in terms of the number of women practicing early initiation of breastfeeding (average RR 1.70, 95% CI 0.98 to 2.95; Tau² = 0.18, I² = 78%, very low-quality evidence). We downgraded the evidence for a combination of design limitations, heterogeneity and imprecision (wide confidence intervals crossing the line of no effect). Other comparisonsOther comparisons in this review also looked at the rates of initiation of breastfeeding and there were no clear differences between groups for the following comparisons of combined healthcare professional-led education with peer support or community educator versus standard care (2 studies, 1371 women) or attention control (1 study, 237 women), breastfeeding education using multimedia (a self-help manual or a video) versus routine care (2 studies, 497 women); early mother-infant contact versus standard care (2 studies, 309 women); and community-based breastfeeding groups versus no breastfeeding groups (1 study, 18,603 women). None of these comparisons reported data on early initiation of breastfeeding. This review found low-quality evidence that healthcare professional-led breastfeeding education and non-healthcare professional-led counselling and peer support interventions can result in some improvements in the number of women beginning to breastfeed. The majority of the trials were conducted in the USA, among women on low incomes and who varied in ethnicity and feeding intention, thus limiting the generalisability of these results to other settings.Future studies would ideally be conducted in a range of low- and high-income settings, with data on breastfeeding rates over various timeframes, and explore the effectiveness of interventions that are initiated prior to conception or during pregnancy. These might include well-described interventions, including health education, early and continuing mother-infant contact, and initiatives to help mothers overcome societal barriers to breastfeeding, all with clearly defined outcome measures.

In pursuit of a science of agriculture: the role of statistics in field experiments.

PubMed

Parolini, Giuditta

2015-09-01

Since the beginning of the twentieth century statistics has reshaped the experimental cultures of agricultural research taking part in the subtle dialectic between the epistemic and the material that is proper to experimental systems. This transformation has become especially relevant in field trials and the paper will examine the British agricultural institution, Rothamsted Experimental Station, where statistical methods nowadays popular in the planning and analysis of field experiments were developed in the 1920s. At Rothamsted statistics promoted randomisation over systematic arrangements, factorisation over one-question trials, and emphasised the importance of the experimental error in assessing field trials. These changes in methodology transformed also the material culture of agricultural science, and a new body, the Field Plots Committee, was created to manage the field research of the agricultural institution. Although successful, the vision of field experimentation proposed by the Rothamsted statisticians was not unproblematic. Experimental scientists closely linked to the farming community questioned it in favour of a field research that could be more easily understood by farmers. The clash between the two agendas reveals how the role attributed to statistics in field experimentation defined different pursuits of agricultural research, alternately conceived of as a scientists' science or as a farmers' science.

When Wait Lists Are Not Feasible, Nothing Is a Thing That Does Not Need to Be Done

ERIC Educational Resources Information Center

Devilly, Grant J.; McFarlane, Alexander C.

2009-01-01

Clinical psychology practices initially grew through the use of case studies, uncontrolled trials, and eventually through randomized controlled trials (RCTs). The use of a wait-list control group is standard practice in such trials of treatment regimens for psychopathological conditions. However, as knowledge advances regarding the successful…

About the Community Oncology and Prevention Trials Research Group | Division of Cancer Prevention

Cancer.gov

The Community Oncology and Prevention Trials Research Group supports clinical oncology trials in cancer prevention and control in community settings. The group also supports investigator-initiated research projects in supportive, palliative and end-of-life care, and coordinates clinical oncology research projects with other NCI programs to be done in the community setting. |

Role of neonicotinyl insecticides in Washington apple integrated pest management. Part I. Control of lepidopteran pests

PubMed Central

Brunner, J. F.; Beers, E. H.; Dunley, J. E.; Doerr, M.; Granger, K.

2005-01-01

Three neonicotinyl insecticides, acetamiprid, thiacloprid and clothianidin, were evaluated for their impact on four species of lepidopteran pests of apple in Washington, the codling moth, Cydia pomonella (L.), the Pandemis leafroller, Pandemis pyrusana Kearfott, and the obliquebanded leafroller, Choristoneura rosaceana (Harris), and Lacanobia subjuncta (Grote & Robinson). None of the neonicotinyl insecticides demonstrated sufficient activity against P. pyrusana, C. rosaceana, or L. subjuncta to warrant field trials. Conversely, all had some activity against one or more stages of C. pomonella. Acetamiprid was highly toxic to larvae in laboratory bioassays, and had relatively long activity of field-aged residues (21 days). It also showed some toxicity to C. pomonella eggs (via topical exposure) and adults. Acetamiprid provided the highest level of fruit protection from C. pomonella attack in field trials conducted over five years in experimental orchards with extremely high codling moth pressure. Thiacloprid performed similarly in bioassays, but fruit protection in field trials was slightly lower than acetamiprid. Clothianidin showed moderate to high toxicity in bioassays, depending on the C. pomonella stage tested, but poor fruit protection from attack in field trials. None of the neonicotinyl insecticides were as toxic to larvae or effective in protecting fruit as the current standard organophosphate insecticide used for C. pomonella control, azinphosmethyl. However, both acetamiprid and thiacloprid should provide acceptable levels of C. pomonella control in commercial orchards where densities are much lower than in the experimental orchards used for our trials. The advantages and disadvantages of the neonicotinyl insecticides as replacements for the organophosphate insecticides and their role in a pest management system for Washington apple orchards are discussed. Abbreviation: MFR Maximum field rate PMID:16341246

Methods to Prove 20+ Year Life of CPV Products (in less than 20 Years)

NASA Astrophysics Data System (ADS)

Bowman, John; Spencer, Mark

2011-12-01

Due to the long term life expectations of photovoltaic products and the short duration of most introduced CPV technologies, it is critical for CPV companies to carefully construct field trials to prove product life. Because of the complicated geometric, thermal, and spectral characteristics of CPV systems, conducting very precise power output measurements reproducibly over many months is very difficult. Robust normalization methods specific to the exact optical system and PV cell type must be developed. Once the performance over a specific duration, e.g. one year, is established, then some justification is required to extrapolate to future performance. Comparisons to accelerated test results provide this justification. SolFocus has been conducting field trials of the SF-1100S CPV system for over two years. These field trials consist of controlled populations of SF-1100P modules, operating in grid-tied systems, which have been repeatedly measured at the individual module level over the duration of the trials. In this paper, field data will be presented along with normalization methodology and statistical methods for determining power degradation slope distributions for populations of individual modules. These results will be correlated with accelerated field tests which have been ongoing for 1.5 years and are estimated to be equivalent to 10 to 15 years of non-accelerated operation.

Rehabilitation for distal radial fractures in adults.

PubMed

Handoll, Helen H G; Elliott, Joanne

2015-09-25

Fracture of the distal radius is a common clinical problem, particularly in older people with osteoporosis. There is considerable variation in the management, including rehabilitation, of these fractures. This is an update of a Cochrane review first published in 2002 and last updated in 2006. To examine the effects of rehabilitation interventions in adults with conservatively or surgically treated distal radial fractures. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2014; Issue 12), MEDLINE, EMBASE, CINAHL, AMED, PEDro, OTseeker and other databases, trial registers, conference proceedings and reference lists of articles. We did not apply any language restrictions. The date of the last search was 12 January 2015. Randomised controlled trials (RCTs) or quasi-RCTs evaluating rehabilitation as part of the management of fractures of the distal radius sustained by adults. Rehabilitation interventions such as active and passive mobilisation exercises, and training for activities of daily living, could be used on their own or in combination, and be applied in various ways by various clinicians. The review authors independently screened and selected trials, and reviewed eligible trials. We contacted study authors for additional information. We did not pool data. We included 26 trials, involving 1269 mainly female and older patients. With few exceptions, these studies did not include people with serious fracture or treatment-related complications, or older people with comorbidities and poor overall function that would have precluded trial participation or required more intensive treatment. Only four of the 23 comparisons covered by these 26 trials were evaluated by more than one trial. Participants of 15 trials were initially treated conservatively, involving plaster cast immobilisation. Initial treatment was surgery (external fixation or internal fixation) for all participants in five trials. Initial treatment was either surgery or plaster cast alone in six trials. Rehabilitation started during immobilisation in seven trials and after post-immobilisation in the other 19 trials. As well as being small, the majority of the included trials had methodological shortcomings and were at high risk of bias, usually related to lack of blinding, that could affect the validity of their findings. Based on GRADE criteria for assessment quality, we rated the evidence for each of the 23 comparisons as either low or very low quality; both ratings indicate considerable uncertainty in the findings.For interventions started during immobilisation, there was very low quality evidence of improved hand function for hand therapy compared with instructions only at four days after plaster cast removal, with some beneficial effects continuing one month later (one trial, 17 participants). There was very low quality evidence of improved hand function in the short-term, but not in the longer-term (three months), for early occupational therapy (one trial, 40 participants), and of a lack of differences in outcome between supervised and unsupervised exercises (one trial, 96 participants).Four trials separately provided very low quality evidence of clinically marginal benefits of specific interventions applied in addition to standard care (therapist-applied programme of digit mobilisation during external fixation (22 participants); pulsed electromagnetic field (PEMF) during cast immobilisation (60 participants); cyclic pneumatic soft tissue compression using an inflatable cuff placed under the plaster cast (19 participants); and cross-education involving strength training of the non-fractured hand during cast immobilisation with or without surgical repair (39 participants)).For interventions started post-immobilisation, there was very low quality evidence from one study (47 participants) of improved function for a single session of physiotherapy, primarily advice and instructions for a home exercise programme, compared with 'no intervention' after cast removal. There was low quality evidence from four heterogeneous trials (30, 33, 66 and 75 participants) of a lack of clinically important differences in outcome in patients receiving routine physiotherapy or occupational therapy in addition to instructions for home exercises versus instructions for home exercises from a therapist. There was very low quality evidence of better short-term hand function in participants given physiotherapy than in those given either instructions for home exercises by a surgeon (16 participants, one trial) or a progressive home exercise programme (20 participants, one trial). Both trials (46 and 76 participants) comparing physiotherapy or occupational therapy versus a progressive home exercise programme after volar plate fixation provided low quality evidence in favour of a structured programme of home exercises preceded by instructions or coaching. One trial (63 participants) provided very low quality evidence of a short-term, but not persisting, benefit of accelerated compared with usual rehabilitation after volar plate fixation.For trials testing single interventions applied post-immobilisation, there was very low quality evidence of no clinically significant differences in outcome in patients receiving passive mobilisation (69 participants, two trials), ice (83 participants, one trial), PEMF (83 participants, one trial), PEMF plus ice (39 participants, one trial), whirlpool immersion (24 participants, one trial), and dynamic extension splint for patients with wrist contracture (40 participants, one trial), compared with no intervention. This finding applied also to the trial (44 participants) comparing PEMF versus ice, and the trial (29 participants) comparing manual oedema mobilisation versus traditional oedema treatment. There was very low quality evidence from single trials of a short-term benefit of continuous passive motion post-external fixation (seven participants), intermittent pneumatic compression (31 participants) and ultrasound (38 participants). The available evidence from RCTs is insufficient to establish the relative effectiveness of the various interventions used in the rehabilitation of adults with fractures of the distal radius. Further randomised trials are warranted. However, in order to optimise research effort and engender the large multicentre randomised trials that are required to inform practice, these should be preceded by research that aims to identify priority questions.

Mindfulness Training and Reductions in Teacher Stress and Burnout: Results from Two Randomized, Waitlist-Control Field Trials

ERIC Educational Resources Information Center

Roeser, Robert W.; Schonert-Reichl, Kimberly A.; Jha, Amishi; Cullen, Margaret; Wallace, Linda; Wilensky, Rona; Oberle, Eva; Thomson, Kimberly; Taylor, Cynthia; Harrison, Jessica

2013-01-01

The effects of randomization to mindfulness training (MT) or to a waitlist-control condition on psychological and physiological indicators of teachers' occupational stress and burnout were examined in 2 field trials. The sample included 113 elementary and secondary school teachers (89% female) from Canada and the United States. Measures were…

Cucumber cultivars for container gardening and the value of field trials for predicting Cucumber performance in containers

USDA-ARS?s Scientific Manuscript database

Cucumber (Cucumis sativus L.) is one of the most popular vegetable crops grown in U.S. home and urban gardens. The objectives of this study were to identify cultivars and planting densities for high yield of container-grown cucumbers. Additional objectives were to determine the value of field trials...

A Multisite Cluster Randomized Field Trial of Open Court Reading

ERIC Educational Resources Information Center

Borman, Geoffrey D.; Dowling, N. Maritza; Schneck, Carrie

2008-01-01

In this article, the authors report achievement outcomes of a multisite cluster randomized field trial of Open Court Reading 2005 (OCR), a K-6 literacy curriculum published by SRA/McGraw-Hill. The participants are 49 first-grade through fifth-grade classrooms from predominantly minority and poor contexts across the nation. Blocking by grade level…

[Microdose clinical trial--impact of PET molecular imaging].

PubMed

Yano, Tsuneo; Watanabe, Yasuyoshi

2010-10-01

Microdose (MD) clinical trial and exploratory IND study including sub-therapeutic dose and therapeutic dose which are higher than microdoses are expected to bring about innovations in drug development. The outlines of guidances for microdose clinical trial and ICH-M3 (R2) issued by the MHLW in June, 2008, and February, 2010, are first explained, respectively, and some examples of their application to clinical developments of therapeutic drugs in the infection and cancer fields are introduced. Especially, thanks to the progress of molecular imaging research, a new field of drug development is explored by using imaging biomarkers for efficacy or safety evaluation which visualize biomarkers by PET imaging agents. Finally, the roadmap for drug development in infection and cancer fields utilizing PET molecular imaging is discussed.

Economic burden of clinical trials in lung cancer in a German Comprehensive Cancer Center.

PubMed

Kron, F; Kostenko, A; Scheffler, M; Müller, D; Glossmann, J-P; Fischer, R; Michels, S; Nogova, L; Hallek, M; Zander, T; Wolf, J

2017-06-01

The recent success of individualized lung cancer therapy has triggered fundamental changes in clinical research strategies. To date there is a strong focus on early proof of concept trials in genetically preselected small patient subgroups. This analysis focuses on the economic burden caused by such trials for advanced lung cancer patients in a German Comprehensive Cancer Center (CCC). The profit margins between recruiting groups with ≤3 and >3 patients were compared. Clinical and economic data from clinical trials for advanced lung cancer (LC), pharma-sponsored trials (PhST) as well as investigator initiated trials (IIT), conducted between 2011 and 2015 at the Center for Integrated Oncology (CIO) Cologne, were analyzed using a profit-center calculation model. 161 patients were enrolled in 27 clinical trials. The key economic parameter determining costs and payments was the 'trial visits'. In comparison of the two groups (A≤3; B>3 patients enrolled) we found negative profit margins for the low recruiting group (€ -1444). Concerning the number of visits significant differences were found between PhST and IIT (p=0.009). Additionally, sub-analysis show structural differences in cost composition by conducting PhST and IIT. Trials with low patient numbers and IIT, do not cover the cost. To ensure adequate, cost-covering compensation by pharmaceutical companies CCCs have to thoroughly calculate the cost of early proof of concept trials. The findings of this study also underline the need for novel structures in public funding for investigator-initiated clinical trials in precision medicine. Copyright © 2017 Elsevier B.V. All rights reserved.

Cost-effective FITL technologies for small business and residential customers

NASA Astrophysics Data System (ADS)

Andersen, Niels E.; Woolnough, Peter; Seidenberg, Juergen; Ferreira, Mario F. S.

1995-02-01

FIRST is a RACE project where 5 main European telecoms operators, 4 equipment manufacturers and one university have joined up to define and test in a field trial in Portugal a cost effective Optical Access Network. The main design target has been a system which gives cost effective provision of wideband services for small and medium business customers. The system however, incorporates provision of telephone, ISDN and analog and digital video for residential customers as well. Technologies have been chosen with the objective of providing a simple, robust and flexible system where initial deployment costs are low and closely related to the service take up. The paper describes the main technical features of the system and network applications which shows how the system may be introduced in network planning. The system is based on Passive Optical Network technology where video is distributed in the 1550 nm window and telecoms services transmitted at 1300 nm in full duplex mode. The telecoms system provides high capacity, flexibility in loop length and robustness towards outside plant performance. The Subcarrier Multiple Access (SCMA) method is used for upstream transmission of bi-directional telecoms services. SCMA has advantages compared to the Time Division Multiple Access technology used in other systems. Bandwidth/cost tradeoff is better and the lower requirements to the outside plant increases the overall cost benefit. Optical beat noise due to overlapping of laser spectra which may be a problem for this technology has been addressed with success through the use of a suitable modulation and control technique. This technology is further validated in the field trial. The video system provides cost effective long distance transmission on standard fiber with externally modulated lasers and cascaded amplifiers. Coexistence of analog and digital video on one fiber with different modulation schemes i.e. BPSK, QPSK and 64 QAM have been validated. Total life cycle cost evaluations based on availability data, maintenance requirements and expectations for service development have been made. The field trial will be running for two years.

Early Surgery versus Initial Conservative Treatment in Patients with Traumatic Intracerebral Hemorrhage (STITCH[Trauma]): The First Randomized Trial

PubMed Central

Mendelow, A. David; Rowan, Elise N.; Francis, Richard; McColl, Elaine; McNamee, Paul; Chambers, Iain R.; Unterberg, Andreas; Boyers, Dwayne; Mitchell, Patrick M.

2015-01-01

Abstract Intraparenchymal hemorrhages occur in a proportion of severe traumatic brain injury TBI patients, but the role of surgery in their treatment is unclear. This international multi-center, patient-randomized, parallel-group trial compared early surgery (hematoma evacuation within 12 h of randomization) with initial conservative treatment (subsequent evacuation allowed if deemed necessary). Patients were randomized using an independent randomization service within 48 h of TBI. Patients were eligible if they had no more than two intraparenchymal hemorrhages of 10 mL or more and did not have an extradural or subdural hematoma that required surgery. The primary outcome measure was the traditional dichotomous split of the Glasgow Outcome Scale obtained by postal questionnaires sent directly to patients at 6 months. The trial was halted early by the UK funding agency (NIHR HTA) for failure to recruit sufficient patients from the UK (trial registration: ISRCTN19321911). A total of 170 patients were randomized from 31 of 59 registered centers worldwide. Of 82 patients randomized to early surgery with complete follow-up, 30 (37%) had an unfavorable outcome. Of 85 patients randomized to initial conservative treatment with complete follow-up, 40 (47%) had an unfavorable outcome (odds ratio, 0.65; 95% confidence interval, CI 0.35, 1.21; p=0.17), with an absolute benefit of 10.5% (CI, −4.4–25.3%). There were significantly more deaths in the first 6 months in the initial conservative treatment group (33% vs. 15%; p=0.006). The 10.5% absolute benefit with early surgery was consistent with the initial power calculation. However, with the low sample size resulting from the premature termination, we cannot exclude the possibility that this could be a chance finding. A further trial is required urgently to assess whether this encouraging signal can be confirmed. PMID:25738794

Different methods of image segmentation in the process of meat marbling evaluation

NASA Astrophysics Data System (ADS)

Ludwiczak, A.; Ślósarz, P.; Lisiak, D.; Przybylak, A.; Boniecki, P.; Stanisz, M.; Koszela, K.; Zaborowicz, M.; Przybył, K.; Wojcieszak, D.; Janczak, D.; Bykowska, M.

2015-07-01

The level of marbling in meat assessment based on digital images is very popular, as computer vision tools are becoming more and more advanced. However considering muscle cross sections as the data source for marbling level evaluation, there are still a few problems to cope with. There is a need for an accurate method which would facilitate this evaluation procedure and increase its accuracy. The presented research was conducted in order to compare the effect of different image segmentation tools considering their usefulness in meat marbling evaluation on the muscle anatomical cross - sections. However this study is considered to be an initial trial in the presented field of research and an introduction to ultrasonic images processing and analysis.

The Oklahoma City bombing: the roles of the dental teams ... and the lessons learned.

PubMed

Glass, R T

1998-01-01

The Oklahoma City bombing is considered by most historians the worst act of domestic terrorism ever to have occurred in the United States. The response to the disaster, however, is considered by most experts in the field as being the best; creating what is known as the "Oklahoma Standard". The roles of the dental teams in the resolution were pivotal and until now, the recognition of these roles have not been described, due to this being considered a case of mass murder. The purpose of this paper is to give an overview of the preparations, the initial responses, the roles of the dental teams in the resolution, the preparations for the criminal trials, and some of the lessons that were learned.

IMBLMS phase B4, additional tasks 5.0. Microbial identification system

NASA Technical Reports Server (NTRS)

1971-01-01

A laboratory study was undertaken to provide simplified procedures leading to the presumptive identification (I/D) of defined microorganisms on-board an orbiting spacecraft. Identifications were to be initiated by nonprofessional bacteriologists, (crew members) on a contingency basis only. Key objectives/constraints for this investigation were as follows:(1) I/D procedures based on limited, defined diagnostic tests, (2) testing oriented about ten selected microorganisms, (3) provide for definitive I/D key and procedures per selected organism, (4) define possible occurrences of false positives for the resulting I/D key by search of the appropriate literature, and (5) evaluation of the I/D key and procedure through a limited field trial on randomly selected subjects using the I/D key.

Zebrafish models for functional and toxicological screening of nanoscale drug delivery systems: promoting preclinical applications

PubMed Central

Lee, Keon Yong; Jang, Gun Hyuk; Byun, Cho Hyun; Jeun, Minhong

2017-01-01

Preclinical screening with animal models is an important initial step in clinical translation of new drug delivery systems. However, establishing efficacy, biodistribution, and biotoxicity of complex, multicomponent systems in small animal models can be expensive and time-consuming. Zebrafish models represent an alternative for preclinical studies for nanoscale drug delivery systems. These models allow easy optical imaging, large sample size, and organ-specific studies, and hence an increasing number of preclinical studies are employing zebrafish models. In this review, we introduce various models and discuss recent studies of nanoscale drug delivery systems in zebrafish models. Also in the end, we proposed a guideline for the preclinical trials to accelerate the progress in this field. PMID:28515222

Blending research and practice: an evolving dissemination strategy in substance abuse.

PubMed

Michel, Mary Ellen; Pintello, Denise A; Subramaniam, Geetha

2013-01-01

Substance abuse is a leading cause of death and disability throughout the world. The mission of the National Institute on Drug Abuse (NIDA) is to lead the United States in bringing the power of science to bear on drug abuse and addiction. This charge has two critical components: (a) strategic support of research across a broad range of disciplines and (b) rapid, effective dissemination of research results that can improve prevention and treatment efforts, with potential to inform policy. The NIDA Clinical Trials Network and the Blending Initiative are critical elements of this strategy, and the social work field is poised to use these resources to expand its role in the dissemination and implementation of NIDA's mission.

Trial Watch: Immunotherapy plus radiation therapy for oncological indications.

PubMed

Vacchelli, Erika; Bloy, Norma; Aranda, Fernando; Buqué, Aitziber; Cremer, Isabelle; Demaria, Sandra; Eggermont, Alexander; Formenti, Silvia Chiara; Fridman, Wolf Hervé; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2016-01-01

Malignant cells succumbing to some forms of radiation therapy are particularly immunogenic and hence can initiate a therapeutically relevant adaptive immune response. This reflects the intrinsic antigenicity of malignant cells (which often synthesize a high number of potentially reactive neo-antigens) coupled with the ability of radiation therapy to boost the adjuvanticity of cell death as it stimulates the release of endogenous adjuvants from dying cells. Thus, radiation therapy has been intensively investigated for its capacity to improve the therapeutic profile of several anticancer immunotherapies, including (but not limited to) checkpoint blockers, anticancer vaccines, oncolytic viruses, Toll-like receptor (TLR) agonists, cytokines, and several small molecules with immunostimulatory effects. Here, we summarize recent preclinical and clinical advances in this field of investigation.

Zebrafish models for functional and toxicological screening of nanoscale drug delivery systems: promoting preclinical applications.

PubMed

Lee, Keon Yong; Jang, Gun Hyuk; Byun, Cho Hyun; Jeun, Minhong; Searson, Peter C; Lee, Kwan Hyi

2017-06-30

Preclinical screening with animal models is an important initial step in clinical translation of new drug delivery systems. However, establishing efficacy, biodistribution, and biotoxicity of complex, multicomponent systems in small animal models can be expensive and time-consuming. Zebrafish models represent an alternative for preclinical studies for nanoscale drug delivery systems. These models allow easy optical imaging, large sample size, and organ-specific studies, and hence an increasing number of preclinical studies are employing zebrafish models. In this review, we introduce various models and discuss recent studies of nanoscale drug delivery systems in zebrafish models. Also in the end, we proposed a guideline for the preclinical trials to accelerate the progress in this field. © 2017 The Author(s).

Clinical Development of a Cytomegalovirus DNA Vaccine: From Product Concept to Pivotal Phase 3 Trial.

PubMed

Smith, Larry R; Wloch, Mary K; Chaplin, Jennifer A; Gerber, Michele; Rolland, Alain P

2013-09-25

2013 marks a milestone year for plasmid DNA vaccine development as a first-in-class cytomegalovirus (CMV) DNA vaccine enters pivotal phase 3 testing. This vaccine consists of two plasmids expressing CMV antigens glycoprotein B (gB) and phosphoprotein 65 (pp65) formulated with a CRL1005 poloxamer and benzalkonium chloride (BAK) delivery system designed to enhance plasmid expression. The vaccine's planned initial indication under investigation is for prevention of CMV reactivation in CMV-seropositive (CMV⁺) recipients of an allogeneic hematopoietic stem cell transplant (HCT). A randomized, double-blind placebo-controlled phase 2 proof-of-concept study provided initial evidence of the safety of this product in CMV⁺ HCT recipients who underwent immune ablation conditioning regimens. This study revealed a significant reduction in viral load endpoints and increased frequencies of pp65-specific interferon-γ-producing T cells in vaccine recipients compared to placebo recipients. The results of this endpoint-defining trial provided the basis for defining the primary and secondary endpoints of a global phase 3 trial in HCT recipients. A case study is presented here describing the development history of this vaccine from product concept to initiation of the phase 3 trial.

A History of Streptokinase Use in Acute Myocardial Infarction

PubMed Central

Sikri, Nikhil; Bardia, Amit

2007-01-01

A serendipitous discovery by William Smith Tillett in 1933, followed by many years of work with his student Sol Sherry, laid a sound foundation for the use of streptokinase as a thrombolytic agent in the treatment of acute myocardial infarction. The drug found initial clinical application in combating fibrinous pleural exudates, hemothorax, and tuberculous meningitis. In 1958, Sherry and others started using streptokinase in patients with acute myocardial infarction and changed the focus of treatment from palliation to “cure.” Initial trials that used streptokinase infusion produced conflicting results. An innovative approach of intracoronary streptokinase infusion was initiated by Rentrop and colleagues in 1979. Subsequently, larger trials of intracoronary infusion achieved reperfusion rates ranging from 70% to 90%. The need for a meticulously planned and systematically executed randomized multicenter trial was fulfilled by the Gruppo Italiano per la Sperimentazione della Streptochinasi nell'Infarto Miocardico (GISSI) trial in 1986, which not only validated streptokinase as an effective therapeutic method but also established a fixed protocol for its use in acute myocardial infarction. Currently, despite the wide use of tissue plasminogen activator in developed nations, streptokinase remains essential to the management of acute myocardial infarction in developing nations. PMID:17948083

TREATMENT OF LEAD EXPOSED CHILDREN TRIAL

EPA Science Inventory

The Treatment of Lead-exposed Children (TLC) clinical trial compared the effect of lead chelation with succimer to placebo therapy. Outcomes included IQ, neuropsychological function, behavior, physical growth and blood pressure three years after initiation of treatment. Residenti...

Initial Readability Assessment of Clinical Trial Eligibility Criteria

PubMed Central

Kang, Tian; Elhadad, Noémie; Weng, Chunhua

2015-01-01

Various search engines are available to clinical trial seekers. However, it remains unknown how comprehensible clinical trial eligibility criteria used for recruitment are to a lay audience. This study initially investigated this problem. Readability of eligibility criteria was assessed according to (i) shallow and lexical characteristics through the use of an established, generic readability metric; (ii) syntactic characteristics through natural language processing techniques; and (iii) health terminological characteristics through an automated comparison to technical and lay health texts. We further stratified clinical trials according to various study characteristics (e.g., source country or study type) to understand potential factors influencing readability. Mainly caused by frequent use of technical jargons, a college reading level was found to be necessary to understand eligibility criteria text, a level much higher than the average literacy level of the general American population. The use of technical jargons should be minimized to simplify eligibility criteria text. PMID:26958204

Innovative strategies for early clinical R&D.

PubMed

Butz, Robert F; Morelli, Gaetano

2008-01-01

Developments in translational medicine and regulatory initiatives associated with the FDA's Critical Path Initiative are creating new opportunities for innovation in early clinical R&D. The introduction of the exploratory IND process allows small, 'phase 0' clinical trials to be conducted prior to traditional phase I trials - sometimes requiring considerably less chemistry, manufacturing and controls, or preclinical support. Phase 0 clinical trials involving subtherapeutic, yet pharmacologically active, dose levels can provide an early demonstration of clinical proof of concept; such demonstration is of particular importance to small pharmaceutical and early-stage biotechnology companies. However, these opportunities for rapid entry into the clinic must be balanced by a consideration of the unique risks associated with first-in-human clinical trials, and by accounting for public concerns regarding drug safety in general. This feature review discusses how innovative clinical strategies can be used effectively in early drug development.

Taking Working Memory Training from the Laboratory into Schools

ERIC Educational Resources Information Center

Holmes, Joni; Gathercole, Susan Elizabeth

2014-01-01

Working memory skills have been shown to be enhanced by adaptive training in several randomised controlled trials. Here, two field trials were conducted in which teachers administered working memory training to their own pupils in school. Twenty-two children aged 8-9?years participated in Trial 1. In Trial 2, 50 children aged 9-11?years with the…

Stem Cell Trials for Cardiovascular Medicine: Ethical Rationale

PubMed Central

Teraa, Martin; Hesam, Husna; van Delden, Johannes J.M.; Verhaar, Marianne C.; Bredenoord, Annelien L.

2014-01-01

Stem cell-based interventions provide new treatment prospects for many disease conditions, including cardiovascular disorders. Clinical trials are necessary to collect adequate evidence on (long-term) safety and efficacy of novel interventions such as stem cells, but the design and launch of clinical trials, from first-in-human studies to larger randomized controlled trials (RCTs), is scientifically and ethically challenging. Stem cells are different from traditional pharmaceuticals, surgical procedures, and medical devices in the following ways: the novelty and complexity of stem cells, the invasiveness of the procedures, and the novel aim of regeneration. These specifics, combined with the characteristics of the study population, will have an impact on the design and ethics of RCTs. The recently closed JUVENTAS trial will serve as an example to identify the (interwoven) scientific and ethical challenges in the design and launch of stem cell RCTs. The JUVENTAS trial has investigated the efficacy of autologous bone marrow cells in end-stage vascular patients, in a double-blind sham-controlled design. We first describe the choices, considerations, and experiences of the JUVENTAS team. Subsequently, we identify the main ethical and scientific challenges and discuss what is important to consider in the design of future stem cell RCTs: assessment of risks and benefits, the choice for outcome measures, the choice for the comparator, the appropriate selection of participants, and adequate informed consent. Additionally, the stem cell field is highly in the spotlight due to the (commercial) interests and expectations. This warrants a cautious pace of translation and scrupulous set up of clinical trials, as failures could put the field in a negative light. At the same time, knowledge from clinical trials is necessary for the field to progress. We conclude that in the scientifically and ethically challenging field of stem cell RCTs, researchers and clinicians have to maneuver between the Skylla of hyper accelerated translation without rigorously conducted RCTs and the Charybdis of the missed opportunity of valuable knowledge. PMID:24164351

Effect of Breastfeeding Promotion on Early Childhood Caries and Breastfeeding Duration among 5 Year Old Children in Eastern Uganda: A Cluster Randomized Trial.

PubMed

Birungi, Nancy; Fadnes, Lars T; Okullo, Isaac; Kasangaki, Arabat; Nankabirwa, Victoria; Ndeezi, Grace; Tumwine, James K; Tylleskär, Thorkild; Lie, Stein Atle; Åstrøm, Anne Nordrehaug

2015-01-01

Although several studies have shown short term health benefits of exclusive breastfeeding (EBF), its long term consequences have not been studied extensively in low-income contexts. This study assessed the impact of an EBF promotion initiative for 6 months on early childhood caries (ECC) and breastfeeding duration in children aged 5 years in Mbale, Eastern Uganda. Participants were recruited from the Ugandan site of the PROMISE- EBF cluster randomised trial (ClinicalTrials.gov no: NCT00397150). A total of 765 pregnant women from 24 clusters were included in the ratio 1:1 to receive peer counselled promotion of EBF as the intervention or standard of care. At the 5 year follow-up, ECC was recorded under field conditions using the World Health Organization's decayed missing filled tooth (dmft) index. Adjusted negative binomial and linear regression were used in the analysis. Mean breastfeeding duration in the intervention and control groups (n=417) were 21.8 (CI 20.7-22.9) and 21.3(CI 20.7-21.9) months, respectively. The mean dmft was 1.5 (standard deviation [SD] 2.9) and 1.7 (SD 2.9) in the intervention and control groups, respectively. Corresponding prevalence estimates of ECC were 38% and 41%. Negative binomial regression analysis adjusted for cluster effects and loss-to-follow-up by inverse probability weights (IPW) showed an incidence-rate ratio (IRR) of 0.91 (95% CI 0.65-1.2). Comparing the effect of the trial arm on breastfeeding duration showed a difference in months of 0.48 (-0.72 to 1.7). PROMISE EBF trial did not impact on early childhood caries or breastfeeding duration at 5 years of age. This study contributes to the body of evidence that promotion of exclusive breastfeeding does not raise oral health concerns. However, the high burden of caries calls for efforts to improve the oral health condition in this setting. ClinicalTrials.gov NCT00397150.

Clinical use of vaginal or rectally applied microbicides in patients suffering from HIV/AIDS.

PubMed

Gupta, Satish Kumar; Nutan

2013-10-22

Microbicides, primarily used as topical pre-exposure prophylaxis, have been proposed to prevent sexual transmission of HIV. This review covers the trends and challenges in the development of safe and effective microbicides to prevent sexual transmission of HIV Initial phases of microbicide development used such surfactants as nonoxynol-9 (N-9), C13G, and sodium lauryl sulfate, aiming to inactivate the virus. Clinical trials of microbicides based on N-9 and C31G failed to inhibit sexual transmission of HIV. On the contrary, N-9 enhanced susceptibility to sexual transmission of HIV-1. Subsequently, microbicides based on polyanions and a variety of other compounds that inhibit the binding, fusion, or entry of virus to the host cells were evaluated for their efficacy in different clinical setups. Most of these trials failed to show either safety or efficacy for prevention of HIV transmission. The next phase of microbicide development involved antiretroviral drugs. Microbicide in the form of 1% tenofovir vaginal gel when tested in a Phase IIb trial (CAPRISA 004) in a coitally dependent manner revealed that tenofovir gel users were 39% less likely to become HIV-infected compared to placebo control. However, in another trial (VOICE MTN 003), tenofovir gel used once daily in a coitally independent mode failed to show any efficacy to prevent HIV infection. Tenofovir gel is currently in a Phase III safety and efficacy trial in South Africa (FACTS 001) employing a coitally dependent dosing regimen. Further, long-acting microbicide-delivery systems (vaginal ring) for slow release of such antiretroviral drugs as dapivirine are also undergoing clinical trials. Discovering new markers as correlates of protective efficacy, novel long-acting delivery systems with improved adherence in the use of microbicides, discovering new compounds effective against a broad spectrum of HIV strains, developing multipurpose technologies incorporating additional features of efficacy against other sexually transmitted infections, and contraception will help in moving the field of microbicide development forward.

Clinical use of vaginal or rectally applied microbicides in patients suffering from HIV/AIDS

PubMed Central

Gupta, Satish Kumar; Nutan

2013-01-01

Microbicides, primarily used as topical pre-exposure prophylaxis, have been proposed to prevent sexual transmission of HIV. This review covers the trends and challenges in the development of safe and effective microbicides to prevent sexual transmission of HIV Initial phases of microbicide development used such surfactants as nonoxynol-9 (N-9), C13G, and sodium lauryl sulfate, aiming to inactivate the virus. Clinical trials of microbicides based on N-9 and C31G failed to inhibit sexual transmission of HIV. On the contrary, N-9 enhanced susceptibility to sexual transmission of HIV-1. Subsequently, microbicides based on polyanions and a variety of other compounds that inhibit the binding, fusion, or entry of virus to the host cells were evaluated for their efficacy in different clinical setups. Most of these trials failed to show either safety or efficacy for prevention of HIV transmission. The next phase of microbicide development involved antiretroviral drugs. Microbicide in the form of 1% tenofovir vaginal gel when tested in a Phase IIb trial (CAPRISA 004) in a coitally dependent manner revealed that tenofovir gel users were 39% less likely to become HIV-infected compared to placebo control. However, in another trial (VOICE MTN 003), tenofovir gel used once daily in a coitally independent mode failed to show any efficacy to prevent HIV infection. Tenofovir gel is currently in a Phase III safety and efficacy trial in South Africa (FACTS 001) employing a coitally dependent dosing regimen. Further, long-acting microbicide-delivery systems (vaginal ring) for slow release of such antiretroviral drugs as dapivirine are also undergoing clinical trials. Discovering new markers as correlates of protective efficacy, novel long-acting delivery systems with improved adherence in the use of microbicides, discovering new compounds effective against a broad spectrum of HIV strains, developing multipurpose technologies incorporating additional features of efficacy against other sexually transmitted infections, and contraception will help in moving the field of microbicide development forward. PMID:24174883

Cinnamon Bark, Water Soluble Cinnamon Extract, and Metformin as Initial Treatment for Type 2 Diabetes Mellitus: A Randomized, Controlled Trial

DTIC Science & Technology

2016-12-14

REPORT DOCUMENTATION PAGE Form ApprovedOMB No. 0704-0188 1 . REPORT DATE (DD-MM-YYYY) 2. REPORT TYPE 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER 6...estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the...Cinnamon Extract, and Metformin as Initial Treatment for Type 2 Diabetes Mellitus: A Randomized, Controlled Trial. Paul Crawford, MD Clinical Investigation

Simplifying "target" intraocular pressure for different stages of primary open-angle glaucoma and primary angle-closure glaucoma.

PubMed

Sihota, Ramanjit; Angmo, Dewang; Ramaswamy, Deepa; Dada, Tanuj

2018-04-01

Lowering of intraocular pressure is currently the only therapeutic measure for Glaucoma management. Many longterm, randomized trials have shown the efficacy of lowering IOP, either by a percentage of baseline, or to a specified level. This has lead to the concept of 'Target" IOP, a range of IOP on therapy, that would stabilize the Glaucoma/prevent further visual field loss, without significantly affecting a patient's quality of life. A clinical staging of Glaucoma by optic nerve head evaluation and perimetric parameters, allows a patient's eye to be categorized as having - mild, moderate or severe Glaucomatous damage. An initial attempt should be made to achieve the following IOP range for both POAG or PACG after an iridotomy. In mild glaucoma the initial target IOP range could be kept as 15-17 mmHg, for moderate glaucoma 12-15 mmHg and in the severe stage of glaucomatous damage 10-12 mmHg. Factoring in baseline IOP, age, vascular perfusion parameters, and change on perimetry or imaging during follow up, this range may be reassessed over 6 months to a year. "Target" IOP requires further lowering when the patient continues to progress or develops a systemic disease such as a TIA. Conversely, in the event of a very elderly or sick patient with stable nerve and visual field over time, the target IOP could be raised and medications reduced. An appropriate use of medications/laser/surgery to achieve such a "Target" IOP range in POAG or PACG can maintain visual fields and quality of life, preventing Glaucoma blindness.

Maternal high-fat diet during pregnancy and lactation reduces the appetitive behavioral component in female offspring tested in a brief-access taste procedure.

PubMed

Treesukosol, Yada; Sun, Bo; Moghadam, Alexander A; Liang, Nu-Chu; Tamashiro, Kellie L; Moran, Timothy H

2014-04-01

Maternal high-fat diet appears to disrupt several energy balance mechanisms in offspring. Here, female offspring from dams fed a high-fat diet (HF) did not significantly differ in body weight compared with those fed chow (CHOW), when weaned onto chow diet. Yet when presented with both a chow and a high-fat diet, high-fat intake was significantly higher in HF compared with CHOW offspring. To assess taste-based responsiveness, offspring (12 wk old) were tested in 30-min sessions (10-s trials) to a sucrose concentration series in a brief-access taste test. Compared with CHOW, the HF offspring initiated significantly fewer trials but did not significantly differ in the amount of concentration-dependent licking. Thus, rather than affect lick response (consummatory), maternal diet affects spout approach (appetitive), which may be attributed to motivation-related mechanisms. Consistent with this possibility, naltrexone, an opioid receptor antagonist, further reduced trial initiation, but not licking in both groups. With naltrexone administration, the group difference in trial initiation was no longer evident, suggesting differences in endogenous opioid activity between the two groups. Relative expression of μ-opioid receptor in the ventral tegmental area was significantly lower in HF rats. When trial initiation was not required in one-bottle intake tests, no main effect of maternal diet on the intake of sucrose and corn oil emulsions was observed. Thus, the maternal high-fat diet-induced difference in diet preference is not likely due to changes in the sensory orosensory component of the taste stimulus but may depend on alterations in satiety signals or absorptive mechanisms.

Maternal high-fat diet during pregnancy and lactation reduces the appetitive behavioral component in female offspring tested in a brief-access taste procedure

PubMed Central

Sun, Bo; Moghadam, Alexander A.; Liang, Nu-Chu; Tamashiro, Kellie L.; Moran, Timothy H.

2014-01-01

Maternal high-fat diet appears to disrupt several energy balance mechanisms in offspring. Here, female offspring from dams fed a high-fat diet (HF) did not significantly differ in body weight compared with those fed chow (CHOW), when weaned onto chow diet. Yet when presented with both a chow and a high-fat diet, high-fat intake was significantly higher in HF compared with CHOW offspring. To assess taste-based responsiveness, offspring (12 wk old) were tested in 30-min sessions (10-s trials) to a sucrose concentration series in a brief-access taste test. Compared with CHOW, the HF offspring initiated significantly fewer trials but did not significantly differ in the amount of concentration-dependent licking. Thus, rather than affect lick response (consummatory), maternal diet affects spout approach (appetitive), which may be attributed to motivation-related mechanisms. Consistent with this possibility, naltrexone, an opioid receptor antagonist, further reduced trial initiation, but not licking in both groups. With naltrexone administration, the group difference in trial initiation was no longer evident, suggesting differences in endogenous opioid activity between the two groups. Relative expression of μ-opioid receptor in the ventral tegmental area was significantly lower in HF rats. When trial initiation was not required in one-bottle intake tests, no main effect of maternal diet on the intake of sucrose and corn oil emulsions was observed. Thus, the maternal high-fat diet-induced difference in diet preference is not likely due to changes in the sensory orosensory component of the taste stimulus but may depend on alterations in satiety signals or absorptive mechanisms. PMID:24500433

Lorcaserin plus lifestyle modification for weight loss maintenance: Rationale and design for a randomized controlled trial.

PubMed

Tronieri, Jena Shaw; Alfaris, Nasreen; Chao, Ariana M; Pearl, Rebecca L; Alamuddin, Naji; Bakizada, Zayna M; Berkowitz, Robert I; Wadden, Thomas A

2017-08-01

Few studies have examined the efficacy of recently approved medications for chronic weight management in facilitating the maintenance of lost weight. This paper provides an overview of the design and rationale for a trial investigating whether lorcaserin, when combined with behavioral weight loss maintenance sessions (WLM), will facilitate the maintenance of losses of ≥5% of initial weight. In this two-phase trial, participants with obesity will enroll in a 14-week run-in diet program consisting of weekly group lifestyle modification sessions and a 1000-1200kcal/d meal replacement diet. Participants who complete this weight induction phase and lose at least 5% of initial weight will then be randomized to 52weeks of WLM plus lorcaserin or WLM plus placebo. We hypothesize that at 52weeks post randomization, participants assigned to WLM plus lorcaserin will achieve significantly better maintenance of the prior 5% weight loss. We will recruit 182 adults with obesity to participate in the diet run-in, 136 of whom (75%) are expected to become eligible for the randomized controlled trial. Co-primary outcomes include the percentage of participants who maintain a loss of at least 5% of initial weight at week 52 and change in weight (kg) from randomization to week 52. This two-phase design will allow us to determine the potential efficacy of chronic weight management using lorcaserin for maintaining initial losses of at least 5% body weight, induced by the use of a structured meal-replacement diet. This combined approach holds promise of achieving larger long-term weight losses. NCT02388568 on ClinicalTrials.gov. Copyright © 2017 Elsevier Inc. All rights reserved.

The Sustained Influence of an Error on Future Decision-Making.

PubMed

Schiffler, Björn C; Bengtsson, Sara L; Lundqvist, Daniel

2017-01-01

Post-error slowing (PES) is consistently observed in decision-making tasks after negative feedback. Yet, findings are inconclusive as to whether PES supports performance accuracy. We addressed the role of PES by employing drift diffusion modeling which enabled us to investigate latent processes of reaction times and accuracy on a large-scale dataset (>5,800 participants) of a visual search experiment with emotional face stimuli. In our experiment, post-error trials were characterized by both adaptive and non-adaptive decision processes. An adaptive increase in participants' response threshold was sustained over several trials post-error. Contrarily, an initial decrease in evidence accumulation rate, followed by an increase on the subsequent trials, indicates a momentary distraction of task-relevant attention and resulted in an initial accuracy drop. Higher values of decision threshold and evidence accumulation on the post-error trial were associated with higher accuracy on subsequent trials which further gives credence to these parameters' role in post-error adaptation. Finally, the evidence accumulation rate post-error decreased when the error trial presented angry faces, a finding suggesting that the post-error decision can be influenced by the error context. In conclusion, we demonstrate that error-related response adaptations are multi-component processes that change dynamically over several trials post-error.

Phase 0 trials: an industry perspective.

PubMed

Eliopoulos, Helen; Giranda, Vincent; Carr, Robert; Tiehen, Rita; Leahy, Terri; Gordon, Gary

2008-06-15

Worldwide, cancer is a leading cause of morbidity and mortality. An increased understanding of the disease and its process has resulted in a multitude of new targeted therapies. The costs as well as time from drug discovery to market, however, remain staggeringly high and protracted, with the majority of compounds never reaching phase III. The concept of an exploratory or phase 0 trial was introduced as a mechanism to enhance and accelerate the overall process of new oncologic drug development. Performance of a phase 0 study allows researchers to better understand the pharmacokinetic and pharmacodynamic properties of compounds in human subjects before initiation of phase I trials. Data gleaned from a phase 0 trial are beneficial not only in prioritizing promising compounds but also in allowing the modification of phase I study design before initiation. To date, few researchers have taken advantage of the potential benefits of phase 0 trials. This review focuses on the purpose as well as the potential merits of phase 0 trials from the perspective of a pharmaceutical company. The review summarizes the experience of a team of researchers with ABT-888, a novel poly (ADP-ribose) polymerase agent that inhibits an enzyme critical for repairing damage to DNA, which is one of the first compounds to be investigated using the phase 0 clinical trial design.

Immobilization of swift foxes with ketamine hydrochloride-xylazine hydrochloride

USGS Publications Warehouse

Telesco, R.L.; Sovada, Marsha A.

2002-01-01

There is an increasing need to develop field immobilization techniques that allow researchers to handle safely swift foxes (Vulpes velox) with minimal risk of stress or injury. We immobilized captive swift foxes to determine the safety and effectiveness of ketamine hydrochloride and xylazine hydrochloride at different dosages. We attempted to determine appropriate dosages to immobilize swift foxes for an adequate field-handling period based on three anesthesia intervals (induction period, immobilization period, and recovery period) and physiologic responses (rectal temperature, respiration rate, and heart rate). Between October 1998–July 1999, we conducted four trials, evaluating three different dosage ratios of ketamine and xylazine (2.27:1.2, 5.68:1.2, and 11.4:1.2 mg/kg ketamine:mg/kg xylazine, respectively), followed by a fourth trial with a higher dosage at the median ratio (11.4 mg/kg ketamine:2.4 mg/kg xylazine). We found little difference in induction and recovery periods among trials 1–3, but immobilization time increased with increasing dosage (P<0.08). Both the immobilization period and recovery period increased in trial 4 compared with trials 1–3 (P≤0.03). There was a high variation in responses of individual foxes across trials, making it difficult to identify an appropriate dosage for field handling. Heart rate and respiration rates were depressed but all physiologic measures remained within normal parameters established for domestic canids. We recommend a dosage ratio of 10 mg/kg ketamine to 1 mg/kg xylazine to immobilize swift foxes for field handling.

A baiting system for delivery of an oral plague vaccine to black-tailed prairie dogs

USGS Publications Warehouse

Creekmore, Terry E.; Rocke, Tonie E.; Hurley, J.

2002-01-01

Laboratory and field studies were conducted between July and October 1999 to identify bait preference, biomarker efficacy, and bait acceptance rates for delivering an oral plague vaccine to black-tailed prairie dogs (Cynomys ludovicianus). Twenty juvenile captive prairie dogs were offered alfalfa baits containing either alfalfa, alfalfa and 5% molasses, or alfalfa, 5% molasses and 4% salt. Based on the results of these trials we selected a bait containing alfalfa, 7% molasses, and 1% salt for field trials to determine bait acceptance rates by free-ranging animals. The biomarkers DuPont Blue dye, iophenoxic acid, and tetracycline hydrochloride were orally administered to captive prairie dogs to determine their efficacy. Only tetracycline proved effective as a biomarker. Two field trials were conducted at separate prairie dog colonies located at the Buffalo Gap National Grassland (Pennington County, South Dakota, USA). In Trial 1, three baits containing tetracycline were distributed around each active burrow entrance and an additional bait was placed inside the burrow (1,276 baits total). In Trial 2, baits were distributed at the same density per burrow as Trial 1, but along transects spaced 10 m apart (1,744 baits total). Trapping began 3 days after bait distribution, and 30 prairie dogs then were captured at each site to determine the percentage of animals marked. In Trial 1, 67% of the prairie dogs captured had tetracycline deposits indicative of bait consumption. In Trial 2, 83% of the prairie dogs had ingested a bait. Approximately 15% of the animals in both trials ate more than one bait. Fleas (Opisocrostis hirsutus) were found on 64 of 70 (91%) of the prairie dogs captured during this study.

Ovarian cancer patients’ and their family members’ perspectives on novel vaccine and virotherapy trials

PubMed Central

Breitkopf, Carmen Radecki; Ridgeway, Jennifer L; Asiedu, Gladys B; Carroll, Katherine; Tenney, Meaghan; Jatoi, Aminah

2016-01-01

Background/Aims Some of the most promising avenues of cancer clinical investigation center on immunotherapeutic approaches. These approaches have provided notable gains in cancer therapeutics with recent FDA approvals of agents of this class in several types of cancer, although gains for ovarian cancer lag behind. This study examined perceptions of therapeutic trials including immunotherapy and virotherapy among ovarian cancer patients and their family members. Methods Seventy-two semi-structured qualitative interviews were conducted with 33 patients and 39 family members at two National Cancer Institute-designated comprehensive cancer centers. Eligible patients were diagnosed with epithelial ovarian, primary peritoneal, or fallopian tube carcinoma and had experience with clinical trial conversations; family members were nominated by patients and interviewed separately. Applied thematic analysis was used to understand and interpret the data. Results More participants were aware of vaccine trials than virus trials, although more than half had heard of at least one of them. Initial reactions to vaccine trials were generally favorable. For many, childhood experience with vaccines lent a familiar frame of reference. Virus trials elicited more negative initial reactions, including the use of adjectives such as “scary” and “dreadful.” Viruses seemed contagious or difficult to control. Increased receptivity to these trials occurred in the context of limited therapeutic options and cancer recurrence. Most participants, including those not immediately drawn to these types of trials, indicated openness to learning more. Conclusions Although vaccine and viral trials are both immunologically-based therapeutic approaches, patients who are offered these trials may perceive their potential benefit and safety quite differently. There is a need to consider terminology, solicit and address “gut reactions,” and provide information that enables patients and their family members to better understand the science behind these trials. PMID:27353282

DSM-5 field trials in the United States and Canada, Part I: study design, sampling strategy, implementation, and analytic approaches.

PubMed

Clarke, Diana E; Narrow, William E; Regier, Darrel A; Kuramoto, S Janet; Kupfer, David J; Kuhl, Emily A; Greiner, Lisa; Kraemer, Helena C

2013-01-01

This article discusses the design,sampling strategy, implementation,and data analytic processes of the DSM-5 Field Trials. The DSM-5 Field Trials were conducted by using a test-retest reliability design with a stratified sampling approach across six adult and four pediatric sites in the United States and one adult site in Canada. A stratified random sampling approach was used to enhance precision in the estimation of the reliability coefficients. A web-based research electronic data capture system was used for simultaneous data collection from patients and clinicians across sites and for centralized data management.Weighted descriptive analyses, intraclass kappa and intraclass correlation coefficients for stratified samples, and receiver operating curves were computed. The DSM-5 Field Trials capitalized on advances since DSM-III and DSM-IV in statistical measures of reliability (i.e., intraclass kappa for stratified samples) and other recently developed measures to determine confidence intervals around kappa estimates. Diagnostic interviews using DSM-5 criteria were conducted by 279 clinicians of varied disciplines who received training comparable to what would be available to any clinician after publication of DSM-5.Overall, 2,246 patients with various diagnoses and levels of comorbidity were enrolled,of which over 86% were seen for two diagnostic interviews. A range of reliability coefficients were observed for the categorical diagnoses and dimensional measures. Multisite field trials and training comparable to what would be available to any clinician after publication of DSM-5 provided “real-world” testing of DSM-5 proposed diagnoses.

Postmenopausal hormone therapy and regional brain volumes: the WHIMS-MRI Study.

PubMed

Resnick, S M; Espeland, M A; Jaramillo, S A; Hirsch, C; Stefanick, M L; Murray, A M; Ockene, J; Davatzikos, C

2009-01-13

To determine whether menopausal hormone therapy (HT) affects regional brain volumes, including hippocampal and frontal regions. Brain MRI scans were obtained in a subset of 1,403 women aged 71-89 years who participated in the Women's Health Initiative Memory Study (WHIMS). WHIMS was an ancillary study to the Women's Health Initiative, which consisted of two randomized, placebo-controlled trials: 0.625 mg conjugated equine estrogens (CEE) with or without 2.5 mg medroxyprogesterone acetate (MPA) in one daily tablet. Scans were performed, on average, 3.0 years post-trial for the CEE + MPA trial and 1.4 years post-trial for the CEE-Alone trial; average on-trial follow-up intervals were 4.0 years for CEE + MPA and 5.6 years for CEE-Alone. Total brain, ventricular, hippocampal, and frontal lobe volumes, adjusted for age, clinic site, estimated intracranial volume, and dementia risk factors, were the main outcome variables. Compared with placebo, covariate-adjusted mean frontal lobe volume was 2.37 cm(3) lower among women assigned to HT (p = 0.004), mean hippocampal volume was slightly (0.10 cm(3)) lower (p = 0.05), and differences in total brain volume approached significance (p = 0.07). Results were similar for CEE + MPA and CEE-Alone. HT-associated reductions in hippocampal volumes were greatest in women with the lowest baseline Modified Mini-Mental State Examination scores (scores <90). Conjugated equine estrogens with or without MPA are associated with greater brain atrophy among women aged 65 years and older; however, the adverse effects are most evident in women experiencing cognitive deficits before initiating hormone therapy.

The POST trial: initial post-market experience of the Penumbra system: revascularization of large vessel occlusion in acute ischemic stroke in the United States and Europe.

PubMed

Tarr, Robert; Hsu, Dan; Kulcsar, Zsolt; Bonvin, Christophe; Rufenacht, Daniel; Alfke, Karsten; Stingele, Robert; Jansen, Olav; Frei, Donald; Bellon, Richard; Madison, Michael; Struffert, Tobias; Dorfler, Arnd; Grunwald, Iris Q; Reith, Wolfgang; Haass, Anton

2010-12-01

The purpose of this study was to assess the initial post-market experience of the device and how it is compared with the Penumbra Pivotal trial used to support the 510k application. A retrospective case review of 157 consecutive patients treated with the Penumbra system at seven international centers was performed. Primary endpoints were revascularization of the target vessel (TIMI score of 2 or 3), good functional outcome as defined by a modified Rankin scale (mRS) score of ≤2 and incidence of procedural serious adverse events. Results were compared with those of the Penumbra pivotal trial. A total of 157 vessels were treated. Mean baseline values at enrollment were: age 65 years, NIHSS score 16. After use of the Penumbra system, 87% of the treated vessels were revascularized to TIMI 2 (54%) or 3 (33%) as compared with 82% reported in the Pivotal trial. Nine procedural serious adverse events were reported in 157 patients (5.7%). All-cause mortality was 20% (32/157), and 41% had a mRS of ≤2 at 90-day follow-up as compared with only 25% in the Pivotal trial. Patients who were successfully revascularized by the Penumbra system had significantly better outcomes than those who were not. Initial post-market experience of the Penumbra system revealed that the revascularization rate and safety profile of the device are comparable to those reported in the Pivotal trial. However, the proportion of patients who had good functional outcome was higher than expected.

Behavioral and locomotor measurements using an open field activity monitoring system for skeletal muscle diseases.

PubMed

Tatem, Kathleen S; Quinn, James L; Phadke, Aditi; Yu, Qing; Gordish-Dressman, Heather; Nagaraju, Kanneboyina

2014-09-29

The open field activity monitoring system comprehensively assesses locomotor and behavioral activity levels of mice. It is a useful tool for assessing locomotive impairment in animal models of neuromuscular disease and efficacy of therapeutic drugs that may improve locomotion and/or muscle function. The open field activity measurement provides a different measure than muscle strength, which is commonly assessed by grip strength measurements. It can also show how drugs may affect other body systems as well when used with additional outcome measures. In addition, measures such as total distance traveled mirror the 6 min walk test, a clinical trial outcome measure. However, open field activity monitoring is also associated with significant challenges: Open field activity measurements vary according to animal strain, age, sex, and circadian rhythm. In addition, room temperature, humidity, lighting, noise, and even odor can affect assessment outcomes. Overall, this manuscript provides a well-tested and standardized open field activity SOP for preclinical trials in animal models of neuromuscular diseases. We provide a discussion of important considerations, typical results, data analysis, and detail the strengths and weaknesses of open field testing. In addition, we provide recommendations for optimal study design when using open field activity in a preclinical trial.

Design and Development of a New Multi-Projection X-Ray System for Chest Imaging

NASA Astrophysics Data System (ADS)

Chawla, Amarpreet S.; Boyce, Sarah; Washington, Lacey; McAdams, H. Page; Samei, Ehsan

2009-02-01

Overlapping anatomical structures may confound the detection of abnormal pathology, including lung nodules, in conventional single-projection chest radiography. To minimize this fundamental limiting factor, a dedicated digital multi-projection system for chest imaging was recently developed at the Radiology Department of Duke University. We are reporting the design of the multi-projection imaging system and its initial performance in an ongoing clinical trial. The system is capable of acquiring multiple full-field projections of the same patient along both the horizontal and vertical axes at variable speeds and acquisition frame rates. These images acquired in rapid succession from slightly different angles about the posterior-anterior (PA) orientation can be correlated to minimize the influence of overlying anatomy. The developed system has been tested for repeatability and motion blur artifacts to investigate its robustness for clinical trials. Excellent geometrical consistency was found in the tube motion, with positional errors for clinical settings within 1%. The effect of tube-motion on the image quality measured in terms of impact on the modulation transfer function (MTF) was found to be minimal. The system was deemed clinic-ready and a clinical trial was subsequently launched. The flexibility of image acquisition built into the system provides a unique opportunity to easily modify it for different clinical applications, including tomosynthesis, correlation imaging (CI), and stereoscopic imaging.

Assimilation of concentration measurements for retrieving multiple point releases in atmosphere: A least-squares approach to inverse modelling

NASA Astrophysics Data System (ADS)

Singh, Sarvesh Kumar; Rani, Raj

2015-10-01

The study addresses the identification of multiple point sources, emitting the same tracer, from their limited set of merged concentration measurements. The identification, here, refers to the estimation of locations and strengths of a known number of simultaneous point releases. The source-receptor relationship is described in the framework of adjoint modelling by using an analytical Gaussian dispersion model. A least-squares minimization framework, free from an initialization of the release parameters (locations and strengths), is presented to estimate the release parameters. This utilizes the distributed source information observable from the given monitoring design and number of measurements. The technique leads to an exact retrieval of the true release parameters when measurements are noise free and exactly described by the dispersion model. The inversion algorithm is evaluated using the real data from multiple (two, three and four) releases conducted during Fusion Field Trials in September 2007 at Dugway Proving Ground, Utah. The release locations are retrieved, on average, within 25-45 m of the true sources with the distance from retrieved to true source ranging from 0 to 130 m. The release strengths are also estimated within a factor of three to the true release rates. The average deviations in retrieval of source locations are observed relatively large in two release trials in comparison to three and four release trials.

The burden of proof: The current state of atrial fibrillation prevention and treatment trials.

PubMed

Zakeri, Rosita; Van Wagoner, David R; Calkins, Hugh; Wong, Tom; Ross, Heather M; Heist, E Kevin; Meyer, Timothy E; Kowey, Peter R; Mentz, Robert J; Cleland, John G; Pitt, Bertram; Zannad, Faiez; Linde, Cecilia

2017-05-01

Atrial fibrillation (AF) is an age-related arrhythmia of enormous socioeconomic significance. In recent years, our understanding of the basic mechanisms that initiate and perpetuate AF has evolved rapidly, catheter ablation of AF has progressed from concept to reality, and recent studies suggest lifestyle modification may help prevent AF recurrence. Emerging developments in genetics, imaging, and informatics also present new opportunities for personalized care. However, considerable challenges remain. These include a paucity of studies examining AF prevention, modest efficacy of existing antiarrhythmic therapies, diverse ablation technologies and practice, and limited evidence to guide management of high-risk patients with multiple comorbidities. Studies examining the long-term effects of AF catheter ablation on morbidity and mortality outcomes are not yet completed. In many ways, further progress in the field is heavily contingent on the feasibility, capacity, and efficiency of clinical trials to incorporate the rapidly evolving knowledge base and to provide substantive evidence for novel AF therapeutic strategies. This review outlines the current state of AF prevention and treatment trials, including the foreseeable challenges, as discussed by a unique forum of clinical trialists, scientists, and regulatory representatives in a session endorsed by the Heart Rhythm Society at the 12th Global CardioVascular Clinical Trialists Forum in Washington, DC, December 3-5, 2015. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

An initial trial of a prototype telepathology system featuring static imaging with discrete control of the remote microscope.

PubMed

Winokur, T S; McClellan, S; Siegal, G P; Reddy, V; Listinsky, C M; Conner, D; Goldman, J; Grimes, G; Vaughn, G; McDonald, J M

1998-07-01

Routine diagnosis of pathology images transmitted over telecommunications lines remains an elusive goal. Part of the resistance stems from the difficulty of enabling image selection by the remote pathologist. To address this problem, a telepathology microscope system (TelePath, TeleMedicine Solutions, Birmingham, Ala) that has features associated with static and dynamic imaging systems was constructed. Features of the system include near real time image transmission, provision of a tiled overview image, free choice of any fields at any desired optical magnification, and automated tracking of the pathologist's image selection. All commands and images are discrete, avoiding many inherent problems of full motion video and continuous remote control. A set of 64 slides was reviewed by 3 pathologists in a simulated frozen section environment. Each pathologist provided diagnoses for all 64 slides, as well as qualitative information about the system. Thirty-one of 192 diagnoses disagreed with the reference diagnosis that had been reached before the trial began. Qf the 31, 13 were deferrals and 12 were diagnoses of cases that had a deferral as the reference diagnosis. In 6 cases, the diagnosis disagreed with the reference diagnosis yielding an overall accuracy of 96.9%. Confidence levels in the diagnoses were high. This trial suggests that this system provides high-quality anatomic pathology services, including intraoperative diagnoses, over telecommunications lines.

Advances in Wilms Tumor Treatment and Biology: Progress Through International Collaboration.

PubMed

Dome, Jeffrey S; Graf, Norbert; Geller, James I; Fernandez, Conrad V; Mullen, Elizabeth A; Spreafico, Filippo; Van den Heuvel-Eibrink, Marry; Pritchard-Jones, Kathy

2015-09-20

Clinical trials in Wilms tumor (WT) have resulted in overall survival rates of greater than 90%. This achievement is especially remarkable because improvements in disease-specific survival have occurred concurrently with a reduction of therapy for large patient subgroups. However, the outcomes for certain patient subgroups, including those with unfavorable histologic and molecular features, bilateral disease, and recurrent disease, remain well below the benchmark survival rate of 90%. Therapy for WT has been advanced in part by an increasingly complex risk-stratification system based on patient age; tumor stage, histology, and volume; response to chemotherapy; and loss of heterozygosity at chromosomes 1p and 16q. A consequence of this system has been the apportionment of patients into such small subgroups that only collaboration between large international WT study groups will support clinical trials that are sufficiently powered to answer challenging questions that move the field forward. This article gives an overview of the Children's Oncology Group and International Society of Pediatric Oncology approaches to WT and focuses on four subgroups (stage IV, initially inoperable, bilateral, and relapsed WT) for which international collaboration is pressing. In addition, biologic insights resulting from collaborative laboratory research are discussed. A coordinated expansion of international collaboration in both clinical trials and laboratory science will provide real opportunity to improve the treatment and outcomes for children with renal tumors on a global level. © 2015 by American Society of Clinical Oncology.

Stem cells in clinical trials for treatment of retinal degeneration.

PubMed

Klassen, Henry

2016-01-01

After decades of basic science research involving the testing of regenerative strategies in animal models of retinal degenerative diseases, a number of clinical trials are now underway, with additional trials set to begin shortly. These efforts will evaluate the safety and preliminary efficacy of cell-based products in the eyes of patients with a number of retinal conditions, notably including age-related macular degeneration, retinitis pigmentosa and Stargardt's disease. This review considers the scientific work and early trials with fetal cells and tissues that set the stage for the current clinical investigatory work, as well the trials themselves, specifically those either now completed, underway or close to initiation. The cells of interest include retinal pigment epithelial cells derived from embryonic stem or induced pluripotent stem cells, undifferentiated neural or retinal progenitors or cells from the vascular/bone marrow compartment or umbilical cord tissue. Degenerative diseases of the retina represent a popular target for emerging cell-based therapeutics and initial data from early stage clinical trials suggest that short-term safety objectives can be met in at least some cases. The question of efficacy will require additional time and testing to be adequately resolved.

The Value of Pre-Screening in the Alzheimer's Prevention Initiative (API) Autosomal Dominant Alzheimer's Disease Trial.

PubMed

Rios-Romenets, S; Giraldo-Chica, M; López, H; Piedrahita, F; Ramos, C; Acosta-Baena, N; Muñoz, C; Ospina, P; Tobón, C; Cho, W; Ward, M; Langbaum, J B; Tariot, P N; Reiman, E M; Lopera, F

2018-01-01

The Alzheimer's Prevention Initiative (API) Autosomal Dominant Alzheimer's Disease (ADAD) trial evaluates the anti-amyloid-β antibody crenezumab in cognitively unimpaired persons who, based on genetic background and age, are at high imminent risk of clinical progression, and provides a powerful test of the amyloid hypothesis. The Neurosciences Group of Antioquia implemented a pre-screening process with the goals of decreasing screen failures and identifying participants most likely to adhere to trial requirements of the API ADAD trial in cognitively unimpaired members of Presenilin1 E280A mutation kindreds. The pre-screening failure rate was 48.2%: the primary reason was expected inability to comply with the protocol, chiefly due to work requirements. More carriers compared to non-carriers, and more males compared to females, failed pre-screening. Carriers with illiteracy or learning/comprehension difficulties failed pre-screening more than non-carriers. With the Colombian API Registry and our prescreening efforts, we randomized 169 30-60 year-old cognitively unimpaired carriers and 83 non-carriers who agreed to participate in the trial for at least 60 months. Our findings suggest multiple benefits of implementing a pre-screening process for enrolling prevention trials in ADAD.

Quality of clinical trials: A moving target

PubMed Central

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

Assessment Data-Informed Guidance to Individualize Kindergarten Reading Instruction: Findings from a Cluster-Randomized Control Field Trial

ERIC Educational Resources Information Center

Al Otaiba, Stephanie; Connor, Carol M.; Folsom, Jessica S.; Greulich, Luana; Meadows, Jane; Li, Zhi

2011-01-01

The purpose of this cluster-randomized control field trial was to examine whether kindergarten teachers could learn to differentiate classroom reading instruction using Individualized Student Instruction for Kindergarten (ISI-K) and to test the efficacy of differentiation on reading outcomes. The study involved 14 schools, 23 ISI-K (n = 305…

Formulations of the endophytic bacterium Bacillus subtilis Tu-100 suppress Sclerotinia sclerotiorum on oilseed rape and improve plant vigor in field trials conducted at separate locations

USDA-ARS?s Scientific Manuscript database

Sclerotinia sclerotiorum causes serious yield losses in crops in The People’s Republic of China. Two formulations of oilseed rape seed containing the endophytic bacterium Bacillus subtilis Tu-100 were evaluated for suppression of this pathogen in field trials conducted at two independent locations....

SUPERFUND TREATABILITY CLEARINGHOUSE: FULL ...

EPA Pesticide Factsheets

This treatability study reports on the results of one of a series of field trials using various remedial action technologies that may be capable of restoring Herbicide Orange (HO)XDioxin contaminated sites. A full-scale field trial using a rotary kiln incinerator capable of processing up to 6 tons per hour of dioxin contaminated soil was conducted at the Naval Construction Battalion Center, Gulfport, MS. publish information

Impact of an indigenous microbial enhanced oil recovery field trial on microbial community structure in a high pour-point oil reservoir.

PubMed

Zhang, Fan; She, Yue-Hui; Li, Hua-Min; Zhang, Xiao-Tao; Shu, Fu-Chang; Wang, Zheng-Liang; Yu, Long-Jiang; Hou, Du-Jie

2012-08-01

Based on preliminary investigation of microbial populations in a high pour-point oil reservoir, an indigenous microbial enhanced oil recovery (MEOR) field trial was carried out. The purpose of the study is to reveal the impact of the indigenous MEOR process on microbial community structure in the oil reservoir using 16Sr DNA clone library technique. The detailed monitoring results showed significant response of microbial communities during the field trial and large discrepancies of stimulated microorganisms in the laboratory and in the natural oil reservoir. More specifically, after nutrients injection, the original dominant populations of Petrobacter and Alishewanella in the production wells almost disappeared. The expected desirable population of Pseudomonas aeruginosa, determined by enrichment experiments in laboratory, was stimulated successfully in two wells of the five monitored wells. Unexpectedly, another potential population of Pseudomonas pseudoalcaligenes which were not detected in the enrichment culture in laboratory was stimulated in the other three monitored production wells. In this study, monitoring of microbial community displayed a comprehensive alteration of microbial populations during the field trial to remedy the deficiency of culture-dependent monitoring methods. The results would help to develop and apply more MEOR processes.

Targeted Therapies Improve Survival for Patients with Pancreatic Neuroendocrine Tumors

Cancer.gov

In 2011, based on initial findings from two clinical trials, the Food and Drug Administration approved sunitinib and everolimus for patients with pancreatic neuroendocrine tumors. Updated results from the everolimus trial were published in September 2016.

Survival in prostate cancer prevention trial detailed

Cancer.gov

In the NCI-sponsored Prostate Cancer Prevention Trial, initial findings from a decade ago showed that the drug finasteride significantly reduced the risk of prostate cancer, but among those who did develop prostate cancer, paradoxically, the drug was asso

Integrating the behavioral and neural dynamics of response selection in a dual-task paradigm: a dynamic neural field model of Dux et al. (2009).

PubMed

Buss, Aaron T; Wifall, Tim; Hazeltine, Eliot; Spencer, John P

2014-02-01

People are typically slower when executing two tasks than when only performing a single task. These dual-task costs are initially robust but are reduced with practice. Dux et al. (2009) explored the neural basis of dual-task costs and learning using fMRI. Inferior frontal junction (IFJ) showed a larger hemodynamic response on dual-task trials compared with single-task trial early in learning. As dual-task costs were eliminated, dual-task hemodynamics in IFJ reduced to single-task levels. Dux and colleagues concluded that the reduction of dual-task costs is accomplished through increased efficiency of information processing in IFJ. We present a dynamic field theory of response selection that addresses two questions regarding these results. First, what mechanism leads to the reduction of dual-task costs and associated changes in hemodynamics? We show that a simple Hebbian learning mechanism is able to capture the quantitative details of learning at both the behavioral and neural levels. Second, is efficiency isolated to cognitive control areas such as IFJ, or is it also evident in sensory motor areas? To investigate this, we restrict Hebbian learning to different parts of the neural model. None of the restricted learning models showed the same reductions in dual-task costs as the unrestricted learning model, suggesting that efficiency is distributed across cognitive control and sensory motor processing systems.

Initial pen and field assessment of baits to use in oral rabies vaccination of Formosan ferret-badgers in response to the re-emergence of rabies in Taiwan.

PubMed

Wallace, Ryan M; Lai, Yuching; Doty, Jeffrey B; Chen, Chen-Chih; Vora, Neil M; Blanton, Jesse D; Chang, Susan S; Cleaton, Julie M; Pei, Kurtis J C

2018-01-01

Taiwan had been considered rabies free since 1961, until a newly established wildlife disease surveillance program identified rabies virus transmission within the Formosan ferret-badger (Melogale moschata subaurantiaca) in 2013. Ferret-badgers occur throughout southern China and Southeast Asia, but their ecological niche is not well described. As an initial feasibility assessment for potential rabies control measures, field camera trapping and pen assessment of 6 oral rabies vaccine (ORV) baits were conducted in Taiwan in 2013. 46 camera nights were recorded; 6 Formosan ferret-badgers and 14 non-target mammals were sighted. No baits were consumed by ferret-badgers and 8 were consumed by non-target mammals. Penned ferret-badgers ingested 5 of the 18 offered baits. When pen and field trials were combined, and analyzed for palatability, ferret-badgers consumed 1 of 9 marshmallow baits (11.1%), 1 of 21 fishmeal baits (4.8%), 0 of 3 liver baits, and 3 of 3 fruit-flavored baits. It took an average of 261 minutes before ferret-badgers made oral contact with the non-fruit flavored baits, and 34 minutes for first contact with the fruit-based bait. Overall, ferret-badgers sought out the fruit baits 8 times faster, spent a greater proportion of time eating fruit baits, and were 7.5 times more likely to have ruptured the vaccine container of the fruit-based bait. Ferret-badgers are now recognized as rabies reservoir species in China and Taiwan, through two independent 'dog to ferret-badger' host-shift events. Species of ferret-badgers can be found throughout Indochina, where they may be an unrecognized rabies reservoir. Findings from this initial study underscore the need for further captive and field investigations of fruit-based attractants or baits developed for small meso-carnivores. Non-target mammals' competition for baits, ants, bait design, and dense tropical landscape represent potential challenges to effective ORV programs that will need to be considered in future studies.

Initial pen and field assessment of baits to use in oral rabies vaccination of Formosan ferret-badgers in response to the re-emergence of rabies in Taiwan

PubMed Central

Wallace, Ryan M.; Lai, Yuching; Doty, Jeffrey B.; Chen, Chen-Chih; Vora, Neil M.; Blanton, Jesse D.; Chang, Susan S.; Pei, Kurtis J. C.

2018-01-01

Background Taiwan had been considered rabies free since 1961, until a newly established wildlife disease surveillance program identified rabies virus transmission within the Formosan ferret-badger (Melogale moschata subaurantiaca) in 2013. Ferret-badgers occur throughout southern China and Southeast Asia, but their ecological niche is not well described. Methodology/Principle findings As an initial feasibility assessment for potential rabies control measures, field camera trapping and pen assessment of 6 oral rabies vaccine (ORV) baits were conducted in Taiwan in 2013. 46 camera nights were recorded; 6 Formosan ferret-badgers and 14 non-target mammals were sighted. No baits were consumed by ferret-badgers and 8 were consumed by non-target mammals. Penned ferret-badgers ingested 5 of the 18 offered baits. When pen and field trials were combined, and analyzed for palatability, ferret-badgers consumed 1 of 9 marshmallow baits (11.1%), 1 of 21 fishmeal baits (4.8%), 0 of 3 liver baits, and 3 of 3 fruit-flavored baits. It took an average of 261 minutes before ferret-badgers made oral contact with the non-fruit flavored baits, and 34 minutes for first contact with the fruit-based bait. Overall, ferret-badgers sought out the fruit baits 8 times faster, spent a greater proportion of time eating fruit baits, and were 7.5 times more likely to have ruptured the vaccine container of the fruit-based bait. Conclusions/Significance Ferret-badgers are now recognized as rabies reservoir species in China and Taiwan, through two independent ‘dog to ferret-badger’ host-shift events. Species of ferret-badgers can be found throughout Indochina, where they may be an unrecognized rabies reservoir. Findings from this initial study underscore the need for further captive and field investigations of fruit-based attractants or baits developed for small meso-carnivores. Non-target mammals’ competition for baits, ants, bait design, and dense tropical landscape represent potential challenges to effective ORV programs that will need to be considered in future studies. PMID:29293591

The reliability of a VISION COACH task as a measure of psychomotor skills.

PubMed

Xi, Yubin; Rosopa, Patrick J; Mossey, Mary; Crisler, Matthew C; Drouin, Nathalie; Kopera, Kevin; Brooks, Johnell O

2014-10-01

The VISION COACH™ interactive light board is designed to test and enhance participants' psychomotor skills. The primary goal of this study was to examine the test-retest reliability of the Full Field 120 VISION COACH task. One hundred eleven male and 131 female adult participants completed six trials where they responded to 120 randomly distributed lights displayed on the VISION COACH interactive light board. The mean time required for a participant to complete a trial was 101 seconds. Intraclass correlation coefficients, ranging from 0.962 to 0.987 suggest the VISION COACH Full Field 120 task was a reliable task. Cohen's d's of adjacent pairs of trials suggest learning effects did not negatively affect reliability after the third trial.

COMPUTERIZED EXPERT SYSTEM FOR EVALUATION OF AUTOMATED VISUAL FIELDS FROM THE ISCHEMIC OPTIC NEUROPATHY DECOMPRESSION TRIAL: METHODS, BASELINE FIELDS, AND SIX-MONTH LONGITUDINAL FOLLOW-UP

PubMed Central

Feldon, Steven E

2004-01-01

ABSTRACT Purpose To validate a computerized expert system evaluating visual fields in a prospective clinical trial, the Ischemic Optic Neuropathy Decompression Trial (IONDT). To identify the pattern and within-pattern severity of field defects for study eyes at baseline and 6-month follow-up. Design Humphrey visual field (HVF) change was used as the outcome measure for a prospective, randomized, multi-center trial to test the null hypothesis that optic nerve sheath decompression was ineffective in treating nonarteritic anterior ischemic optic neuropathy and to ascertain the natural history of the disease. Methods An expert panel established criteria for the type and severity of visual field defects. Using these criteria, a rule-based computerized expert system interpreted HVF from baseline and 6-month visits for patients randomized to surgery or careful follow-up and for patients who were not randomized. Results A computerized expert system was devised and validated. The system was then used to analyze HVFs. The pattern of defects found at baseline for patients randomized to surgery did not differ from that of patients randomized to careful follow-up. The most common pattern of defect was a superior and inferior arcuate with central scotoma for randomized eyes (19.2%) and a superior and inferior arcuate for nonrandomized eyes (30.6%). Field patterns at 6 months and baseline were not different. For randomized study eyes, the superior altitudinal defects improved (P = .03), as did the inferior altitudinal defects (P = .01). For nonrandomized study eyes, only the inferior altitudinal defects improved (P = .02). No treatment effect was noted. Conclusions A novel rule-based expert system successfully interpreted visual field defects at baseline of eyes enrolled in the IONDT. PMID:15747764

Differences in Investigator-Initiated Trials between Japan and Other Countries: Analyses of Clinical Trials Sponsored by Academia and Government in the ClinicalTrials.gov Registry and in the Three Japanese Registries.

PubMed

Ito, Tatsuya

2016-01-01

Following the amendment of the Pharmaceutical Affairs Law in Japan in 2003 researchers were permitted to begin investigator-initiated trials (IITs). In subsequent years, however, the number of IITs remained low. In other countries in Asia as well as in Europe, North America, and South Africa, the number of IITs has increased over the past decade. The differences in the characteristics of IITs between Japan and other countries are unknown. Some studies have analyzed the characteristics of all clinical trials according to registry databases, but there has been less research focusing on IITs. The purpose of this study is to analyze the characteristics of IITs in the ClinicalTrials.gov registry and in the three Japanese registries, to identify differences in IITs between Japan and other countries. Using Thomson Reuters Pharma™, trials sponsored by academia and government as IITs in 2010 and registered in ClinicalTrials.gov were identified. IITs from 2004 to 2012 in Japan were identified in the three Japanese registries: the University Hospital Medical Information Network Clinical Trials Registry, the Japan Pharmaceutical Information Center Clinical Trials Information, and the Japan Medical Association Center for Clinical Trials, Clinical Trials Registry. Characterization was made of the trial purposes, phases, participants, masking, arms, design, controls, and other data. New and revised IITs registered in ClinicalTrials.gov during 2010 averaged about 40% of all sponsor-identified trials. IITs were nearly all early-phase studies with small numbers of participants. A total of 56 Japanese IITs were found over a period of 8 years, and these were also almost nearly all early-phase studies with small numbers of participants. There appear to be no great differences between Japan and other countries in terms of characteristics of IITs. These results should prompt a new review of the IIT environment in Japan.

Learning and memory performance in breast cancer survivors 2 to 6 years post-treatment: the role of encoding versus forgetting.

PubMed

Root, James C; Andreotti, Charissa; Tsu, Loretta; Ellmore, Timothy M; Ahles, Tim A

2016-06-01

Our previous retrospective analysis of clinically referred breast cancer survivors' performance on learning and memory measures found a primary weakness in initial encoding of information into working memory with intact retention and recall of this same information at a delay. This suggests that survivors may misinterpret cognitive lapses as being due to forgetting when, in actuality, they were not able to properly encode this information at the time of initial exposure. Our objective in this study was to replicate and extend this pattern of performance to a research sample to increase the generalizability of this finding in a sample in which subjects were not clinically referred for cognitive issues. We contrasted learning and memory performance between breast cancer survivors on endocrine therapy 2 to 6 years post-treatment with age- and education-matched healthy controls. We then stratified lower- and higher-performing breast cancer survivors to examine specific patterns of learning and memory performance. Contrasts were generated for four aggregate visual and verbal memory variables from the California Verbal Learning Test-2 (CVLT-2) and the Brown Location Test (BLT): Single-trial Learning: Trial 1 performance, Multiple-trial Learning: Trial 5 performance, Delayed Recall: Long-delay Recall performance, and Memory Errors: False-positive errors. As predicted, breast cancer survivors' performance as a whole was significantly lower on Single-trial Learning than the healthy control group but exhibited no significant difference in Delayed Recall. In the secondary analysis contrasting lower- and higher-performing survivors on cognitive measures, the same pattern of lower Single-trial Learning performance was exhibited in both groups, with the additional finding of significantly weaker Multiple-trial Learning performance in the lower-performing breast cancer group and intact Delayed Recall performance in both groups. As with our earlier finding of weaker initial encoding with intact recall in a cohort of clinically referred breast cancer survivors, our results indicate this same profile in a research sample of breast cancer survivors. Further, when the breast cancer group was stratified by lower and higher performance, both groups exhibited significantly lower performance on initial encoding, with more pronounced encoding weakness in the lower-performing group. As in our previous research, survivors did not lose successfully encoded information over longer delays, either in the lower- or higher-performing group, again arguing against memory decay in survivors. The finding of weaker initial encoding of information together with intact delayed recall in survivors points to specific treatment interventions in rehabilitation of cognitive dysfunction. The finding of weaker initial encoding of information together with intact delayed recall in survivors points to specific treatment interventions in rehabilitation of cognitive dysfunction and is discussed.

Effects of a single inhalative exposure to formaldehyde on the open field behavior of mice.

PubMed

Malek, Fathi A; Möritz, Klaus-Uwe; Fanghänel, Jochen

2004-02-01

The effects of formaldehyde on the explorative behavior and locomotor activity of mice after a single inhalative exposure were examined in an open field. Adult male mice were exposed to approximately 1.1 ppm, 2.3 ppm, or 5.2 ppm formaldehyde vapour for 2 hours and the open field test was carried out two hours after the end of exposure (trial 1) and repeated 24 hours thereafter (trial 2). The following behavioral parameters were quantitatively examined: numbers of crossed floor squares (inner, peripheral, total), sniffing, grooming, rearing, climbing, and incidence of fecal boli. The results of the first trial revealed that the motion activity was significantly reduced in all exposed groups. In the 1.1 ppm group, the frequency of rearing was reduced and that of floor sniffing increased. The exposure to the two higher formaldehyde concentrations caused a significant decrease in total numbers of floor squares crossed by the subjects, air sniffing, and rearing. The open field test on the next day (trial 2) showed that the frequencies of floor sniffing, grooming, and rearing in all formaldehyde groups were significantly altered. In the 2.5 ppm group, an increased incidence of fecal boli was observed. From the results obtained, we conclude that the exposure of male mice to formaldehyde vapour affects their locomotor and explorative activity in the open field, and that some open field parameters are still altered in the exposed animals even after 24 hours.

The Effect of a Multi-Level Intervention on the Initiation of Antiretroviral Therapy (ART) among HIV-Infected Men Who Inject Drugs and Were Diagnosed Late in Thai Nguyen, Vietnam

PubMed Central

Zelaya, Carla E.; Le Minh, Nguyen; Lau, Bryan; Latkin, Carl A.; Viet Ha, Tran; Minh Quan, Vu; Mo, Thi Tran; Sripaipan, Teerada; Davis, Wendy W.; Celentano, David D.; Frangakis, Constantine; Go, Vivian F.

2016-01-01

Background In Vietnam, an estimated 256,000 people are living with HIV, and 58% of HIV-infections reported are among people who inject drugs (PWID). While antiretroviral therapy (ART) is widely available in Vietnam, marginalized hard-to-reach male PWID, demonstrate significantly reduced and delayed access to ART. Methods We investigated the effect of a randomized four-arm multi-level intervention trial on ART initiation among male PWID. Our analysis was conducted among a subset of trial participants (n = 136), who were newly diagnosed as HIV-infected, treatment naïve, and eligible for ART (baseline late diagnosis). The trial arms included: 1, standard of care (HIV testing and counseling); 2, structural-level intervention (door-to-door communications and community video screenings); 3, individual-level intervention (counseling plus group support); and 4, individual-level plus structural-level intervention. In a time-to-event analysis, we used a non-parametric approach for competing risks to estimate cumulative incidence function (CIF) for ART initiation (event of interest) by arm and the difference in CIF for each trial arm as compared to Arm 1. Follow-up was conducted at 6, 12, 18 and 24 months. Data collection occurred from 2009 to 2013. Findings By 24-months, 61.0% initiated ART, and 30.9% had died prior to ART initiation. In the first 6 months, participants in arm 4 (individual plus community intervention) had a 28% (95% confidence interval (CI): 6–50%) increased probability of initiating ART. Despite increasing coverage of ART in all arms throughout follow-up, participants in arm 4 retained a 31% (95% CI: 5–56%) increased probability of initiating ART. The individual and community components of the intervention were only effective when delivered together. Conclusions Marginalized, hard-to-reach men, who do not routinely engage in HIV services, and therefore come into care late, may benefit significantly from both individual counseling and group support, in combination with community-focused stigma reduction, when being referred and attempting to initiate urgently needed ART. PMID:27579772

The Effect of a Multi-Level Intervention on the Initiation of Antiretroviral Therapy (ART) among HIV-Infected Men Who Inject Drugs and Were Diagnosed Late in Thai Nguyen, Vietnam.

PubMed

Zelaya, Carla E; Le Minh, Nguyen; Lau, Bryan; Latkin, Carl A; Viet Ha, Tran; Minh Quan, Vu; Mo, Thi Tran; Sripaipan, Teerada; Davis, Wendy W; Celentano, David D; Frangakis, Constantine; Go, Vivian F

2016-01-01

In Vietnam, an estimated 256,000 people are living with HIV, and 58% of HIV-infections reported are among people who inject drugs (PWID). While antiretroviral therapy (ART) is widely available in Vietnam, marginalized hard-to-reach male PWID, demonstrate significantly reduced and delayed access to ART. We investigated the effect of a randomized four-arm multi-level intervention trial on ART initiation among male PWID. Our analysis was conducted among a subset of trial participants (n = 136), who were newly diagnosed as HIV-infected, treatment naïve, and eligible for ART (baseline late diagnosis). The trial arms included: 1, standard of care (HIV testing and counseling); 2, structural-level intervention (door-to-door communications and community video screenings); 3, individual-level intervention (counseling plus group support); and 4, individual-level plus structural-level intervention. In a time-to-event analysis, we used a non-parametric approach for competing risks to estimate cumulative incidence function (CIF) for ART initiation (event of interest) by arm and the difference in CIF for each trial arm as compared to Arm 1. Follow-up was conducted at 6, 12, 18 and 24 months. Data collection occurred from 2009 to 2013. By 24-months, 61.0% initiated ART, and 30.9% had died prior to ART initiation. In the first 6 months, participants in arm 4 (individual plus community intervention) had a 28% (95% confidence interval (CI): 6-50%) increased probability of initiating ART. Despite increasing coverage of ART in all arms throughout follow-up, participants in arm 4 retained a 31% (95% CI: 5-56%) increased probability of initiating ART. The individual and community components of the intervention were only effective when delivered together. Marginalized, hard-to-reach men, who do not routinely engage in HIV services, and therefore come into care late, may benefit significantly from both individual counseling and group support, in combination with community-focused stigma reduction, when being referred and attempting to initiate urgently needed ART.

Validation of the DIFFAL, HPAC and HotSpot Dispersion Models Using the Full-Scale Radiological Dispersal Device (FSRDD) Field Trials Witness Plate Deposition Dataset.

PubMed

Purves, Murray; Parkes, David

2016-05-01

Three atmospheric dispersion models--DIFFAL, HPAC, and HotSpot--of differing complexities have been validated against the witness plate deposition dataset taken during the Full-Scale Radiological Dispersal Device (FSRDD) Field Trials. The small-scale nature of these trials in comparison to many other historical radiological dispersion trials provides a unique opportunity to evaluate the near-field performance of the models considered. This paper performs validation of these models using two graphical methods of comparison: deposition contour plots and hotline profile graphs. All of the models tested are assessed to perform well, especially considering that previous model developments and validations have been focused on larger-scale scenarios. Of the models, HPAC generally produced the most accurate results, especially at locations within ∼100 m of GZ. Features present within the observed data, such as hot spots, were not well modeled by any of the codes considered. Additionally, it was found that an increase in the complexity of the meteorological data input to the models did not necessarily lead to an improvement in model accuracy; this is potentially due to the small-scale nature of the trials.

Analysis of force profile during a maximum voluntary isometric contraction task.

PubMed

Househam, Elizabeth; McAuley, John; Charles, Thompson; Lightfoot, Timothy; Swash, Michael

2004-03-01

This study analyses maximum voluntary isometric contraction (MVIC) and its measurement by recording the force profile during maximal-effort, 7-s hand-grip contractions. Six healthy subjects each performed three trials repeated at short intervals to study variation from fatigue. These three trials were performed during three separate sessions at daily intervals to look at random variation. A pattern of force development during a trial was identified. An initiation phase, with or without an initiation peak, was followed by a maintenance phase, sometimes with secondary pulses and an underlying decline in force. Of these three MVIC parameters, maximum force during the maintenance phase showed less random variability compared to intertrial fatigue variability than did maximum force during the initiation phase or absolute maximum force. Analysis of MVIC as a task, rather than a single, maximal value reveals deeper levels of motor control in its generation. Thus, force parameters other than the absolute maximum force may be better suited to quantification of muscle performance in health and disease.

Perturbation-Induced False Starts as a Test of the Jirsa–Kelso Excitator Model

PubMed Central

Fink, Philip W.; Kelso, J. A. Scott; Jirsa, Viktor K.

2009-01-01

One difference between the excitator model and other theoretical models of coordination is the mechanism of discrete movement initiation. In addition to an imperative signal common to all discrete movement initiation, the excitator model proposes that movements are initiated when a threshold element in state space, the so-called separatrix, is crossed as a consequence of stimulation or random fluctuations. The existence of a separatrix predicts that false starts will be caused by mechanical perturbations and that they depend on the perturbation's direction. The authors tested this prediction in a reaction-time task to an auditory stimulus. Participants applied perturbations in the direction of motion (i.e., index finger flexion) or opposed to the motion prior to the stimulus on 1/4 of the trials. The authors found false starts in 34% and 9% of trials following flexion perturbations and extension perturbations, respectively, as compared with only 2% of trials without perturbations, confirming a unique prediction of the excitator model. PMID:19201685

Development of a new compact intraoperative magnetic resonance imaging system: concept and initial experience.

PubMed

Morita, Akio; Sameshima, Tetsuro; Sora, Shigeo; Kimura, Toshikazu; Nishimura, Kengo; Itoh, Hirotaka; Shibahashi, Keita; Shono, Naoyuki; Machida, Toru; Hara, Naoko; Mikami, Nozomi; Harihara, Yasushi; Kawate, Ryoichi; Ochiai, Chikayuki; Wang, Weimin; Oguro, Toshiki

2014-06-01

Magnetic resonance imaging (MRI) during surgery has been shown to improve surgical outcomes, but the current intraoperative MRI systems are too large to install in standard operating suites. Although 1 compact system is available, its imaging quality is not ideal. We developed a new compact intraoperative MRI system and evaluated its use for safety and efficacy. This new system has a magnetic gantry: a permanent magnet of 0.23 T and an interpolar distance of 32 cm. The gantry system weighs 2.8 tons and the 5-G line is within the circle of 2.6 m. We created a new field-of-view head coil and a canopy-style radiofrequency shield for this system. A clinical trial was initiated, and the system has been used in 44 patients. This system is significantly smaller than previous intraoperative MRI systems. High-quality T2 images could discriminate tumor from normal brain tissue and identify anatomic landmarks for accurate surgery. The average imaging time was 45.5 minutes, and no clinical complications or MRI system failures occurred. Floating organisms or particles were minimal (1/200 L maximum). This intraoperative, compact, low-magnetic-field MRI system can be installed in standard operating suites to provide relatively high-quality images without sacrificing safety. We believe that such a system facilitates the introduction of the intraoperative MRI.

Development & standardization of a scale to measure socio-economic status in urban & rural communities in India.

PubMed

Tiwari, S C; Kumar, Aditya; Kumar, Ambrish

2005-10-01

The commonly used available scales for measurement of socio-economic status (SES) with some cross regional applicability are old and have lost their relevance. There is a need for the development of a valid and reliable instrument for measurement of SES in rural and urban communities in India. The present study was undertaken to develop a cross regionally applicable scale for the purpose of enlisting true measures of socio-economic items applicable in multilingual, multicultural, multireligious, setting of the country. For developing the scale, seven indicators (house, materials possession, education, occupation, monthly income, land, social participation and understanding), presumably determining the socioeconomic status were selected. These indicators were named as profiles. Thus, initially the scale had seven profiles and every profile contained five alternatives. This instrument was prepared on a 10-point scale. Weightage system of scoring (varying from 2 to 10) was followed from first to sixth profile while the additive pattern of scoring was followed in seventh profile. The final version of the scale was arrived at through three trial administrations on rural and urban families. The basis of selection of the families for the first two trials was stratified random. The validity and reliability of the scale was established through a defined visual analogue scale (VAS) and test-retest methods. Both the initial version as well as the final version of the scale for the measurement of SES of incumbents had seven profiles. The difference between the two versions was in terms of contents and range of items in different categories of SES. The final version was arrived at through field trials and suggestions of the experts. The reliability of the scale was high with a correlation coefficient of 0.998. The new scale appears to be a valid and reliable instrument for the assessment of socio-economic status of the families/individuals from urban as well as rural areas in India.

Evaluation of the persistence of vaccine-induced protection with human vaccines.

PubMed

Vidor, E

2010-01-01

The persistence of protection induced by vaccines is a key aspect of the implementation of human vaccination policies, particularly for ageing populations. At the time of initial licensure, the duration of protection induced by a vaccine is generally only documented by longitudinal follow up of cohorts of subjects enrolled in the pre-licensure trials over a period of 1-5 years. The follow up of these cohorts provides two types of data: antibody kinetics (or another clinically relevant immunological parameter) over time and the disease incidence. Generally, the latter trials, if implemented during the pre-licensure period, are designed to follow-up cohorts in order to demonstrate vaccine efficacy above the minimal level required for the license. For vaccines already licensed, additional tools exist. The use of immunological surrogate markers of protection is a practical way to monitor the duration of protection. Measuring the persistence of circulating antibodies is widely used in human vaccines. For several vaccines, observed data have allowed the creation of mathematical models to predict the antibody persistence over periods of time longer than those effectively documented. Clinical trials assessing the capacity of the immune system to mount a quick anamnestic response upon re-stimulation a long time after initial priming (measurement of immune memory) is also a tool employed to document the duration of protection. The waning of protection can also be demonstrated by an increase of disease incidence in the subsequent 'time-to-last-vaccine administration' age segments. Seroprevalence studies in a given age group of people that were vaccinated under real-life conditions are another way to document the persistence of protection. Finally, case-control studies in outbreak situations or in situations of persisting endemicity can also be used to document the persistence of the vaccine efficacy. All of these tools are used in the development of new vaccines, and also during their use in the field, in order to develop the best (re)vaccination policies. Copyright 2009 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balian, R., E-mail: roger.balian@cea.fr; Vénéroni, M.

Time-dependent expectation values and correlation functions for many-body quantum systems are evaluated by means of a unified variational principle. It optimizes a generating functional depending on sources associated with the observables of interest. It is built by imposing through Lagrange multipliers constraints that account for the initial state (at equilibrium or off equilibrium) and for the backward Heisenberg evolution of the observables. The trial objects are respectively akin to a density operator and to an operator involving the observables of interest and the sources. We work out here the case where trial spaces constitute Lie groups. This choice reduces themore » original degrees of freedom to those of the underlying Lie algebra, consisting of simple observables; the resulting objects are labeled by the indices of a basis of this algebra. Explicit results are obtained by expanding in powers of the sources. Zeroth and first orders provide thermodynamic quantities and expectation values in the form of mean-field approximations, with dynamical equations having a classical Lie–Poisson structure. At second order, the variational expression for two-time correlation functions separates–as does its exact counterpart–the approximate dynamics of the observables from the approximate correlations in the initial state. Two building blocks are involved: (i) a commutation matrix which stems from the structure constants of the Lie algebra; and (ii) the second-derivative matrix of a free-energy function. The diagonalization of both matrices, required for practical calculations, is worked out, in a way analogous to the standard RPA. The ensuing structure of the variational formulae is the same as for a system of non-interacting bosons (or of harmonic oscillators) plus, at non-zero temperature, classical Gaussian variables. This property is explained by mapping the original Lie algebra onto a simpler Lie algebra. The results, valid for any trial Lie group, fulfill consistency properties and encompass several special cases: linear responses, static and time-dependent fluctuations, zero- and high-temperature limits, static and dynamic stability of small deviations.« less

In Defense of the Randomized Controlled Trial for Health Promotion Research

PubMed Central

Rosen, Laura; Manor, Orly; Engelhard, Dan; Zucker, David

2006-01-01

The overwhelming evidence about the role lifestyle plays in mortality, morbidity, and quality of life has pushed the young field of modern health promotion to center stage. The field is beset with intense debate about appropriate evaluation methodologies. Increasingly, randomized designs are considered inappropriate for health promotion research. We have reviewed criticisms against randomized trials that raise philosophical and practical issues, and we will show how most of these criticisms can be overcome with minor design modifications. By providing rebuttal to arguments against randomized trials, our work contributes to building a sound methodological base for health promotion research. PMID:16735622

Clinical Trial Design in Neuroendocrine Tumors.

PubMed

Halperin, Daniel M; Yao, James C

2016-02-01

Neuroendocrine tumors (NETs) present tremendous opportunities for productive clinical investigation, but substantial challenges as well. Investigators must be aware of common pitfalls in study design, informed by an understanding of the history of trials in the field, to make the best use of available data and our patient volunteers. We believe the salient issues in clinical trial design and interpretation in the NET field are patient homogeneity, standardized response assessment, and rigorous design and execution. Whether designing or interpreting a study in patients with NET, these principles should drive assessment. Copyright © 2016 Elsevier Inc. All rights reserved.

Sustained Aeration of Infant Lungs (SAIL) trial: study protocol for a randomized controlled trial.

PubMed

Foglia, Elizabeth E; Owen, Louise S; Thio, Marta; Ratcliffe, Sarah J; Lista, Gianluca; Te Pas, Arjan; Hummler, Helmut; Nadkarni, Vinay; Ades, Anne; Posencheg, Michael; Keszler, Martin; Davis, Peter; Kirpalani, Haresh

2015-03-15

Extremely preterm infants require assistance recruiting the lung to establish a functional residual capacity after birth. Sustained inflation (SI) combined with positive end expiratory pressure (PEEP) may be a superior method of aerating the lung compared with intermittent positive pressure ventilation (IPPV) with PEEP in extremely preterm infants. The Sustained Aeration of Infant Lungs (SAIL) trial was designed to study this question. This multisite prospective randomized controlled unblinded trial will recruit 600 infants of 23 to 26 weeks gestational age who require respiratory support at birth. Infants in both arms will be treated with PEEP 5 to 7 cm H2O throughout the resuscitation. The study intervention consists of performing an initial SI (20 cm H20 for 15 seconds) followed by a second SI (25 cm H2O for 15 seconds), and then PEEP with or without IPPV, as needed. The control group will be treated with initial IPPV with PEEP. The primary outcome is the combined endpoint of bronchopulmonary dysplasia or death at 36 weeks post-menstrual age. www.clinicaltrials.gov , Trial identifier NCT02139800 , Registered 13 May 2014.

Modeling Learning and Memory Using Verbal Learning Tests: Results From ACTIVE

PubMed Central

Gross, Alden L.

2013-01-01

Objective. To investigate the influence of memory training on initial recall and learning. Method. The Advanced Cognitive Training for Independent and Vital Elderly study of community-dwelling adults older than age 65 (n = 1,401). We decomposed trial-level recall in the Auditory Verbal Learning Test (AVLT) and Hopkins Verbal Learning Test (HVLT) into initial recall and learning across trials using latent growth models. Results. Trial-level increases in words recalled in the AVLT and HVLT at each follow-up visit followed an approximately logarithmic shape. Over the 5-year study period, memory training was associated with slower decline in Trial 1 AVLT recall (Cohen’s d = 0.35, p = .03) and steep pre- and posttraining acceleration in learning (d = 1.56, p < .001). Findings were replicated using the HVLT (decline in initial recall, d = 0.60, p = .01; pre- and posttraining acceleration in learning, d = 3.10, p < .001). Because of the immediate training boost, the memory-trained group had a higher level of recall than the control group through the end of the 5-year study period despite faster decline in learning. Discussion. This study contributes to the understanding of the mechanisms by which training benefits memory and expands current knowledge by reporting long-term changes in initial recall and learning, as measured from growth models and by characterization of the impact of memory training on these components. Results reveal that memory training delays the worsening of memory span and boosts learning. PMID:22929389

Modeling learning and memory using verbal learning tests: results from ACTIVE.

PubMed

Gross, Alden L; Rebok, George W; Brandt, Jason; Tommet, Doug; Marsiske, Michael; Jones, Richard N

2013-03-01

To investigate the influence of memory training on initial recall and learning. The Advanced Cognitive Training for Independent and Vital Elderly study of community-dwelling adults older than age 65 (n = 1,401). We decomposed trial-level recall in the Auditory Verbal Learning Test (AVLT) and Hopkins Verbal Learning Test (HVLT) into initial recall and learning across trials using latent growth models. Trial-level increases in words recalled in the AVLT and HVLT at each follow-up visit followed an approximately logarithmic shape. Over the 5-year study period, memory training was associated with slower decline in Trial 1 AVLT recall (Cohen's d = 0.35, p = .03) and steep pre- and posttraining acceleration in learning (d = 1.56, p < .001). Findings were replicated using the HVLT (decline in initial recall, d = 0.60, p = .01; pre- and posttraining acceleration in learning, d = 3.10, p < .001). Because of the immediate training boost, the memory-trained group had a higher level of recall than the control group through the end of the 5-year study period despite faster decline in learning. This study contributes to the understanding of the mechanisms by which training benefits memory and expands current knowledge by reporting long-term changes in initial recall and learning, as measured from growth models and by characterization of the impact of memory training on these components. Results reveal that memory training delays the worsening of memory span and boosts learning.

Transforming the Activation of Clinical Trials.

PubMed

Watters, Julie T; Pitzen, Jason H; Sanders, Linda J; Bruce, Virginia Nickie M; Cornell, Alissa R; Cseko, Gary C; Grace, Janice S; Kwon, Pamela S; Kukla, Andrea K; Lee, Michael S; Monosmith, Michelle D; Myren, John D; Kottschade, Rebecca S; Shaft, Marc N; Weis, Jennifer Jenny A; Welter, Jane C; Bharucha, Adil E

2018-01-01

The Institute of Medicine and US Food and Drug Administration (FDA) recognize that activating clinical trials in the United States is lengthy and inefficient. Downstream consequences include increased expense, suboptimal accrual, move of clinical trials overseas, and delayed availability of treatments for patients. An in-tandem processing initiative is here highlighted that transformed the activation of clinical trials (TACT), reduced the activation time by 70%, and offers a paradigm for enhanced translational readiness. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Estimating Single-Trial Responses in EEG

NASA Technical Reports Server (NTRS)

Shah, A. S.; Knuth, K. H.; Truccolo, W. A.; Mehta, A. D.; Fu, K. G.; Johnston, T. A.; Ding, M.; Bressler, S. L.; Schroeder, C. E.; Clancy, Daniel (Technical Monitor)

2002-01-01

Accurate characterization of single-trial field potential responses is critical from a number of perspectives. For example, it allows differentiation of an evoked response from ongoing EEG. We previously developed the multiple component Event Related Potential (mcERP) algorithm to improve resolution of the single-trial evoked response. The mcERP model states that multiple components, each specified by a stereotypic waveform varying in latency and amplitude from trial to trial, comprise the evoked response. Application of the mcERP algorithm to simulated data with three independent, synthetic components has shown that the model is capable of separating these components and estimating their variability. Application of the model to single trial, visual evoked potentials recorded simultaneously from all V1 laminae in an awake, fixating macaque yielded local and far-field components. Certain local components estimated by the model were distributed in both granular and supragranular laminae. This suggests a linear coupling between the responses of thalamo-recipient neuronal ensembles and subsequent responses of supragranular neuronal ensembles, as predicted by the feedforward anatomy of V1. Our results indicate that the mcERP algorithm provides a valid estimation of single-trial responses. This will enable analyses that depend on trial-to-trial variations and those that require separation of the evoked response from background EEG rhythms

Streamlining Safety Data Collection in Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia Trials: Recommendations of the Clinical Trials Transformation Initiative Antibacterial Drug Development Project Team.

PubMed

Donnelly, Helen; Alemayehu, Demissie; Botgros, Radu; Comic-Savic, Sabrina; Eisenstein, Barry; Lorenz, Benjamin; Merchant, Kunal; Pelfrene, Eric; Reith, Christina; Santiago, Jonas; Tiernan, Rosemary; Wunderink, Richard; Tenaerts, Pamela; Knirsch, Charles

2016-08-15

Resistant bacteria are one of the leading causes of hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP). HABP/VABP trials are complex and difficult to conduct due to the large number of medical procedures, adverse events, and concomitant medications involved. Differences in the legislative frameworks between different regions of the world may also lead to excessive data collection. The Clinical Trials Transformation Initiative (CTTI) seeks to advance antibacterial drug development (ABDD) by streamlining clinical trials to improve efficiency and feasibility while maintaining ethical rigor, patient safety, information value, and scientific validity. In 2013, CTTI engaged a multidisciplinary group of experts to discuss challenges impeding the conduct of HABP/VABP trials. Separate workstreams identified challenges associated with current data collection processes. Experts defined "data collection" as the act of capturing and reporting certain data on the case report form as opposed to recording of data as part of routine clinical care. The ABDD Project Team developed strategies for streamlining safety data collection in HABP/VABP trials using a Quality by Design approach. Current safety data collection processes in HABP/VABP trials often include extraneous information. More targeted strategies for safety data collection in HABP/VABP trials will rely on optimal protocol design and prespecification of which safety data are essential to satisfy regulatory reporting requirements. A consensus and a cultural change in clinical trial design and conduct, which involve recognition of the need for more efficient data collection, are urgently needed to advance ABDD and to improve HABP/VABP trials in particular. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Effects of corn processing, particle size, and diet form on performance of calves in bedded pens.

PubMed

Bateman, H G; Hill, T M; Aldrich, J M; Schlotterbeck, R L

2009-02-01

In a series of 5 trials, Holstein calves from zero to 12 wk old were housed in pens bedded with straw and fed diets to evaluate physical form of starters containing different processed corn on calf performance. Starters were formulated to have similar ingredient and nutrient compositions. Calves, initially less than 1 wk old, were housed in individual pens through 8 wk and weaned at 6 wk in trial 1 and at 4 wk in trials 2 and 3. In trials 4 and 5, calves initially 8 wk old were housed in group pens (6 calves/pen) from 8 to 12 wk. Trial 1 compared feeding calves a pelleted versus textured starter. Trial 2 compared feeding calves a textured starter versus feeding half meal starter with half textured starter. Trial 3 compared feeding calves textured starters containing whole, steam-flaked, or dry rolled corn. Trial 4 compared feeding calves textured starters containing steam-flaked versus dry rolled corn. Trial 5 compared feeding calves textured starters containing whole or dry rolled corn. Measurements included average daily gain (ADG), starter intake, feed efficiency, hip width change, body condition score change, fecal scores, and medical treatments. Physical form of starter feed did not affect any measurements in trials 1, 3, 4, and 5. In trial 2, calves fed starters manufactured with large amounts of fines had 11% less feed intake and 6% slower ADG than calves fed a textured starter. When starters contained similar ingredient and nutrient contents, manufacturing processes did not affect calf performance unless the diet contained a significant amount of fines, which reduced intake and ADG.

First-in-human Phase 1 CRISPR Gene Editing Cancer Trials: Are We Ready?

PubMed

Baylis, Francoise; McLeod, Marcus

2017-01-01

A prospective first-in-human Phase 1 CRISPR gene editing trial in the United States for patients with melanoma, synovial sarcoma, and multiple myeloma offers hope that gene editing tools may usefully treat human disease. An overarching ethical challenge with first-in-human Phase 1 clinical trials, however, is knowing when it is ethically acceptable to initiate such trials on the basis of safety and efficacy data obtained from pre-clinical studies. If the pre-clinical studies that inform trial design are themselves poorly designed - as a result of which the quality of pre-clinical evidence is deficient - then the ethical requirement of scientific validity for clinical research may not be satisfied. In turn, this could mean that the Phase 1 clinical trial will be unsafe and that trial participants will be exposed to risk for no potential benefit. To assist sponsors, researchers, clinical investigators and reviewers in deciding when it is ethically acceptable to initiate first-in-human Phase 1 CRISPR gene editing clinical trials, structured processes have been developed to assess and minimize translational distance between pre-clinical and clinical research. These processes draw attention to various features of internal validity, construct validity, and external validity. As well, the credibility of supporting evidence is to be critically assessed with particular attention to optimism bias, financial conflicts of interest and publication bias. We critically examine the pre-clinical evidence used to justify the first-inhuman Phase 1 CRISPR gene editing cancer trial in the United States using these tools. We conclude that the proposed trial cannot satisfy the ethical requirement of scientific validity because the supporting pre-clinical evidence used to inform trial design is deficient. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Variability of pesticide residues in eggplant units collected from a field trial and marketplaces in Greece.

PubMed

Prodhan, Mohammad Dalower Hossain; Papadakis, Emmanouil-Nikolaos; Papadopoulou-Mourkidou, Euphemia

2018-04-01

Variability of pesticide residues among food items is very important when assessing the risks and food safety for the consumers. Therefore, the present study was undertaken to estimate the unit-to-unit residue variability factors for eggplant. In total, 120 samples from a trial field and 142 samples from different marketplaces in Thessaloniki, Greece, were collected to estimate the variability of pesticide residues in eggplant units. They were extracted by the QuEChERS method and the residues were determined by LC-MS/MS. For the field samples, the unit-to-unit variability factors (VFs) obtained for cypermethrin and deltamethrin residues were 2.54 and 2.51, respectively. The mean residue levels of both pesticides were higher in the composite samples than in the individual samples. The average VFs for the marketplace samples was 3.89. The eggplant units exposed to pesticides were higher in residues than the non-exposed units. The variability factors obtained in the marketplace samples were higher than those in the samples collected from the field trial. A default VF value of 3 for field trials is appropriate for use when assessing the acute dietary intake but a VF for the marketplace samples should be reconsidered with a larger data. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Size of clinical trials and Introductory prices of prophylactic vaccine series

PubMed Central

Weinberg, Steven H.; Butchart, Amy T.; Davis, Matthew M.

2012-01-01

Costs of completing the recommended immunization schedule have increased over the last decade. Access to prophylactic vaccines may become limited due to financing obstacles within current delivery systems. Vaccine prices reflect research and development expenses incurred by vaccine manufacturers, including costs associated with evaluating candidate vaccines in human subjects. If the number of subjects in clinical trials is increasing over time and associated with vaccine price, this may help explain increases in prices of vaccine series. We examined whether: (A) the initial public- and private-sector prices for recommended prophylactic vaccine series licensed and recommended in the US increased from 2000–2011, (B) the number of human subjects per licensed vaccine increased during the time period, and (C) the number of human subjects was associated with the initial public–and private–sector prices of the vaccine series. In regression analyses of 13 vaccines, approval year was not significantly associated with the number of human subjects, initial public-sector prices, or initial private-sector prices. While the number of phase II subjects was not significantly associated with prices, the numbers of phase III and combined late phase (phases II + III) subjects were significantly associated with initial public- and private-sector series prices (p < 0.05). The association between number of subjects and initial prices demonstrated diminishing marginal increases in price with increasing numbers of subjects. These findings may help guide the number of subjects required by the FDA in clinical trials, in order to reduce expenses for manufacturers and thereby help mitigate increases in initial vaccine series prices. PMID:22854668

Size of clinical trials and Introductory prices of prophylactic vaccine series.

PubMed

Weinberg, Steven H; Butchart, Amy T; Davis, Matthew M

2012-08-01

Costs of completing the recommended immunization schedule have increased over the last decade. Access to prophylactic vaccines may become limited due to financing obstacles within current delivery systems. Vaccine prices reflect research and development expenses incurred by vaccine manufacturers, including costs associated with evaluating candidate vaccines in human subjects. If the number of subjects in clinical trials is increasing over time and associated with vaccine price, this may help explain increases in prices of vaccine series. We examined whether: (A) the initial public- and private-sector prices for recommended prophylactic vaccine series licensed and recommended in the US increased from 2000-2011, (B) the number of human subjects per licensed vaccine increased during the time period, and (C) the number of human subjects was associated with the initial public-and private-sector prices of the vaccine series. In regression analyses of 13 vaccines, approval year was not significantly associated with the number of human subjects, initial public-sector prices, or initial private-sector prices. While the number of phase II subjects was not significantly associated with prices, the numbers of phase III and combined late phase (phases II + III) subjects were significantly associated with initial public- and private-sector series prices (p < 0.05). The association between number of subjects and initial prices demonstrated diminishing marginal increases in price with increasing numbers of subjects. These findings may help guide the number of subjects required by the FDA in clinical trials, in order to reduce expenses for manufacturers and thereby help mitigate increases in initial vaccine series prices.

Modeling early sexual initiation among young adolescents using quantum and continuous behavior change methods: implications for HIV prevention.

PubMed

Chen, Xinguang; Lunn, Sonja; Harris, Carole; Li, Xiaoming; Deveaux, Lynette; Marshall, Sharon; Cottrell, Leslie; Stanton, Bonita

2010-10-01

Behavioral research and prevention intervention science efforts have largely been based on hypotheses of linear or rational behavior change. Additional advances in the field may result from the integration of quantum behavior change and catastrophe models. Longitudinal data from a randomized trial for 1241 pre-adolescents 9-12 years old who self-described as virgin were analyzed. Data for 469 virgins in the control group were included for linear and cusp catastrophe models to describe sexual initiation; data for the rest in the intervention group were added for program effect assessment. Self-reported likelihood to have sex was positively associated with actual initiation of sex (OR = 1.72, 95% CI: 1.43-2.06, R² = 0.13). Receipt of a behavioral prevention intervention based on a cognitive model prevented 15.6% (33.0% vs. 48.6%, OR = 0.52, 95% CI: 0.24-1.11) of the participants from initiating sex among only those who reported 'very likely to have sex.' The beta coefficients for the cubic term of the usp assessing three bifurcating variables (planning to have sex, intrinsic rewards from sex and self-efficacy for abstinence) were 0.0726, 0.1116 and 0.1069 respectively; R² varied from 0.49 to 0.54 (p < 0.001 for all). Although an intervention based on a model of continuous behavior change did produce a modest impact on sexual initiation, quantum change has contributed more than continuous change in describing sexual initiation among young adolescents, suggesting the need for quantum change and chaotic models to advance behavioral prevention of HIV/AIDS.

Parametric models to relate spike train and LFP dynamics with neural information processing.

PubMed

Banerjee, Arpan; Dean, Heather L; Pesaran, Bijan

2012-01-01

Spike trains and local field potentials (LFPs) resulting from extracellular current flows provide a substrate for neural information processing. Understanding the neural code from simultaneous spike-field recordings and subsequent decoding of information processing events will have widespread applications. One way to demonstrate an understanding of the neural code, with particular advantages for the development of applications, is to formulate a parametric statistical model of neural activity and its covariates. Here, we propose a set of parametric spike-field models (unified models) that can be used with existing decoding algorithms to reveal the timing of task or stimulus specific processing. Our proposed unified modeling framework captures the effects of two important features of information processing: time-varying stimulus-driven inputs and ongoing background activity that occurs even in the absence of environmental inputs. We have applied this framework for decoding neural latencies in simulated and experimentally recorded spike-field sessions obtained from the lateral intraparietal area (LIP) of awake, behaving monkeys performing cued look-and-reach movements to spatial targets. Using both simulated and experimental data, we find that estimates of trial-by-trial parameters are not significantly affected by the presence of ongoing background activity. However, including background activity in the unified model improves goodness of fit for predicting individual spiking events. Uncovering the relationship between the model parameters and the timing of movements offers new ways to test hypotheses about the relationship between neural activity and behavior. We obtained significant spike-field onset time correlations from single trials using a previously published data set where significantly strong correlation was only obtained through trial averaging. We also found that unified models extracted a stronger relationship between neural response latency and trial-by-trial behavioral performance than existing models of neural information processing. Our results highlight the utility of the unified modeling framework for characterizing spike-LFP recordings obtained during behavioral performance.

Antenatal peer support workers and initiation of breast feeding: cluster randomised controlled trial.

PubMed

MacArthur, Christine; Jolly, Kate; Ingram, Lucy; Freemantle, Nick; Dennis, Cindy-Lee; Hamburger, Ros; Brown, Julia; Chambers, Jackie; Khan, Khalid

2009-01-30

To assess the effectiveness of an antenatal service using community based breastfeeding peer support workers on initiation of breast feeding. Cluster randomised controlled trial. Community antenatal clinics in one primary care trust in a multiethnic, deprived population. 66 antenatal clinics with 2511 pregnant women: 33 clinics including 1140 women were randomised to receive the peer support worker service and 33 clinics including 1371 women were randomised to receive standard care. An antenatal peer support worker service planned to comprise a minimum of two contacts with women to provide advice, information, and support from approximately 24 weeks' gestation within the antenatal clinic or at home. The trained peer support workers were of similar ethnic and sociodemographic backgrounds to their clinic population. Initiation of breast feeding obtained from computerised maternity records of the hospitals where women from the primary care trust delivered. The sample was multiethnic, with only 9.4% of women being white British, and 70% were in the lowest 10th for deprivation. Most of the contacts with peer support workers took place in the antenatal clinics. Data on initiation of breast feeding were obtained for 2398 of 2511 (95.5%) women (1083/1140 intervention and 1315/1371 controls). The groups did not differ for initiation of breast feeding: 69.0% (747/1083) in the intervention group and 68.1% (896/1315) in the control groups; cluster adjusted odds ratio 1.11 (95% confidence interval 0.87 to 1.43). Ethnicity, parity, and mode of delivery independently predicted initiation of breast feeding, but randomisation to the peer support worker service did not. A universal service for initiation of breast feeding using peer support workers provided within antenatal clinics serving a multiethnic, deprived population was ineffective in increasing initiation rates. Current Controlled Trials ISRCTN16126175.

Atypical anticipatory postural adjustments during gait initiation among individuals with sub-acute stroke.

PubMed

Rajachandrakumar, Roshanth; Fraser, Julia E; Schinkel-Ivy, Alison; Inness, Elizabeth L; Biasin, Lou; Brunton, Karen; McIlroy, William E; Mansfield, Avril

2017-02-01

Anticipatory postural adjustments, executed prior to gait initiation, help preserve lateral stability when stepping. Atypical patterns of anticipatory activity prior to gait initiation may occur in individuals with unilateral impairment (e.g., stroke). This study aimed to determine the prevalence, correlates, and consequences of atypical anticipatory postural adjustment patterns prior to gait initiation in a sub-acute stroke population. Forty independently-ambulatory individuals with sub-acute stroke stood on two force plates and initiated gait at a self-selected speed. Medio-lateral centre of pressure displacement was calculated and used to define anticipatory postural adjustments (shift in medio-lateral centre of pressure >10mm from baseline). Stroke severity, motor recovery, and functional balance and mobility status were also obtained. Three patterns were identified: single (typical), absent (atypical), and multiple (atypical) anticipatory postural adjustments. Thirty-five percent of trials had atypical anticipatory postural adjustments (absent and multiple). Frequency of absent anticipatory postural adjustments was negatively correlated with walking speed. Multiple anticipatory postural adjustments were more prevalent when leading with the non-paretic than the paretic limb. Trials with multiple anticipatory postural adjustments had longer duration of anticipatory postural adjustment and time to foot-off, and shorter unloading time than trials with single anticipatory postural adjustments. A high prevalence of atypical anticipatory control prior to gait initiation was found in individuals with stroke. Temporal differences were identified with multiple anticipatory postural adjustments, indicating altered gait initiation. These findings provide insight into postural control during gait initiation in individuals with sub-acute stroke, and may inform interventions to improve ambulation in this population. Copyright © 2016 Elsevier B.V. All rights reserved.

Distinct Effects of Trial-Driven and Task Set-Related Control in Primary Visual Cortex

PubMed Central

Vaden, Ryan J.; Visscher, Kristina M.

2015-01-01

Task sets are task-specific configurations of cognitive processes that facilitate task-appropriate reactions to stimuli. While it is established that the trial-by-trial deployment of visual attention to expected stimuli influences neural responses in primary visual cortex (V1) in a retinotopically specific manner, it is not clear whether the mechanisms that help maintain a task set over many trials also operate with similar retinotopic specificity. Here, we address this question by using BOLD fMRI to characterize how portions of V1 that are specialized for different eccentricities respond during distinct components of an attention-demanding discrimination task: cue-driven preparation for a trial, trial-driven processing, task-initiation at the beginning of a block of trials, and task-maintenance throughout a block of trials. Tasks required either unimodal attention to an auditory or a visual stimulus or selective intermodal attention to the visual or auditory component of simultaneously presented visual and auditory stimuli. We found that while the retinotopic patterns of trial-driven and cue-driven activity depended on the attended stimulus, the retinotopic patterns of task-initiation and task-maintenance activity did not. Further, only the retinotopic patterns of trial-driven activity were found to depend on the presence of intermodal distraction. Participants who performed well on the intermodal selective attention tasks showed strong task-specific modulations of both trial-driven and task-maintenance activity. Importantly, task-related modulations of trial-driven and task-maintenance activity were in opposite directions. Together, these results confirm that there are (at least) two different processes for top-down control of V1: One, working trial-by-trial, differently modulates activity across different eccentricity sectors—portions of V1 corresponding to different visual eccentricities. The second process works across longer epochs of task performance, and does not differ among eccentricity sectors. These results are discussed in the context of previous literature examining top-down control of visual cortical areas. PMID:26163806

Lessons learned: Infrastructure development and financial management for large, publicly funded, international trials.

PubMed

Larson, Gregg S; Carey, Cate; Grarup, Jesper; Hudson, Fleur; Sachi, Karen; Vjecha, Michael J; Gordin, Fred

2016-04-01

Randomized clinical trials are widely recognized as essential to address worldwide clinical and public health research questions. However, their size and duration can overwhelm available public and private resources. To remain competitive in international research settings, advocates and practitioners of clinical trials must implement practices that reduce their cost. We identify approaches and practices for large, publicly funded, international trials that reduce cost without compromising data integrity and recommend an approach to cost reporting that permits comparison of clinical trials. We describe the organizational and financial characteristics of The International Network for Strategic Initiatives in Global HIV Trials, an infectious disease research network that conducts multiple, large, long-term, international trials, and examine challenges associated with simple and streamlined governance and an infrastructure and financial management model that is based on performance, transparency, and accountability. It is possible to reduce costs of participants' follow-up and not compromise clinical trial quality or integrity. The International Network for Strategic Initiatives in Global HIV Trials network has successfully completed three large HIV trials using cost-efficient practices that have not adversely affected investigator enthusiasm, accrual rates, loss-to-follow-up, adherence to the protocol, and completion of data collection. This experience is relevant to the conduct of large, publicly funded trials in other disease areas, particularly trials dependent on international collaborations. New approaches, or creative adaption of traditional clinical trial infrastructure and financial management tools, can render large, international clinical trials more cost-efficient by emphasizing structural simplicity, minimal up-front costs, payments for performance, and uniform algorithms and fees-for-service, irrespective of location. However, challenges remain. They include institutional resistance to financial change, growing trial complexity, and the difficulty of sustaining network infrastructure absent stable research work. There is also a need for more central monitoring, improved and harmonized regulations, and a widely applied metric for measuring and comparing cost efficiency in clinical trials. ClinicalTrials.gov is recommended as a location where standardized trial cost information could be made publicly accessible. © The Author(s) 2016.

An Evaluation of the Effectiveness of Recruitment Methods: The Staying Well after Depression Randomized Controlled Trial

PubMed Central

Krusche, Adele; Rudolf von Rohr, Isabelle; Muse, Kate; Duggan, Danielle; Crane, Catherine; Williams, J. Mark G.

2014-01-01

Background Randomized controlled trials (RCTs) are widely accepted as being the most efficient way of investigating the efficacy of psychological therapies. However, researchers conducting RCTs commonly report difficulties recruiting an adequate sample within planned timescales. In an effort to overcome recruitment difficulties, researchers often are forced to expand their recruitment criteria or extend the recruitment phase, thus increasing costs and delaying publication of results. Research investigating the effectiveness of recruitment strategies is limited and trials often fail to report sufficient details about the recruitment sources and resources utilised. Purpose We examined the efficacy of strategies implemented during the Staying Well after Depression RCT in Oxford to recruit participants with a history of recurrent depression. Methods We describe eight recruitment methods utilised and two further sources not initiated by the research team and examine their efficacy in terms of (i) the return, including the number of potential participants who contacted the trial and the number who were randomized into the trial, (ii) cost-effectiveness, comprising direct financial cost and manpower for initial contacts and randomized participants, and (iii) comparison of sociodemographic characteristics of individuals recruited from different sources. Results Poster advertising, web-based advertising and mental health worker referrals were the cheapest methods per randomized participant; however, the ratio of randomized participants to initial contacts differed markedly per source. Advertising online, via posters and on a local radio station were the most cost-effective recruitment methods for soliciting participants who subsequently were randomized into the trial. Advertising across many sources (saturation) was found to be important. Limitations It may not be feasible to employ all the recruitment methods used in this trial to obtain participation from other populations, such as those currently unwell, or in other geographical locations. Recruitment source was unavailable for participants who could not be reached after the initial contact. Thus, it is possible that the efficiency of certain methods of recruitment was poorer than estimated. Efficacy and costs of other recruitment initiatives, such as providing travel expenses to the in-person eligibility assessment and making follow-up telephone calls to candidates who contacted the recruitment team but could not be screened promptly, were not analysed. Conclusions Website advertising resulted in the highest number of randomized participants and was the second cheapest method of recruiting. Future research should evaluate the effectiveness of recruitment strategies for other samples to contribute to a comprehensive base of knowledge for future RCTs. PMID:24686105

An evaluation of the effectiveness of recruitment methods: the staying well after depression randomized controlled trial.

PubMed

Krusche, Adele; Rudolf von Rohr, Isabelle; Muse, Kate; Duggan, Danielle; Crane, Catherine; Williams, J Mark G

2014-04-01

Randomized controlled trials (RCTs) are widely accepted as being the most efficient way of investigating the efficacy of psychological therapies. However, researchers conducting RCTs commonly report difficulties in recruiting an adequate sample within planned timescales. In an effort to overcome recruitment difficulties, researchers often are forced to expand their recruitment criteria or extend the recruitment phase, thus increasing costs and delaying publication of results. Research investigating the effectiveness of recruitment strategies is limited, and trials often fail to report sufficient details about the recruitment sources and resources utilized. We examined the efficacy of strategies implemented during the Staying Well after Depression RCT in Oxford to recruit participants with a history of recurrent depression. We describe eight recruitment methods utilized and two further sources not initiated by the research team and examine their efficacy in terms of (1) the return, including the number of potential participants who contacted the trial and the number who were randomized into the trial; (2) cost-effectiveness, comprising direct financial cost and manpower for initial contacts and randomized participants; and (3) comparison of sociodemographic characteristics of individuals recruited from different sources. Poster advertising, web-based advertising, and mental health worker referrals were the cheapest methods per randomized participant; however, the ratio of randomized participants to initial contacts differed markedly per source. Advertising online, via posters, and on a local radio station were the most cost-effective recruitment methods for soliciting participants who subsequently were randomized into the trial. Advertising across many sources (saturation) was found to be important. It may not be feasible to employ all the recruitment methods used in this trial to obtain participation from other populations, such as those currently unwell, or in other geographical locations. Recruitment source was unavailable for participants who could not be reached after the initial contact. Thus, it is possible that the efficiency of certain methods of recruitment was poorer than estimated. Efficacy and costs of other recruitment initiatives, such as providing travel expenses to the in-person eligibility assessment and making follow-up telephone calls to candidates who contacted the recruitment team but could not be screened promptly, were not analysed. Website advertising resulted in the highest number of randomized participants and was the second cheapest method of recruiting. Future research should evaluate the effectiveness of recruitment strategies for other samples to contribute to a comprehensive base of knowledge for future RCTs.

Soil fumigation to control spread of Fomes annosus: results of field trials

Treesearch

David R. Houston

1975-01-01

A field trial was run to test the hypothesis that a band of roots killed by soil fumigation with methyl bromide would be unsuitable for invasion by F. annosus and would block the underground spread of the fungus from diseased trees to healthy trees. Infection centers in red pine plantations from New York to Rhode Island were delineated on the basis...

Social Effects on Rat Spatial Choice in an Open Field Task

ERIC Educational Resources Information Center

Keller, Matthew R.; Brown, Michael F.

2011-01-01

Pairs of rats foraged in trials either together or separately in an open field apparatus for pellets hidden in discreet locations in a 5 x 5 matrix. Trial duration was either 1 or 4 min. The tendency to choose locations that had earlier been visited by another rat was examined by comparing the choices made in the presence and absence of the other…

Rimonabant Sanofi-Synthélabo.

PubMed

Fernandez, Jose R; Allison, David B

2004-04-01

Rimonabant, an antagonist of central cannabinoid type 1 (CB1) receptors, is being developed by Sanofi-Synthélabo for the potential treatment of obesity and as a potential smoking cessation agent. Phase III trials were initiated for obesity in August 2001 and were ongoing in September 2003. By September 2002, the compound had entered phase III trials for smoking cessation, and these trials were ongoing in September 2003.

Design and implementation of a fault-tolerant and dynamic metadata database for clinical trials

NASA Astrophysics Data System (ADS)

Lee, J.; Zhou, Z.; Talini, E.; Documet, J.; Liu, B.

2007-03-01

In recent imaging-based clinical trials, quantitative image analysis (QIA) and computer-aided diagnosis (CAD) methods are increasing in productivity due to higher resolution imaging capabilities. A radiology core doing clinical trials have been analyzing more treatment methods and there is a growing quantity of metadata that need to be stored and managed. These radiology centers are also collaborating with many off-site imaging field sites and need a way to communicate metadata between one another in a secure infrastructure. Our solution is to implement a data storage grid with a fault-tolerant and dynamic metadata database design to unify metadata from different clinical trial experiments and field sites. Although metadata from images follow the DICOM standard, clinical trials also produce metadata specific to regions-of-interest and quantitative image analysis. We have implemented a data access and integration (DAI) server layer where multiple field sites can access multiple metadata databases in the data grid through a single web-based grid service. The centralization of metadata database management simplifies the task of adding new databases into the grid and also decreases the risk of configuration errors seen in peer-to-peer grids. In this paper, we address the design and implementation of a data grid metadata storage that has fault-tolerance and dynamic integration for imaging-based clinical trials.

77 FR 49409 - Oral Rabies Vaccine Trial; Availability of an Environmental Assessment and Finding of No...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-16

...] Oral Rabies Vaccine Trial; Availability of an Environmental Assessment and Finding of No Significant... assessment and finding of no significant impact relative to an oral rabies vaccination field trial in New... be prepared. FOR FURTHER INFORMATION CONTACT: Mr. Richard Chipman, Rabies Program Coordinator...

78 FR 33798 - Oral Rabies Vaccine Trial; Availability of a Supplemental Environmental Assessment

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-05

... Inspection Service [Docket No. APHIS-2013-0046] Oral Rabies Vaccine Trial; Availability of a Supplemental... Inspection Service has prepared a supplemental environmental assessment (EA) relative to an oral rabies... analyzes expanding the field trial for an experimental oral rabies vaccine for wildlife to additional areas...

Effect of Breastfeeding Promotion on Early Childhood Caries and Breastfeeding Duration among 5 Year Old Children in Eastern Uganda: A Cluster Randomized Trial

PubMed Central

Birungi, Nancy; Fadnes, Lars T.; Okullo, Isaac; Kasangaki, Arabat; Nankabirwa, Victoria; Ndeezi, Grace; Tumwine, James K.; Tylleskär, Thorkild; Lie, Stein Atle; Åstrøm, Anne Nordrehaug

2015-01-01

Background Although several studies have shown short term health benefits of exclusive breastfeeding (EBF), its long term consequences have not been studied extensively in low-income contexts. This study assessed the impact of an EBF promotion initiative for 6 months on early childhood caries (ECC) and breastfeeding duration in children aged 5 years in Mbale, Eastern Uganda. Methods Participants were recruited from the Ugandan site of the PROMISE- EBF cluster randomised trial (ClinicalTrials.gov no: NCT00397150). A total of 765 pregnant women from 24 clusters were included in the ratio 1:1 to receive peer counselled promotion of EBF as the intervention or standard of care. At the 5 year follow-up, ECC was recorded under field conditions using the World Health Organization’s decayed missing filled tooth (dmft) index. Adjusted negative binomial and linear regression were used in the analysis. Results Mean breastfeeding duration in the intervention and control groups (n=417) were 21.8 (CI 20.7–22.9) and 21.3(CI 20.7–21.9) months, respectively. The mean dmft was 1.5 (standard deviation [SD] 2.9) and 1.7 (SD 2.9) in the intervention and control groups, respectively. Corresponding prevalence estimates of ECC were 38% and 41%. Negative binomial regression analysis adjusted for cluster effects and loss-to-follow-up by inverse probability weights (IPW) showed an incidence-rate ratio (IRR) of 0.91 (95% CI 0.65–1.2). Comparing the effect of the trial arm on breastfeeding duration showed a difference in months of 0.48 (-0.72 to 1.7). Conclusion PROMISE EBF trial did not impact on early childhood caries or breastfeeding duration at 5 years of age. This study contributes to the body of evidence that promotion of exclusive breastfeeding does not raise oral health concerns. However, the high burden of caries calls for efforts to improve the oral health condition in this setting. Trial Registration ClinicalTrials.gov NCT00397150 PMID:25938681

An integrated vegetated ditch system reduces chlorpyrifos loading in agricultural runoff.

PubMed

Phillips, Bryn M; Anderson, Brian S; Cahn, Michael; Rego, Jessa L; Voorhees, Jennifer P; Siegler, Katie; Zhang, Xuyang; Budd, Robert; Goh, Kean; Tjeerdema, Ron S

2017-03-01

Agricultural runoff containing toxic concentrations of the organophosphate pesticide chlorpyrifos has led to impaired water body listings and total maximum daily load restrictions in California's central coast watersheds. Chlorpyrifos use is now tightly regulated by the Central Coast Regional Water Quality Control Board. This study evaluated treatments designed to reduce chlorpyrifos in agricultural runoff. Initial trials evaluated the efficacy of 3 different drainage ditch installations individually: compost filters, granulated activated carbon (GAC) filters, and native grasses in a vegetated ditch. Treatments were compared to bare ditch controls, and experiments were conducted with simulated runoff spiked with chlorpyrifos at a 1.9 L/s flow rate. Chlorpyrifos concentrations and toxicity to Ceriodaphnia dubia were measured at the input and output of the system. Input concentrations of chlorpyrifos ranged from 858 ng/L to 2840 ng/L. Carbon filters and vegetation provided the greatest load reduction of chlorpyrifos (99% and 90%, respectively). Toxicity was completely removed in only one of the carbon filter trials. A second set of trials evaluated an integrated approach combining all 3 treatments. Three trials were conducted each at 3.2 L/s and 6.3 L/s flow rates at input concentrations ranging from 282 ng/L to 973 ng/L. Chlorpyrifos loadings were reduced by an average of 98% at the low flow rate and 94% at the high flow rate. Final chlorpyrifos concentrations ranged from nondetect (<50 ng/L) to 82 ng/L. Toxicity to C. dubia was eliminated in 3 of 6 integrated trials. Modeling of the ditch and its components informed design alterations that are intended to eventually remove up to 100% of pesticides and sediment. Future work includes investigating the adsorption capacity of GAC, costs associated with GAC disposal, and real-world field trials to further reduce model uncertainties and confirm design optimization. Trials with more water-soluble pesticides such as neonicotinoids are also recommended. Integr Environ Assess Manag 2017;13:423-430. © 2016 SETAC. © 2016 SETAC.

Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial.

PubMed

Coghlan, John Gerry; Galiè, Nazzareno; Barberà, Joan Albert; Frost, Adaani E; Ghofrani, Hossein-Ardeschir; Hoeper, Marius M; Kuwana, Masataka; McLaughlin, Vallerie V; Peacock, Andrew J; Simonneau, Gérald; Vachiéry, Jean-Luc; Blair, Christiana; Gillies, Hunter; Miller, Karen L; Harris, Julia H N; Langley, Jonathan; Rubin, Lewis J

2017-07-01

Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), in particular systemic sclerosis (SSc), had an attenuated response compared with idiopathic PAH in most trials. Thus, there is uncertainty regarding the benefit of PAH-targeted therapy in some forms of CTD-PAH. To explore the safety and efficacy of initial combination therapy with ambrisentan and tadalafil versus ambrisentan or tadalafil monotherapy in patients with CTD-PAH and SSc-PAH enrolled in the AMBITION trial. This was a post hoc analysis of patients with CTD-PAH and SSc-PAH from AMBITION, an event-driven, double-blind trial in patients with WHO functional class II/III PAH. Treatment-naive patients were randomised 2:1:1 to once-daily initial combination therapy with ambrisentan plus tadalafil or monotherapy with ambrisentan or tadalafil, respectively. The primary endpoint was time to the first clinical failure event (first occurrence of death, hospitalisation for worsening PAH, disease progression or unsatisfactory long-term clinical response). In the primary analysis set (N=500), 187 patients had CTD-PAH, of whom 118 had SSc-PAH. Initial combination therapy reduced the risk of clinical failure versus pooled monotherapy in each subgroup: CTD-PAH (HR 0.43 (95% CI 0.24 to 0.77)) and SSc-PAH (0.44 (0.22 to 0.89)). The most common AE was peripheral oedema, which was reported more frequently with initial combination therapy than monotherapy in the two PAH subgroups. The relative frequency of adverse events between those on combination therapy versus monotherapy was similar across subgroups. This post hoc subgroup analysis provides evidence that CTD-PAH and SSc-PAH patients benefit from initial ambrisentan and tadalafil combination therapy. NCT01178073, post results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Latest developments in MUC1 immunotherapy.

PubMed

Taylor-Papadimitriou, Joyce; Burchell, Joy M; Graham, Rosalind; Beatson, Richard

2018-05-21

Currently, there is renewed interest in attempting to recruit the host immune system to eliminate cancers, and within this renewed activity, MUC1 continues to arouse interest. MUC1 has been considered a possible therapeutic target for the past 30 years as it is up-regulated, aberrantly glycosylated and its polarization is lost in many adenocarcinomas. Moreover, MUC1 is expressed by some haematopoietic cancers, including acute myeloid leukaemia and myeloma. Although multiple clinical trials have been initiated and immune responses have been documented, effective clinical benefit worthy of approval for general application has not as yet been achieved. However, this does not appear to have quelled the interest in MUC1 as a therapeutic target, as shown by the increase in the number of MUC1-based clinical trials initiated in 2017 ( Figure 1). As with all translational studies, incorporating new relevant research findings into therapeutic strategy is difficult. Decisions are made to commit to a specific strategy based on the information and data available when the trial is initiated. However, the time required for preclinical studies and early trials can render the founding concept not always appropriate for proceeding to a larger definitive trial. Here, we summarize the attempts made, to date, to bring MUC1 into the world of cancer immunotherapy and discuss how research findings regarding MUC1 structure and function together with expanded knowledge of its interactions with the tumour environment and immune effector cells could lead to improved therapeutic approaches. © 2018 The Author(s).

Retention of the "first-trial effect" in gait-slip among community-living older adults.

PubMed

Liu, Xuan; Bhatt, Tanvi; Wang, Shuaijie; Yang, Feng; Pai, Yi-Chung Clive

2017-02-01

"First-trial effect" characterizes the rapid adaptive behavior that changes the performance outcome (from fall to non-fall) after merely a single exposure to postural disturbance. The purpose of this study was to investigate how long the first-trial effect could last. Seventy-five (≥ 65 years) community-dwelling older adults, who were protected by an overhead full body harness system, were retested for a single slip 6-12 months after their initial exposure to a single gait-slip. Subjects' body kinematics that was used to compute their proactive (feedforward) and reactive (feedback) control of stability was recorded by an eight-camera motion analysis system. We found the laboratory falls of subjects on their retest slip were significantly lower than that on the novel initial slip, and the reactive stability of these subjects was also significantly improved. However, the proactive stability of subjects remains unchanged between their initial slip and retest slip. The fall rates and stability control had no difference among the 6-, 9-, and 12-month retest groups, which indicated a maximum retention on 12 months after a single slip in the laboratory. These results highlighted the importance of the "first-trial effect" and suggested that perturbation training is effective for fall prevention, with lower trial doses for a long period (up to 1 year). Therefore, single slip training might benefit those older adults who could not tolerate larger doses in reality.

Field-scale multi-phase LNAPL remediation: Validating a new computational framework against sequential field pilot trials.

PubMed

Sookhak Lari, Kaveh; Johnston, Colin D; Rayner, John L; Davis, Greg B

2018-03-05

Remediation of subsurface systems, including groundwater, soil and soil gas, contaminated with light non-aqueous phase liquids (LNAPLs) is challenging. Field-scale pilot trials of multi-phase remediation were undertaken at a site to determine the effectiveness of recovery options. Sequential LNAPL skimming and vacuum-enhanced skimming, with and without water table drawdown were trialled over 78days; in total extracting over 5m 3 of LNAPL. For the first time, a multi-component simulation framework (including the multi-phase multi-component code TMVOC-MP and processing codes) was developed and applied to simulate the broad range of multi-phase remediation and recovery methods used in the field trials. This framework was validated against the sequential pilot trials by comparing predicted and measured LNAPL mass removal rates and compositional changes. The framework was tested on both a Cray supercomputer and a cluster. Simulations mimicked trends in LNAPL recovery rates (from 0.14 to 3mL/s) across all remediation techniques each operating over periods of 4-14days over the 78day trial. The code also approximated order of magnitude compositional changes of hazardous chemical concentrations in extracted gas during vacuum-enhanced recovery. The verified framework enables longer term prediction of the effectiveness of remediation approaches allowing better determination of remediation endpoints and long-term risks. Copyright © 2017 Commonwealth Scientific and Industrial Research Organisation. Published by Elsevier B.V. All rights reserved.

Legal and ethical obligations to conduct a clinical drug trial in Australia as an investigator initiated and sponsored study for an overseas pharmaceutical company.

PubMed

Beran, Roy G

2004-01-01

Most multi-centre trials are both financed and sponsored by the pharmaceutical company involved. What follows will map the path adopted for an investigator initiated and sponsored study for a new indication of an established medication. The chief investigators of a company-sponsored, investigator-initiated, multi-centre, placebo-controlled study of an established medication, Pharmaceutical Benefit Scheme (PBS) listed for treatment of one condition but trialled in the management of another condition (trial of off-label use), were approached to submit a protocol to repeat the type of study with a different compound. The new study would test a different agent, also PBS listed, for the same condition as in the initial study and with the same off-licence application. The company would finance the study, provide the medication and matched placebo but only review the investigator-initiated protocol which would be sponsored by the principal investigator. This required the investigator to implement the trial, as would normally be done by the pharmaceutical company, yet also act as its principal investigator. The principal investigator, with colleagues and a Clinical Research Organisation (CRO), developed a protocol, adapted for the new agent, and submitted it for approval. Upon acceptance a contract was negotiated with the pharmaceutical company which had to overcome jurisdictional conflicts between common law and civil law legal systems. A CRO was contracted to undertake administrative functions which dictated special contractual agreements to overcome possible conflicts of interest for a sponsor/investigator to protect patient interests. There was need to find indemnification insurance with jurisdictional problems, co-investigators, ethics committee approvals and finance management as just some of the difficulties encountered. The paper will outline how these obstacles were overcome and how ethical and legal issues were respected through compromise. The ethical and legal obligations were addressed in a fashion which allowed the conduct of a trial adopting a proven methodology but novel infrastructure such that it was a totally independent study with regards conduct and reporting of final data, irrespective of the results being either positive or negative. This may represent a more acceptable way to ensure that future clinical trials are devoid of undue influence from the pharmaceutical industry which may still fund the study.

Government regulation and public opposition create high additional costs for field trials with GM crops in Switzerland.

PubMed

Bernauer, Thomas; Tribaldos, Theresa; Luginbühl, Carolin; Winzeler, Michael

2011-12-01

Field trials with GM crops are not only plant science experiments. They are also social experiments concerning the implications of government imposed regulatory constraints and public opposition for scientific activity. We assess these implications by estimating additional costs due to government regulation and public opposition in a recent set of field trials in Switzerland. We find that for every Euro spent on research, an additional 78 cents were spent on security, an additional 31 cents on biosafety, and an additional 17 cents on government regulatory supervision. Hence the total additional spending due to government regulation and public opposition was around 1.26 Euros for every Euro spent on the research per se. These estimates are conservative; they do not include additional costs that are hard to monetize (e.g. stakeholder information and dialogue activities, involvement of various government agencies). We conclude that further field experiments with GM crops in Switzerland are unlikely unless protected sites are set up to reduce these additional costs.