A methodology for assessing the effect of correlations among muscle synergy activations on task-discriminating information.

PubMed

Delis, Ioannis; Berret, Bastien; Pozzo, Thierry; Panzeri, Stefano

2013-01-01

Muscle synergies have been hypothesized to be the building blocks used by the central nervous system to generate movement. According to this hypothesis, the accomplishment of various motor tasks relies on the ability of the motor system to recruit a small set of synergies on a single-trial basis and combine them in a task-dependent manner. It is conceivable that this requires a fine tuning of the trial-to-trial relationships between the synergy activations. Here we develop an analytical methodology to address the nature and functional role of trial-to-trial correlations between synergy activations, which is designed to help to better understand how these correlations may contribute to generating appropriate motor behavior. The algorithm we propose first divides correlations between muscle synergies into types (noise correlations, quantifying the trial-to-trial covariations of synergy activations at fixed task, and signal correlations, quantifying the similarity of task tuning of the trial-averaged activation coefficients of different synergies), and then uses single-trial methods (task-decoding and information theory) to quantify their overall effect on the task-discriminating information carried by muscle synergy activations. We apply the method to both synchronous and time-varying synergies and exemplify it on electromyographic data recorded during performance of reaching movements in different directions. Our method reveals the robust presence of information-enhancing patterns of signal and noise correlations among pairs of synchronous synergies, and shows that they enhance by 9-15% (depending on the set of tasks) the task-discriminating information provided by the synergy decompositions. We suggest that the proposed methodology could be useful for assessing whether single-trial activations of one synergy depend on activations of other synergies and quantifying the effect of such dependences on the task-to-task differences in muscle activation patterns.

A single-blind trial of reflexology for irritable bowel syndrome.

PubMed Central

Tovey, Philip

2002-01-01

BACKGROUND: Irritable bowel syndrome (IBS) is a significant problem for primary care, as treatment options are limited and it can frequently develop into a chronic condition. Complementary and alternative medicine, including reflexology, is being turned to increasingly in an attempt to manage symptoms. There are currently no studies which address the effectiveness of reflexology for IBS. Despite this, it continues to be advocated and used. AIM: To provide the first evidence on the effectiveness of reflexology in the management of the core defining symptoms of IBS. DESIGN OF STUDY: A single-blind trial carried out in primary care settings. SETTING: Thirty-four participants diagnosed with IBS on the basis of the Rome Criteria. METHOD: Participants were allocated to receive either a reflexology foot massage or a non-reflexology foot massage control group. RESULTS: On none of the three symptoms monitored--abdominal pain, constipation/diarrhoea, and abdominal distention--was there a statistically or clinically significant difference between reflexology and control groups. CONCLUSION: On the basis of these results there is nothing to suggest that reflexology produces any specific benefit for patients with IBS. There is currently no evidence to support its use. However this was one (relatively) small scale study; further research that, for example, assesses the impact of therapist (professional and lay) versus therapy, is still needed. PMID:11791811

A unified procedure for meta-analytic evaluation of surrogate end points in randomized clinical trials

PubMed Central

Dai, James Y.; Hughes, James P.

2012-01-01

The meta-analytic approach to evaluating surrogate end points assesses the predictiveness of treatment effect on the surrogate toward treatment effect on the clinical end point based on multiple clinical trials. Definition and estimation of the correlation of treatment effects were developed in linear mixed models and later extended to binary or failure time outcomes on a case-by-case basis. In a general regression setting that covers nonnormal outcomes, we discuss in this paper several metrics that are useful in the meta-analytic evaluation of surrogacy. We propose a unified 3-step procedure to assess these metrics in settings with binary end points, time-to-event outcomes, or repeated measures. First, the joint distribution of estimated treatment effects is ascertained by an estimating equation approach; second, the restricted maximum likelihood method is used to estimate the means and the variance components of the random treatment effects; finally, confidence intervals are constructed by a parametric bootstrap procedure. The proposed method is evaluated by simulations and applications to 2 clinical trials. PMID:22394448

An automated diagnostic process (PDA) in clinical psychopharmacology. An exemplification of its use in a sulpiride versus haloperidol comparative trial.

PubMed

Castrogiovanni, P; Cassano, G B; Conti, L; Maggini, C; Bonollo, L; Sarteschi, P

1976-01-01

One of the main unsolved problems, and one which produces divergent results in clinical psychopharmacology, is that concerning the selection of patients and their diagnostic definition. An automated diagnostic procedure (PDA) was set up in order to classify each patient into one nosographic category on the basis of a cross-sectional examination of his mental state. Such diagnostic procedure appears particularly suitable for multicenter drug trials, since it gives a profile and a diagnostic definition of patients, assessed by investigators from different areas and with different cultural, and clinical backgrounds. In a multicenter trial (sulpiride versus haloperidol) PDA offered a chance to re-examine and analyze the characteristics of each patient and therefore to control the criteria followed for the sample selection in the various experimental settings. The agreement between clinician and computer diagnosis was 78.9%; this agreement rises to 85.5% if the computerlabelled schizo-affective syndromes are considered within the schizophrenic group. Moreover, and attempt has been made to relate psychopathological patterns to drug responses.

Ethical and regulatory issues of pragmatic cluster randomized trials in contemporary health systems

PubMed Central

Anderson, Monique L; Califf, Robert M; Sugarman, Jeremy

2015-01-01

Cluster randomized trials (CRTs) randomly assign groups of individuals to examine research questions or test interventions and measure their effects on individuals. Recent emphasis on quality improvement, comparative effectiveness, and learning health systems has prompted expanded use of pragmatic CRTs in routine healthcare settings, which in turn poses practical and ethical challenges that current oversight frameworks may not adequately address. The 2012 Ottawa Statement provides a basis for considering many issues related to pragmatic CRTs but challenges remain, including some arising from the current U.S. research and healthcare regulations. In order to examine the ethical, regulatory, and practical questions facing pragmatic CRTs in healthcare settings, the National Institutes of Health (NIH) Health Care Systems Research Collaboratory convened a workshop in Bethesda, Maryland in July of 2013. Attendees included experts in clinical trials, patient advocacy, research ethics, and research regulations from academia, industry, the NIH, and other federal agencies. Workshop participants identified substantial barriers to implementing these types of CRTs, including issues related to research design, gatekeepers and governance in health systems, consent, institutional review boards, data monitoring, privacy, and special populations. We describe these barriers and suggest means for understanding and overcoming them to facilitate pragmatic CRTs in healthcare settings. PMID:25733677

Alternatives for discounting in the analysis of noninferiority trials.

PubMed

Snapinn, Steven M

2004-05-01

Determining the efficacy of an experimental therapy relative to placebo on the basis of an active-control noninferiority trial requires reference to historical placebo-controlled trials. The validity of the resulting comparison depends on two key assumptions: assay sensitivity and constancy. Since the truth of these assumptions cannot be verified, it seems logical to raise the standard of evidence required to declare efficacy; this concept is referred to as discounting. It is not often recognized that two common design and analysis approaches, setting a noninferiority margin and requiring preservation of a fraction of the standard therapy's effect, are forms of discounting. The noninferiority margin is a particularly poor approach, since its degree of discounting depends on an irrelevant factor. Preservation of effect is more reasonable, but it addresses only the constancy assumption, not the issue of assay sensitivity. Gaining consensus on the most appropriate approach to the design and analysis of noninferiority trials will require a common understanding of the concept of discounting.

Shared motion signals for human perceptual decisions and oculomotor actions

NASA Technical Reports Server (NTRS)

Stone, Leland S.; Krauzlis, Richard J.

2003-01-01

A fundamental question in primate neurobiology is to understand to what extent motor behaviors are driven by shared neural signals that also support conscious perception or by independent subconscious neural signals dedicated to motor control. Although it has clearly been established that cortical areas involved in processing visual motion support both perception and smooth pursuit eye movements, it remains unknown whether the same or different sets of neurons within these structures perform these two functions. Examination of the trial-by-trial variation in human perceptual and pursuit responses during a simultaneous psychophysical and oculomotor task reveals that the direction signals for pursuit and perception are not only similar on average but also co-vary on a trial-by-trial basis, even when performance is at or near chance and the decisions are determined largely by neural noise. We conclude that the neural signal encoding the direction of target motion that drives steady-state pursuit and supports concurrent perceptual judgments emanates from a shared ensemble of cortical neurons.

Cue-type manipulation dissociates two types of task set inhibition: backward inhibition and competitor rule suppression.

PubMed

Regev, Shirley; Meiran, Nachshon

2016-07-01

Backward inhibition (BI) reflects the suppression of a recently abandoned task set to allow for smooth transition to a new task even when the rules do not generate a response conflict. Competitor rule suppression (CRS) reflects the inhibition/suppression of irrelevant task rules when these rules generate a response conflict even if they have not recently been abandoned. We assessed whether BI and CRS are differentially affected by the difficulty in retrieving category-response mappings from memory. Retrieval demands were manipulated via the information provided by the task cues, which either indicated the relevant dimension (dimension cues; "color") or the relevant dimension with its category-to-key mapping (mapping cues; "red green", indicating that "red" and "green" go with the left/right responses, respectively). CRS was larger with dimension compared to mapping cues when cue-type varied between groups and was larger after trials involving dimension cues when cue-type varied on a trial-by-trial basis. In contrast, BI was not influenced by cue-type. These results suggest that task switching involve at least two distinct inhibitory processes, with CRS being related to the ease of retrieval of category-response mappings from memory.

The limitations of using randomised controlled trials as a basis for developing treatment guidelines.

PubMed

Mulder, Roger; Singh, Ajeet B; Hamilton, Amber; Das, Pritha; Outhred, Tim; Morris, Grace; Bassett, Darryl; Baune, Bernhard T; Berk, Michael; Boyce, Philip; Lyndon, Bill; Parker, Gordon; Malhi, Gin S

2018-02-01

Randomised controlled trials (RCTs) are considered the 'gold standard' by which novel psychotropic medications and psychological interventions are evaluated and consequently adopted into widespread clinical practice. However, there are some limitations to using RCTs as the basis for developing treatment guidelines. While RCTs allow researchers to determine whether a given medication or intervention is effective in a specific patient sample, for practicing clinicians it is more important to know whether it will work for their particular patient in their particular setting. This information cannot be garnered from an RCT. These inherent limitations are exacerbated by biases in design, recruitment, sample populations and data analysis that are inevitable in real-world studies. While trial registration and CONSORT have been implemented to correct and improve these issues, it is worrying that many trials fail to achieve such standards and yet their findings are used to inform clinical decision making. This perspective piece questions the assumptions of RCTs and highlights the widespread distortion of findings that currently undermine the credibility of this powerful design. It is recommended that the clinical guidelines include advice as to what should be considered good and relevant evidence and that external bodies continue to monitor RCTs to ensure that the outcomes published indeed reflect reality. © 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.

Patient representatives' views on patient information in clinical cancer trials.

PubMed

Dellson, Pia; Nilbert, Mef; Carlsson, Christina

2016-02-01

Patient enrolment into clinical trials is based on oral information and informed consent, which includes an information sheet and a consent certificate. The written information should be complete, but at the same time risks being so complex that it may be questioned if a fully informed consent is possible to provide. We explored patient representatives' views and perceptions on the written trial information used in clinical cancer trials. Written patient information leaflets used in four clinical trials for colorectal cancer were used for the study. The trials included phase I-III trials, randomized and non-randomized trials that evaluated chemotherapy/targeted therapy in the neoadjuvant, adjuvant and palliative settings. Data were collected through focus groups and were analysed using inductive content analysis. Two major themes emerged: emotional responses and cognitive responses. Subthemes related to the former included individual preferences and perceptions of effect, while subthemes related to the latter were comprehensibility and layout. Based on these observations the patient representatives provided suggestions for improvement, which largely included development of future simplified and more attractive informed consent forms. The emotional and cognitive responses to written patient information reported by patient representatives provides a basis for revised formats in future trials and add to the body of information that support use of plain language, structured text and illustrations to improve the informed consent process and thereby patient enrolment into clinical trials.

Attention has memory: priming for the size of the attentional focus.

PubMed

Fuggetta, Giorgio; Lanfranchi, Silvia; Campana, Gianluca

2009-01-01

Repeating the same target's features or spatial position, as well as repeating the same context (e.g. distractor sets) in visual search leads to a decrease of reaction times. This modulation can occur on a trial by trial basis (the previous trial primes the following one), but can also occur across multiple trials (i.e. performance in the current trial can benefit from features, position or context seen several trials earlier), and includes inhibition of different features, position or contexts besides facilitation of the same ones. Here we asked whether a similar implicit memory mechanism exists for the size of the attentional focus. By manipulating the size of the attentional focus with the repetition of search arrays with the same vs. different size, we found both facilitation for the same array size and inhibition for a different array size, as well as a progressive improvement in performance with increasing the number of repetition of search arrays with the same size. These results show that implicit memory for the size of the attentional focus can guide visual search even in the absence of feature or position priming, or distractor's contextual effects.

Potential Representation - Global vs. Local Trial Functions

NASA Astrophysics Data System (ADS)

Michel, Volker

2014-05-01

Many systems of trial functions are available for representing potential fields on the sphere or parts of the sphere. We distinguish global trial functions (such as spherical harmonics) from localized trial functions (such as spline basis functions, scaling functions, wavelets, and Slepian functions). All these systems have their own pros and cons. We discuss the advantages and disadvantages of several selected systems of trial functions and propose criteria for their applicability. Moreover, we present an algorithm which is able to combine different types of trial functions. This yields a sparser solution which combines the features of the different basis systems which are used.

Harmonized clinical trial methodologies for localized cutaneous leishmaniasis and potential for extensive network with capacities for clinical evaluation

PubMed Central

Grogl, Max; Boni, Marina; Carvalho, Edgar M.; Chebli, Houda; Cisse, Mamoudou; Diro, Ermias; Fernandes Cota, Gláucia; Erber, Astrid C.; Gadisa, Endalamaw; Handjani, Farhad; Khamesipour, Ali; Llanos-Cuentas, Alejandro; López Carvajal, Liliana; Grout, Lise; Lmimouni, Badre Eddine; Mokni, Mourad; Nahzat, Mohammad Sami; Ben Salah, Afif; Ozbel, Yusuf; Pascale, Juan Miguel; Rizzo Molina, Nidia; Rode, Joelle; Romero, Gustavo; Ruiz-Postigo, José Antonio; Gore Saravia, Nancy; Soto, Jaime; Uzun, Soner; Mashayekhi, Vahid; Vélez, Ivan Dario; Vogt, Florian; Zerpa, Olga; Arana, Byron

2018-01-01

Introduction Progress with the treatment of cutaneous leishmaniasis (CL) has been hampered by inconsistent methodologies used to assess treatment effects. A sizable number of trials conducted over the years has generated only weak evidence backing current treatment recommendations, as shown by systematic reviews on old-world and new-world CL (OWCL and NWCL). Materials and methods Using a previously published guidance paper on CL treatment trial methodology as the reference, consensus was sought on key parameters including core eligibility and outcome measures, among OWCL (7 countries, 10 trial sites) and NWCL (7 countries, 11 trial sites) during two separate meetings. Results Findings and level of consensus within and between OWCL and NWCL sites are presented and discussed. In addition, CL trial site characteristics and capacities are summarized. Conclusions The consensus reached allows standardization of future clinical research across OWCL and NWCL sites. We encourage CL researchers to adopt and adapt as required the proposed parameters and outcomes in their future trials and provide feedback on their experience. The expertise afforded between the two sets of clinical sites provides the basis for a powerful consortium with potential for extensive, standardized assessment of interventions for CL and faster approval of candidate treatments. PMID:29329311

Temporal Expectations Guide Dynamic Prioritization in Visual Working Memory through Attenuated α Oscillations.

PubMed

van Ede, Freek; Niklaus, Marcel; Nobre, Anna C

2017-01-11

Although working memory is generally considered a highly dynamic mnemonic store, popular laboratory tasks used to understand its psychological and neural mechanisms (such as change detection and continuous reproduction) often remain relatively "static," involving the retention of a set number of items throughout a shared delay interval. In the current study, we investigated visual working memory in a more dynamic setting, and assessed the following: (1) whether internally guided temporal expectations can dynamically and reversibly prioritize individual mnemonic items at specific times at which they are deemed most relevant; and (2) the neural substrates that support such dynamic prioritization. Participants encoded two differently colored oriented bars into visual working memory to retrieve the orientation of one bar with a precision judgment when subsequently probed. To test for the flexible temporal control to access and retrieve remembered items, we manipulated the probability for each of the two bars to be probed over time, and recorded EEG in healthy human volunteers. Temporal expectations had a profound influence on working memory performance, leading to faster access times as well as more accurate orientation reproductions for items that were probed at expected times. Furthermore, this dynamic prioritization was associated with the temporally specific attenuation of contralateral α (8-14 Hz) oscillations that, moreover, predicted working memory access times on a trial-by-trial basis. We conclude that attentional prioritization in working memory can be dynamically steered by internally guided temporal expectations, and is supported by the attenuation of α oscillations in task-relevant sensory brain areas. In dynamic, everyday-like, environments, flexible goal-directed behavior requires that mental representations that are kept in an active (working memory) store are dynamic, too. We investigated working memory in a more dynamic setting than is conventional, and demonstrate that expectations about when mnemonic items are most relevant can dynamically and reversibly prioritize these items in time. Moreover, we uncover a neural substrate of such dynamic prioritization in contralateral visual brain areas and show that this substrate predicts working memory retrieval times on a trial-by-trial basis. This places the experimental study of working memory, and its neuronal underpinnings, in a more dynamic and ecologically valid context, and provides new insights into the neural implementation of attentional prioritization within working memory. Copyright © 2017 van Ede et al.

Role of scanning electron microscopy in identifying drugs used in medical practice.

PubMed

Fazil Marickar, Y M; Sylaja, N; Koshy, Peter

2009-10-01

Several plant preparations are administered for treatment of stone disease without scientific basis. This paper presents the results of in vitro and animal experimental studies using scanning electron microscopy (SEM) in the identification of the therapeutic properties of trial drugs in medicine. In the first set of the study, urinary crystals namely calcium oxalate monohydrate and calcium oxalate dehydrate were grown in six sets of Hane's tubes in silica gel medium. Trial drugs namely scoparia dulcis Lynn, musa sapiens and dolicos biflorus were incorporated in the gel medium to identify the dopant effect of the trial drugs on the size and extent of crystal column growth. The changes in morphology of crystals were studied using SEM. In the second set, six male Wistar rats each were calculogenised by administering sodium oxalate and ethylene glycol and diabetised using streptozotocin. The SEM changes of calculogenisation were studied. The rats were administered trial drugs before calculogenisation or after. The kidneys of the rats studied under the scanning electron microscope showed changes in tissue morphology and crystal deposition produced by calculogenisation and alterations produced by addition of trial drugs. The trial drugs produced changes in the pattern of crystal growth and in the crystal morphology of both calcium oxalate monohydrate and calcium oxalate dihydrate grown in vitro. Elemental distribution analysis showed that the crystal purity was not altered by the trial drugs. Scoparia dulcis Lynn was found to be the most effective anticalculogenic agent. Musa sapiens and dolicos biflorus were found to have no significant effect in inhibiting crystal growth. The kidneys of rats on calculogenisation showed different grades of crystals in the glomerulus and interstitial tissues, extrusion of the crystals into the tubular lumen, collodisation and tissue inflammatory cell infiltration. Scoparia dulcis Lynn exhibited maximum protector effect against the changes of calculogenisation. Musa sapiens and dolicos biflorus had only minimal effect in preventing crystal deposition, inflammatory cell infiltration and other changes of calculogenisation. SEM was found to be effective in assessing the effect of drugs on crystal growth morphology and tissue histology.

Protocol for a randomised controlled trial of a web-based healthy relationship tool and safety decision aid for women experiencing domestic violence (I-DECIDE).

PubMed

Hegarty, Kelsey; Tarzia, Laura; Murray, Elizabeth; Valpied, Jodie; Humphreys, Cathy; Taft, Angela; Gold, Lisa; Glass, Nancy

2015-08-01

Domestic violence is a serious problem affecting the health and wellbeing of women globally. Interventions in health care settings have primarily focused on screening and referral, however, women often may not disclose abuse to health practitioners. The internet offers a confidential space in which women can assess the health of their relationships and make a plan for safety and wellbeing for themselves and their children. This randomised controlled trial is testing the effectiveness of a web-based healthy relationship tool and safety decision aid (I-DECIDE). Based broadly on the IRIS trial in the United States, it has been adapted for the Australian context where it is conducted entirely online and uses the Psychosocial Readiness Model as the basis for the intervention. In this two arm, pragmatic randomised controlled trial, women who have experienced abuse or fear of a partner in the previous 6 months will be computer randomised to receive either the I-DECIDE website or a comparator website (basic relationship and safety advice). The intervention includes self-directed reflection exercises on their relationship, danger level, priority setting, and results in an individualised, tailored action plan. Primary self-reported outcomes are: self-efficacy (General Self-Efficacy Scale) immediately after completion, 6 and 12 months post-baseline; and depressive symptoms (Centre for Epidemiologic Studies Depression Scale, Revised, 6 and 12 months post-baseline). Secondary outcomes include mean number of helpful actions for safety and wellbeing, mean level of fear of partner and cost-effectiveness. This fully-automated trial will evaluate a web-based self-information, self-reflection and self-management tool for domestic violence. We hypothesise that the improvement in self-efficacy and mental health will be mediated by increased perceived support and awareness encouraging positive change. If shown to be effective, I-DECIDE could be easily incorporated into the community sector and health care settings, providing an alternative to formal services for women not ready or able to acknowledge abuse and access specialised services. Trial registered on 15(th) December 2014 with the Australian New Zealand Clinical Trials Registry ACTRN12614001306606.

Basis sets for the calculation of core-electron binding energies

NASA Astrophysics Data System (ADS)

Hanson-Heine, Magnus W. D.; George, Michael W.; Besley, Nicholas A.

2018-05-01

Core-electron binding energies (CEBEs) computed within a Δ self-consistent field approach require large basis sets to achieve convergence with respect to the basis set limit. It is shown that supplementing a basis set with basis functions from the corresponding basis set for the element with the next highest nuclear charge (Z + 1) provides basis sets that give CEBEs close to the basis set limit. This simple procedure provides relatively small basis sets that are well suited for calculations where the description of a core-ionised state is important, such as time-dependent density functional theory calculations of X-ray emission spectroscopy.

Improving patient recruitment to multicentre clinical trials: the case for employing a data manager in a district general hospital-based oncology centre.

PubMed

Street, A; Strong, J; Karp, S

2001-01-01

One of the most frequently cited reasons for poor recruitment to multicentre randomized clinical trials is the additional workload placed on clinical staff. We report the effect on patient recruitment of employing a data manager to support clinical staff in an English district general hospital (DGH). In addition, we explore the effect data managers have on the quality of data collected, proxied by the number of queries arising with the trial organizers. We estimate that the cost of employing a data manager on a full-time basis is 502 per patient recruited but may amount to 326 if the appointment is part-time. Data quality is high when full responsibility lies with a data manager but falls when responsibility is shared. Whether the costs of employing a data manager to recruit patients from a DGH are worth incurring depends on the value placed on the speed at which multicentre trials can be completed, how important it is to broaden the research base beyond the traditional setting of teaching hospitals, and the amount of evaluative data required.

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

Papajak, Ewa; Truhlar, Donald G.

We present sets of convergent, partially augmented basis set levels corresponding to subsets of the augmented “aug-cc-pV(n+d)Z” basis sets of Dunning and co-workers. We show that for many molecular properties a basis set fully augmented with diffuse functions is computationally expensive and almost always unnecessary. On the other hand, unaugmented cc-pV(n+d)Z basis sets are insufficient for many properties that require diffuse functions. Therefore, we propose using intermediate basis sets. We developed an efficient strategy for partial augmentation, and in this article, we test it and validate it. Sequentially deleting diffuse basis functions from the “aug” basis sets yields the “jul”,more » “jun”, “may”, “apr”, etc. basis sets. Tests of these basis sets for Møller-Plesset second-order perturbation theory (MP2) show the advantages of using these partially augmented basis sets and allow us to recommend which basis sets offer the best accuracy for a given number of basis functions for calculations on large systems. Similar truncations in the diffuse space can be performed for the aug-cc-pVxZ, aug-cc-pCVxZ, etc. basis sets.« less

Estimating the CCSD basis-set limit energy from small basis sets: basis-set extrapolations vs additivity schemes

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

Spackman, Peter R.; Karton, Amir, E-mail: amir.karton@uwa.edu.au

Coupled cluster calculations with all single and double excitations (CCSD) converge exceedingly slowly with the size of the one-particle basis set. We assess the performance of a number of approaches for obtaining CCSD correlation energies close to the complete basis-set limit in conjunction with relatively small DZ and TZ basis sets. These include global and system-dependent extrapolations based on the A + B/L{sup α} two-point extrapolation formula, and the well-known additivity approach that uses an MP2-based basis-set-correction term. We show that the basis set convergence rate can change dramatically between different systems(e.g.it is slower for molecules with polar bonds and/ormore » second-row elements). The system-dependent basis-set extrapolation scheme, in which unique basis-set extrapolation exponents for each system are obtained from lower-cost MP2 calculations, significantly accelerates the basis-set convergence relative to the global extrapolations. Nevertheless, we find that the simple MP2-based basis-set additivity scheme outperforms the extrapolation approaches. For example, the following root-mean-squared deviations are obtained for the 140 basis-set limit CCSD atomization energies in the W4-11 database: 9.1 (global extrapolation), 3.7 (system-dependent extrapolation), and 2.4 (additivity scheme) kJ mol{sup –1}. The CCSD energy in these approximations is obtained from basis sets of up to TZ quality and the latter two approaches require additional MP2 calculations with basis sets of up to QZ quality. We also assess the performance of the basis-set extrapolations and additivity schemes for a set of 20 basis-set limit CCSD atomization energies of larger molecules including amino acids, DNA/RNA bases, aromatic compounds, and platonic hydrocarbon cages. We obtain the following RMSDs for the above methods: 10.2 (global extrapolation), 5.7 (system-dependent extrapolation), and 2.9 (additivity scheme) kJ mol{sup –1}.« less

Estimating the CCSD basis-set limit energy from small basis sets: basis-set extrapolations vs additivity schemes

NASA Astrophysics Data System (ADS)

Spackman, Peter R.; Karton, Amir

2015-05-01

Coupled cluster calculations with all single and double excitations (CCSD) converge exceedingly slowly with the size of the one-particle basis set. We assess the performance of a number of approaches for obtaining CCSD correlation energies close to the complete basis-set limit in conjunction with relatively small DZ and TZ basis sets. These include global and system-dependent extrapolations based on the A + B/Lα two-point extrapolation formula, and the well-known additivity approach that uses an MP2-based basis-set-correction term. We show that the basis set convergence rate can change dramatically between different systems(e.g.it is slower for molecules with polar bonds and/or second-row elements). The system-dependent basis-set extrapolation scheme, in which unique basis-set extrapolation exponents for each system are obtained from lower-cost MP2 calculations, significantly accelerates the basis-set convergence relative to the global extrapolations. Nevertheless, we find that the simple MP2-based basis-set additivity scheme outperforms the extrapolation approaches. For example, the following root-mean-squared deviations are obtained for the 140 basis-set limit CCSD atomization energies in the W4-11 database: 9.1 (global extrapolation), 3.7 (system-dependent extrapolation), and 2.4 (additivity scheme) kJ mol-1. The CCSD energy in these approximations is obtained from basis sets of up to TZ quality and the latter two approaches require additional MP2 calculations with basis sets of up to QZ quality. We also assess the performance of the basis-set extrapolations and additivity schemes for a set of 20 basis-set limit CCSD atomization energies of larger molecules including amino acids, DNA/RNA bases, aromatic compounds, and platonic hydrocarbon cages. We obtain the following RMSDs for the above methods: 10.2 (global extrapolation), 5.7 (system-dependent extrapolation), and 2.9 (additivity scheme) kJ mol-1.

Updated Prognostic Model for Predicting Overall Survival in First-Line Chemotherapy for Patients With Metastatic Castration-Resistant Prostate Cancer

PubMed Central

Halabi, Susan; Lin, Chen-Yen; Kelly, W. Kevin; Fizazi, Karim S.; Moul, Judd W.; Kaplan, Ellen B.; Morris, Michael J.; Small, Eric J.

2014-01-01

Purpose Prognostic models for overall survival (OS) for patients with metastatic castration-resistant prostate cancer (mCRPC) are dated and do not reflect significant advances in treatment options available for these patients. This work developed and validated an updated prognostic model to predict OS in patients receiving first-line chemotherapy. Methods Data from a phase III trial of 1,050 patients with mCRPC were used (Cancer and Leukemia Group B CALGB-90401 [Alliance]). The data were randomly split into training and testing sets. A separate phase III trial served as an independent validation set. Adaptive least absolute shrinkage and selection operator selected eight factors prognostic for OS. A predictive score was computed from the regression coefficients and used to classify patients into low- and high-risk groups. The model was assessed for its predictive accuracy using the time-dependent area under the curve (tAUC). Results The model included Eastern Cooperative Oncology Group performance status, disease site, lactate dehydrogenase, opioid analgesic use, albumin, hemoglobin, prostate-specific antigen, and alkaline phosphatase. Median OS values in the high- and low-risk groups, respectively, in the testing set were 17 and 30 months (hazard ratio [HR], 2.2; P < .001); in the validation set they were 14 and 26 months (HR, 2.9; P < .001). The tAUCs were 0.73 (95% CI, 0.70 to 0.73) and 0.76 (95% CI, 0.72 to 0.76) in the testing and validation sets, respectively. Conclusion An updated prognostic model for OS in patients with mCRPC receiving first-line chemotherapy was developed and validated on an external set. This model can be used to predict OS, as well as to better select patients to participate in trials on the basis of their prognosis. PMID:24449231

Dynamic Trial-by-Trial Recoding of Task-Set Representations in the Frontoparietal Cortex Mediates Behavioral Flexibility

PubMed Central

Qiao, Lei; Zhang, Lijie

2017-01-01

Cognitive flexibility forms the core of the extraordinary ability of humans to adapt, but the precise neural mechanisms underlying our ability to nimbly shift between task sets remain poorly understood. Recent functional magnetic resonance imaging (fMRI) studies employing multivoxel pattern analysis (MVPA) have shown that a currently relevant task set can be decoded from activity patterns in the frontoparietal cortex, but whether these regions support the dynamic transformation of task sets from trial to trial is not clear. Here, we combined a cued task-switching protocol with human (both sexes) fMRI, and harnessed representational similarity analysis (RSA) to facilitate a novel assessment of trial-by-trial changes in neural task-set representations. We first used MVPA to define task-sensitive frontoparietal and visual regions and found that neural task-set representations on switch trials are less stably encoded than on repeat trials. We then exploited RSA to show that the neural representational pattern dissimilarity across consecutive trials is greater for switch trials than for repeat trials, and that the degree of this pattern dissimilarity predicts behavior. Moreover, the overall neural pattern of representational dissimilarities followed from the assumption that repeating sets, compared with switching sets, results in stronger neural task representations. Finally, when moving from cue to target phase within a trial, pattern dissimilarities tracked the transformation from previous-trial task representations to the currently relevant set. These results provide neural evidence for the longstanding assumptions of an effortful task-set reconfiguration process hampered by task-set inertia, and they demonstrate that frontoparietal and stimulus processing regions support “dynamic adaptive coding,” flexibly representing changing task sets in a trial-by-trial fashion. SIGNIFICANCE STATEMENT Humans can fluently switch between different tasks, reflecting an ability to dynamically configure “task sets,” rule representations that link stimuli to appropriate responses. Recent studies show that neural signals in frontal and parietal brain regions can tell us which of two tasks a person is currently performing. However, it is not known whether these regions are also involved in dynamically reconfiguring task-set representations when switching between tasks. Here we measured human brain activity during task switching and tracked the similarity of neural task-set representations from trial to trial. We show that frontal and parietal brain regions flexibly recode changing task sets in a trial-by-trial fashion, and that task-set similarity over consecutive trials predicts behavior. PMID:28972126

Dynamic switching between semantic and episodic memory systems.

PubMed

Kompus, Kristiina; Olsson, Carl-Johan; Larsson, Anne; Nyberg, Lars

2009-09-01

It has been suggested that episodic and semantic long-term memory systems interact during retrieval. Here we examined the flexibility of memory retrieval in an associative task taxing memories of different strength, assumed to differentially engage episodic and semantic memory. Healthy volunteers were pre-trained on a set of 36 face-name pairs over a 6-week period. Another set of 36 items was shown only once during the same time period. About 3 months after the training period all items were presented in a randomly intermixed order in an event-related fMRI study of face-name memory. Once presented items differentially activated anterior cingulate cortex and a right prefrontal region that previously have been associated with episodic retrieval mode. High-familiar items were associated with stronger activation of posterior cortices and a left frontal region. These findings fit a model of memory retrieval by which early processes determine, on a trial-by-trial basis, if the task can be solved by the default semantic system. If not, there is a dynamic shift to cognitive control processes that guide retrieval from episodic memory.

Slowness in Movement Initiation is Associated with Proactive Inhibitory Network Dysfunction in Parkinson's Disease.

PubMed

Criaud, Marion; Poisson, Alice; Thobois, Stéphane; Metereau, Elise; Redouté, Jérôme; Ibarrola, Danièle; Baraduc, Pierre; Broussolle, Emmanuel; Strafella, Antonio P; Ballanger, Bénédicte; Boulinguez, Philippe

2016-04-02

Impairment in initiating movements in PD might be related to executive dysfunction associated with abnormal proactive inhibitory control, a pivotal mechanism consisting in gating movement initiation in uncertain contexts. Testing this hypothesis on the basis of direct neural-based evidence. Twelve PD patients on antiparkinsonian medication and fifteen matched healthy controls performed a simple reaction time task during event-related functional MRI scanning. For all subjects, the level of activation of SMA was found to predict RT on a trial-by-trial basis. The increase in movement initiation latency observed in PD patients with regard to controls was associated with pre-stimulus BOLD increases within several nodes of the proactive inhibitory network (caudate nucleus, precuneus, thalamus). These results provide physiological data consistent with impaired control of proactive inhibition over motor initiation in PD. Patients would be locked into a mode of control maintaining anticipated inhibition over willed movements even when the situation does not require action restraint. The functional and neurochemical bases of brain activity associated with executive settings need to be addressed thoroughly in future studies to better understand disabling symptoms that have few therapeutic options like akinesia.

OTC polyethylene glycol 3350 and pharmacists' role in managing constipation.

PubMed

Horn, John R; Mantione, Maria Marzella; Johanson, John F

2012-01-01

To define constipation, assess the pharmacist's role in identifying and treating constipation, and review clinical evidence for the efficacy, safety, and tolerability of polyethylene glycol (PEG) 3350 (MiraLAX-Merck Consumer Care), an osmotic laxative now available over the counter (OTC), across a variety of patient populations routinely encountered in pharmacy settings. Systematic PubMed search of the primary literature for constipation treatment guidelines and clinical trial results for PEG 3350. Pharmacists have a unique role in assisting patients with identifying and managing constipation. Multiple controlled clinical trials have established the efficacy, safety, and tolerability of PEG 3350 at its recommended dose of 17 g once daily. On the basis of this evidence, various professional groups have recommended PEG 3350 for use in improving stool frequency and consistency in patients with constipation. PEG 3350 is approved for short-term use, including treatment of constipation caused by medications. Pharmacists can play an important role in managing constipation with OTC agents. Compared with other available OTC agents, PEG 3350 can be recommended to patients suffering from constipation on the basis of a large body of clinical evidence supporting its efficacy and safety, as well as the high patient acceptance shown for its palatability and once-daily dosing.

Laboratory agonistic interactions demonstrate failure of an introduced crayfish to dominate two imperiled endemic crayfishes

USGS Publications Warehouse

Rahm, E.J.; Griffith, S.A.; Noltie, Douglas B.; DiStefano, R.J.

2005-01-01

Following its introduction into the St. Francis River drainage, Missouri, U.S.A., the woodland crayfish, Orconectes hylas has expanded its range there; simultaneously populations of two imperiled endemic species, the Big Creek crayfish, O. peruncus, and the St. Francis River crayfish, O. quadruncus have declined therein. In seeking a basis for this decline, our study objective was to test whether the outcome of aggressive inter-specific interactions would favor O. hylas. We studied agonistic encounters between size-matched pairs of same-sex individuals of the introduced and the endemic species in a laboratory setting, first with juveniles and then with adults. Within each life stage, we conducted four sets of laboratory experiments, with approximately 20 trials in each set: (1) O. hylas males versus O. peruncus males, (2) O. hylas males versus O. quadruncus males, (3) O. hylas females versus O. peruncus females, and (4) O. hylas females versus O. quadruncus females. In addition, these same four experiment sets were repeated using larger adult O. hylas crayfish matched with smaller-sized adult endemics, mimicking the mismatch in adult sizes that occurs in the wild. Within each experiment, every trial was analysed to quantify the frequency of occurrence of three initiation behaviors and to determine the overall outcome of the trial. Results did not show O. hylas (juveniles or adults) to be behaviorally dominant over either endemic species. Orconectes hylas displayed the majority of one of the initiation behaviors significantly more often than did the endemic species in only two of the twelve experiments. Because direct aggressive interaction was not demonstrated to be the mechanism whereby O. peruncus and O. quadruncus are being replaced by O. hylas, other life history and ecological factors will require investigation. ?? Koninklijke Brill NV, 2005.

Impact of an interprofessional shared decision-making and goal-setting decision aid for patients with diabetes on decisional conflict--study protocol for a randomized controlled trial.

PubMed

Yu, Catherine H; Ivers, Noah M; Stacey, Dawn; Rezmovitz, Jeremy; Telner, Deanna; Thorpe, Kevin; Hall, Susan; Settino, Marc; Kaplan, David M; Coons, Michael; Sodhi, Sumeet; Sale, Joanna; Straus, Sharon E

2015-06-27

Competing health concerns present real obstacles to people living with diabetes and other chronic diseases as well as to their primary care providers. Guideline implementation interventions rarely acknowledge this, leaving both patients and providers feeling overwhelmed by the volume of recommended actions. Interprofessional (IP) shared decision-making (SDM) with the use of decision aids may help to set treatment priorities. We developed an evidence-based SDM intervention for patients with diabetes and other conditions that was framed by the IP-SDM model and followed a user-centered approach. Our objective in the present study is to pilot an IP-SDM and goal-setting toolkit following the Knowledge-to-Action Framework to assess (1) intervention fidelity and the feasibility of conducting a larger trial and (2) impact on decisional conflict, diabetes distress, health-related quality of life and patient assessment of chronic illness care. A two-step, parallel-group, clustered randomized controlled trial (RCT) will be conducted, with the primary goal being to assess intervention fidelity and the feasibility of conducting a larger RCT. The first step is a provider-directed implementation only; the second (after a 6-month delay) involves both provider- and patient-directed implementation. Half of the clusters will be assigned to receive the IP-SDM toolkit, and the other will be assigned to be mailed a diabetes guidelines summary. Individual interviews with patients, their family members and health care providers will be conducted upon trial completion to explore toolkit use. A secondary purpose of this trial is to gather estimates of the toolkit's impact on decisional conflict. Secondary outcomes include diabetes distress, quality of life and chronic illness care, which will be assessed on the basis of patient-completed questionnaires of validated scales at baseline and at 6 and 12 months. Multilevel hierarchical regression models will be used to account for the clustered nature of the data. An individualized approach to patients with multiple chronic conditions using SDM and goal setting is a desirable strategy for achieving guideline-concordant treatment in a patient-centered fashion. Our pilot trial will provide insights regarding strategies for the routine implementation of such interventions in clinical practice, and it will offer an assessment of the impact of this approach. Clinicaltrials.gov Identifier: NCT02379078. Date of Registration: 11 February 2015.

Correlation consistent basis sets for the atoms In–Xe

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

Mahler, Andrew; Wilson, Angela K., E-mail: akwilson@unt.edu

In this work, the correlation consistent family of Gaussian basis sets has been expanded to include all-electron basis sets for In–Xe. The methodology for developing these basis sets is described, and several examples of the performance and utility of the new sets have been provided. Dissociation energies and bond lengths for both homonuclear and heteronuclear diatomics demonstrate the systematic convergence behavior with respect to increasing basis set quality expected by the family of correlation consistent basis sets in describing molecular properties. Comparison with recently developed correlation consistent sets designed for use with the Douglas-Kroll Hamiltonian is provided.

Bile Acids in Neurodegenerative Disorders

PubMed Central

Ackerman, Hayley D.; Gerhard, Glenn S.

2016-01-01

Bile acids, a structurally related group of molecules derived from cholesterol, have a long history as therapeutic agents in medicine, from treatment for primarily ocular diseases in ancient Chinese medicine to modern day use as approved drugs for certain liver diseases. Despite evidence supporting a neuroprotective role in a diverse spectrum of age-related neurodegenerative disorders, including several small pilot clinical trials, little is known about their molecular mechanisms or their physiological roles in the nervous system. We review the data reported for their use as treatments for neurodegenerative diseases and their underlying molecular basis. While data from cellular and animal models and clinical trials support potential efficacy to treat a variety of neurodegenerative disorders, the relevant bile acids, their origin, and the precise molecular mechanism(s) by which they confer neuroprotection are not known delaying translation to the clinical setting. PMID:27920719

Good intentions and received wisdom are not good enough: the need for controlled trials in public health.

PubMed

Macintyre, Sally

2011-07-01

In the 1970s Archie Cochrane noted that many healthcare procedures and forms of organisation lacked evidence of effectiveness and efficiency, and argued for improved methods of evaluation, moving from clinical opinion and observation to randomised controlled trials (RCTs). His arguments gradually became accepted in medicine, but there has been considerable resistance among policymakers and researchers to their application to social and public health interventions. This essay argues that opposition to RCTs in public health is often based on a false distinction between healthcare and community settings, and sometimes on a misunderstanding of the principles of RCTs in health care. It suggests that just as in medicine, good intentions and received wisdom are not a sufficient basis for making public policy and allocating public funds for social or health improvement.

Pre-Operative nutrition In Neck of femur Trial (POINT)--carbohydrate loading in patients with fragility hip fracture: study protocol for a randomised controlled trial.

PubMed

Moppett, Iain K; Greenhaff, Paul L; Ollivere, Ben J; Joachim, Theophillus; Lobo, Dileep N; Rowlands, Martin

2014-12-04

Trauma such as hip fracture initiates a neurohumoral stress response that changes the balance between anabolism and catabolism resulting in muscle breakdown and reduced mobilisation. Various studies have demonstrated a reduction in catabolism with pre-operative carbohydrate loading but only in an elective setting. This is a two-centre, randomised double-blinded trial in the United Kingdom. Sample size will be 30 patients (approximately 15 from each centre). Randomisation will be web based using computer-generated concealed tables. Both participants and investigators will be blinded to group allocation. Participants will be >70 years of age, cognitively intact (Abbreviated Mental Score ≥ 7), able to give informed consent, and admitted directly through the emergency department with fractured neck of femur requiring hemiarthroplasty. Intervention will consist of two carbohydrate drinks (Nutricia pre-Op) given the night before, and the morning of the surgery. The control will receive two placebo drinks of equal volume. All participants will receive standard hospital care at the discretion of the clinical team. The primary outcome is the difference between groups in insulin resistance calculated by a glucose tolerance test administered pre-operatively and 24 hours postoperatively. Secondary endpoints will be changes in muscle carbohydrate metabolism (biopsy), mobility (Cumulative Ambulation Score) and subjective measures of tolerability. This is a small-scale pilot study, investigating the benefits and tolerability of carbohydrate loading in an emergency setting in a frail elderly group with known high morbidity and mortality. Positive findings will provide the basis for a larger scale study. Current Controlled Trials ISRCTN91109766 (7 April 2014); NRES ref: 13/EM/0214Trial Sponsor: University of Nottingham Ref.13036.

The Population Structure and Diversity of Eggplant from Asia and the Mediterranean Basin

PubMed Central

Cericola, Fabio; Portis, Ezio; Toppino, Laura; Barchi, Lorenzo; Acciarri, Nazareno; Ciriaci, Tommaso; Sala, Tea; Rotino, Giuseppe Leonardo; Lanteri, Sergio

2013-01-01

A collection of 238 eggplant breeding lines, heritage varieties and selections within local landraces provenanced from Asia and the Mediterranean Basin was phenotyped with respect to key plant and fruit traits, and genotyped using 24 microsatellite loci distributed uniformly throughout the genome. STRUCTURE analysis based on the genotypic data identified two major sub-groups, which to a large extent mirrored the provenance of the entries. With the goal to identify true-breeding types, 38 of the entries were discarded on the basis of microsatellite-based residual heterozygosity, along with a further nine which were not phenotypically uniform. The remaining 191 entries were scored for a set of 19 fruit and plant traits in a replicated experimental field trial. The phenotypic data were subjected to principal component and hierarchical principal component analyses, allowing three major morphological groups to be identified. All three morphological groups were represented in both the “Occidental” and the “Oriental” germplasm, so the correlation between the phenotypic and the genotypic data sets was quite weak. The relevance of these results for evolutionary studies and the further improvement of eggplant are discussed. The population structure of the core set of germplasm shows that it can be used as a basis for an association mapping approach. PMID:24040032

The population structure and diversity of eggplant from Asia and the Mediterranean Basin.

PubMed

Cericola, Fabio; Portis, Ezio; Toppino, Laura; Barchi, Lorenzo; Acciarri, Nazareno; Ciriaci, Tommaso; Sala, Tea; Rotino, Giuseppe Leonardo; Lanteri, Sergio

2013-01-01

A collection of 238 eggplant breeding lines, heritage varieties and selections within local landraces provenanced from Asia and the Mediterranean Basin was phenotyped with respect to key plant and fruit traits, and genotyped using 24 microsatellite loci distributed uniformly throughout the genome. STRUCTURE analysis based on the genotypic data identified two major sub-groups, which to a large extent mirrored the provenance of the entries. With the goal to identify true-breeding types, 38 of the entries were discarded on the basis of microsatellite-based residual heterozygosity, along with a further nine which were not phenotypically uniform. The remaining 191 entries were scored for a set of 19 fruit and plant traits in a replicated experimental field trial. The phenotypic data were subjected to principal component and hierarchical principal component analyses, allowing three major morphological groups to be identified. All three morphological groups were represented in both the "Occidental" and the "Oriental" germplasm, so the correlation between the phenotypic and the genotypic data sets was quite weak. The relevance of these results for evolutionary studies and the further improvement of eggplant are discussed. The population structure of the core set of germplasm shows that it can be used as a basis for an association mapping approach.

Randomised trials comparing different healthcare settings: an exploratory review of the impact of pre-trial preferences on participation, and discussion of other methodological challenges.

PubMed

Corbett, Mark S; Watson, Judith; Eastwood, Alison

2016-10-19

We recently published a systematic review of different healthcare settings (such as outpatient, community or home) for administering intravenous chemotherapy, and concluded that performing conventionally designed randomised trials was difficult. The main problems were achieving adequate trial accrual rates and recruiting a study population which adequately represented the target population of interest. These issues stemmed from the fact that potential participants may have had pre-trial perceptions about the trial settings they may be allocated; such preferences will sometimes be strong enough for patients to decline an invitation to participate in a trial. A patient preference trial design (in which patients can choose, or be randomised to, an intervention) may have obviated these recruitment issues, although none of the trials used such a design. In order to gain a better understanding of the broader prevalence and extent of these preference issues (and any other methodological challenges), we undertook an exploratory review of settings trials in any area of healthcare treatment research. We searched The Cochrane Library and Google Scholar and used snowballing methods to identify trials comparing different healthcare settings. Trial accrual was affected by patient preferences for a setting in 15 of the 16 identified studies; birth setting trials were the most markedly affected, with between 68 % and 85 % of eligible women declining to participate specifically because of preference for a particular healthcare setting. Recruitment into substance abuse and chemotherapy setting studies was also notably affected by preferences. Only four trials used a preference design: the proportion of eligible patients choosing to participate via a preference group ranged from between 33 % and 67 %. In trials of healthcare settings, accrual may be seriously affected by patient preferences. The use of trial designs which incorporate a preference component should therefore strongly be considered. When designing such trials, investigators should consider settings to be complex interventions, which are likely to have linked components which may be difficult to control for. Careful thought is also needed regarding the choice of comparator settings and the most appropriate outcome measures to be used.

21 CFR 886.1405 - Ophthalmic trial lens set.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ophthalmic trial lens set. 886.1405 Section 886...) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1405 Ophthalmic trial lens set. (a) Identification. An ophthalmic trial lens set is a device that is a set of lenses of various dioptric powers...

Mapping working memory retrieval in space and in time: A combined electroencephalography and electrocorticography approach.

PubMed

Zhang, Qiong; van Vugt, Marieke; Borst, Jelmer P; Anderson, John R

2018-07-01

In this study, we investigated the time course and neural correlates of the retrieval process underlying visual working memory. We made use of a rare dataset in which the same task was recorded using both scalp electroencephalography (EEG) and Electrocorticography (ECoG), respectively. This allowed us to examine with great spatial and temporal detail how the retrieval process works, and in particular how the medial temporal lobe (MTL) is involved. In each trial, participants judged whether a probe face had been among a set of recently studied faces. With a method that combines hidden semi-Markov models and multivariate pattern analysis, the neural signal was decomposed into a sequence of latent cognitive stages with information about their durations on a trial-by-trial basis. Analyzed separately, EEG and ECoG data yielded converging results on discovered stages and their interpretation, which reflected 1) a brief pre-attention stage, 2) encoding the stimulus, 3) retrieving the studied set, and 4) making a decision. Combining these stages with the high spatial resolution of ECoG suggested that activity in the temporal cortex reflected item familiarity in the retrieval stage; and that once retrieval is complete, there is active maintenance of the studied face set in the decision stage in the MTL. During this same period, the frontal cortex guides the decision by means of theta coupling with the MTL. These observations generalize previous findings on the role of MTL theta from long-term memory tasks to short-term memory tasks. Copyright © 2018 Elsevier Inc. All rights reserved.

Push it to the limit: Characterizing the convergence of common sequences of basis sets for intermolecular interactions as described by density functional theory

NASA Astrophysics Data System (ADS)

Witte, Jonathon; Neaton, Jeffrey B.; Head-Gordon, Martin

2016-05-01

With the aim of systematically characterizing the convergence of common families of basis sets such that general recommendations for basis sets can be made, we have tested a wide variety of basis sets against complete-basis binding energies across the S22 set of intermolecular interactions—noncovalent interactions of small and medium-sized molecules consisting of first- and second-row atoms—with three distinct density functional approximations: SPW92, a form of local-density approximation; B3LYP, a global hybrid generalized gradient approximation; and B97M-V, a meta-generalized gradient approximation with nonlocal correlation. We have found that it is remarkably difficult to reach the basis set limit; for the methods and systems examined, the most complete basis is Jensen's pc-4. The Dunning correlation-consistent sequence of basis sets converges slowly relative to the Jensen sequence. The Karlsruhe basis sets are quite cost effective, particularly when a correction for basis set superposition error is applied: counterpoise-corrected def2-SVPD binding energies are better than corresponding energies computed in comparably sized Dunning and Jensen bases, and on par with uncorrected results in basis sets 3-4 times larger. These trends are exhibited regardless of the level of density functional approximation employed. A sense of the magnitude of the intrinsic incompleteness error of each basis set not only provides a foundation for guiding basis set choice in future studies but also facilitates quantitative comparison of existing studies on similar types of systems.

Current developments in the treatment of early-stage classical Hodgkin lymphoma.

PubMed

Borchmann, Sven; von Tresckow, Bastian; Engert, Andreas

2016-09-01

After presenting the current treatment recommendations for early-stage Hodgkin lymphoma, we give an overview on recently published clinical trials in this setting. Furthermore, the potential influence of current trials on the treatment of early-stage Hodgkin lymphoma and integration of newly emerging drugs into treatment protocols will be discussed. Trials attempting treatment de-escalation and omission of radiotherapy on the basis of early interim PET-scans have been disappointing so far, but results of some large trials employing this strategy are still awaited. In contrast, a more defensive strategy of starting treatment with less aggressive doxorubicine, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy and intensifying treatment in early interim PET-positive patients has shown encouraging results. New drugs such as brentuximab vedotin and immune checkpoint inhibitors have shown promising results in relapsed and refractory Hodgkin lymphoma. Clinical trials of brentuximab vedotin in early-stage Hodgkin lymphoma have been initiated. Additionally, biomarker-based treatment de-escalation might be a possible route for future improvements. The challenge for future clinical research in early-stage Hodgkin lymphoma is to continue to cure the majority of patients with first-line treatment while reducing long-term toxicity. New strategies to achieve that goal are currently being developed and will further refine treatment of early-stage Hodgkin lymphoma.

A pilot cluster randomised trial to assess the effect of a structured communication approach on quality of life in secure mental health settings: The Comquol Study.

PubMed

MacInnes, Douglas; Kinane, Catherine; Parrott, Janet; Mansfield, Jacqueline; Craig, Tom; Eldridge, Sandra; Marsh, Ian; Chan, Claire; Hounsome, Natalia; Harrison, George; Priebe, Stefan

2016-09-29

There is a lack of research in forensic settings examining therapeutic relationships. A structured communication approach, placing patients' perspectives at the heart of discussions about their care, was used to improve patients' quality of life in secure settings. The objectives were to: • Establish the feasibility of the trial design • Determine the variability of the outcomes of interest • Estimate the costs of the intervention • If necessary, refine the intervention METHODS: A pilot cluster randomised controlled trial was conducted. Data was collected from July 2012 to January 2015 from participants in 6 medium secure in-patient services in London and Southern England. 55 patients and 47 nurses were in the intervention group with 57 patients and 45 nurses in the control group. The intervention comprised 6 nurse-patient meetings over a 6 month period. Patients rated their satisfaction with a range of domains followed by discussions on improving patient identified problems. Assessments took place at baseline, 6 months, and 12 months. Participants were not blind to their allocated group. The primary outcome was self-reported quality of life collected by a researcher blind to participants' allocation status. The randomisation procedures and intervention approach functioned well. The measures used were understood by the participants and gave relevant outcome information. The response rates were good with low patient withdrawal rates. The quality of life estimated treatment effect was 0.2 (95 % CI: -0.4 to 0.8) at 6 months and 0.4 (95 % CI: -0.3 to 1.1) indicating the likely extreme boundaries of effect in the main trial. The estimated treatment effect of the primary outcome is clinically important, and a positive effect of the intervention is not ruled out. The estimate of the ICC for the primary outcome at 6 and 12 months was 0.04 (0.00 to 0.17) and 0.05 (0.00 to 0.18). The cost of the intervention was £529 per patient. The trial design was viable as the basis for a full-scale trial. A full trial is justified to estimate the effect of the intervention with greater certainty. The variability of the outcomes could be used to calculate numbers needed for a full-scale trial. Ratings of need for therapeutic security may be useful in any future study. Current Controlled Trials ISRCTN34145189 . Retrospectively registered 22 June 2012.

A new adaptive videogame for training attention and executive functions: design principles and initial validation.

PubMed

Montani, Veronica; De Filippo De Grazia, Michele; Zorzi, Marco

2014-01-01

A growing body of evidence suggests that action videogames could enhance a variety of cognitive skills and more specifically attention skills. The aim of this study was to develop a novel adaptive videogame to support the rehabilitation of the most common consequences of traumatic brain injury (TBI), that is the impairment of attention and executive functions. TBI patients can be affected by psychomotor slowness and by difficulties in dealing with distraction, maintain a cognitive set for a long time, processing different simultaneously presented stimuli, and planning purposeful behavior. Accordingly, we designed a videogame that was specifically conceived to activate those functions. Playing involves visuospatial planning and selective attention, active maintenance of the cognitive set representing the goal, and error monitoring. Moreover, different game trials require to alternate between two tasks (i.e., task switching) or to perform the two tasks simultaneously (i.e., divided attention/dual-tasking). The videogame is controlled by a multidimensional adaptive algorithm that calibrates task difficulty on-line based on a model of user performance that is updated on a trial-by-trial basis. We report simulations of user performance designed to test the adaptive game as well as a validation study with healthy participants engaged in a training protocol. The results confirmed the involvement of the cognitive abilities that the game is supposed to enhance and suggested that training improved attentional control during play.

A new adaptive videogame for training attention and executive functions: design principles and initial validation

PubMed Central

Montani, Veronica; De Filippo De Grazia, Michele; Zorzi, Marco

2014-01-01

A growing body of evidence suggests that action videogames could enhance a variety of cognitive skills and more specifically attention skills. The aim of this study was to develop a novel adaptive videogame to support the rehabilitation of the most common consequences of traumatic brain injury (TBI), that is the impairment of attention and executive functions. TBI patients can be affected by psychomotor slowness and by difficulties in dealing with distraction, maintain a cognitive set for a long time, processing different simultaneously presented stimuli, and planning purposeful behavior. Accordingly, we designed a videogame that was specifically conceived to activate those functions. Playing involves visuospatial planning and selective attention, active maintenance of the cognitive set representing the goal, and error monitoring. Moreover, different game trials require to alternate between two tasks (i.e., task switching) or to perform the two tasks simultaneously (i.e., divided attention/dual-tasking). The videogame is controlled by a multidimensional adaptive algorithm that calibrates task difficulty on-line based on a model of user performance that is updated on a trial-by-trial basis. We report simulations of user performance designed to test the adaptive game as well as a validation study with healthy participants engaged in a training protocol. The results confirmed the involvement of the cognitive abilities that the game is supposed to enhance and suggested that training improved attentional control during play. PMID:24860529

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

Witte, Jonathon; Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California 94720; Neaton, Jeffrey B.

With the aim of systematically characterizing the convergence of common families of basis sets such that general recommendations for basis sets can be made, we have tested a wide variety of basis sets against complete-basis binding energies across the S22 set of intermolecular interactions—noncovalent interactions of small and medium-sized molecules consisting of first- and second-row atoms—with three distinct density functional approximations: SPW92, a form of local-density approximation; B3LYP, a global hybrid generalized gradient approximation; and B97M-V, a meta-generalized gradient approximation with nonlocal correlation. We have found that it is remarkably difficult to reach the basis set limit; for the methodsmore » and systems examined, the most complete basis is Jensen’s pc-4. The Dunning correlation-consistent sequence of basis sets converges slowly relative to the Jensen sequence. The Karlsruhe basis sets are quite cost effective, particularly when a correction for basis set superposition error is applied: counterpoise-corrected def2-SVPD binding energies are better than corresponding energies computed in comparably sized Dunning and Jensen bases, and on par with uncorrected results in basis sets 3-4 times larger. These trends are exhibited regardless of the level of density functional approximation employed. A sense of the magnitude of the intrinsic incompleteness error of each basis set not only provides a foundation for guiding basis set choice in future studies but also facilitates quantitative comparison of existing studies on similar types of systems.« less

Marketing depression care management to employers: design of a randomized controlled trial

PubMed Central

2010-01-01

Background Randomized trials demonstrate that depression care management can improve clinical and work outcomes sufficiently for selected employers to realize a return on investment. Employers can now purchase depression products that provide depression care management, defined as employee screening, education, monitoring, and clinician feedback for all depressed employees. We developed an intervention to encourage employers to purchase a depression product that offers the type, intensity, and duration of care management shown to improve clinical and work outcomes. Methods In a randomized controlled trial conducted with 360 employers of 30 regional business coalitions, the research team proposes to compare the impact of a value-based marketing intervention to usual-care marketing on employer purchase of depression products. The study will also identify mediators and organizational-level moderators of intervention impact. Employers randomized to the value-based condition receive a presentation encouraging them to purchase depression products scientifically shown to benefit the employee and the employer. Employers randomized to the usual-care condition receive a presentation encouraging them to monitor and improve quality indicators for outpatient depression treatment. Because previous research demonstrates that the usual-care intervention will have little to no impact on employer purchasing, depression product purchasing rates in the usual-care condition capture vendor efforts to market depression products to employers in both conditions while the value-based intervention is being conducted. Employers in both conditions are also provided free technical assistance to undertake the actions each presentation encourages. The research team will use intent-to-treat models of all available data to evaluate intervention impact on the purchase of depression products using a cumulative incidence analysis of 12- and 24-month data. Discussion By addressing the 'value to whom?' question, the study advances knowledge about one of the most pivotal problems in the translation of evidence-based care to 'real world' settings: whether purchasers can be influenced to buy healthcare products on the basis of value and not exclusively on the basis of cost. If value-based marketing increases depression product purchase rates over usual care, this study will provide encouragement to market new healthcare products on the basis of the product's value to the purchaser as well as the recipient of care. Trial Registration Clinical Trials Registration Number: NCT01013220 PMID:20233448

Accuracy of Lagrange-sinc functions as a basis set for electronic structure calculations of atoms and molecules

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

Choi, Sunghwan; Hong, Kwangwoo; Kim, Jaewook

2015-03-07

We developed a self-consistent field program based on Kohn-Sham density functional theory using Lagrange-sinc functions as a basis set and examined its numerical accuracy for atoms and molecules through comparison with the results of Gaussian basis sets. The result of the Kohn-Sham inversion formula from the Lagrange-sinc basis set manifests that the pseudopotential method is essential for cost-effective calculations. The Lagrange-sinc basis set shows faster convergence of the kinetic and correlation energies of benzene as its size increases than the finite difference method does, though both share the same uniform grid. Using a scaling factor smaller than or equal tomore » 0.226 bohr and pseudopotentials with nonlinear core correction, its accuracy for the atomization energies of the G2-1 set is comparable to all-electron complete basis set limits (mean absolute deviation ≤1 kcal/mol). The same basis set also shows small mean absolute deviations in the ionization energies, electron affinities, and static polarizabilities of atoms in the G2-1 set. In particular, the Lagrange-sinc basis set shows high accuracy with rapid convergence in describing density or orbital changes by an external electric field. Moreover, the Lagrange-sinc basis set can readily improve its accuracy toward a complete basis set limit by simply decreasing the scaling factor regardless of systems.« less

Using routinely recorded data in the UK to assess outcomes in a randomised controlled trial: The Trials of Access.

PubMed

Powell, G A; Bonnett, L J; Tudur-Smith, C; Hughes, D A; Williamson, P R; Marson, A G

2017-08-23

In the UK, routinely recorded data may benefit prospective studies including randomised controlled trials (RCTs). In an on-going study, we aim to assess the feasibility of access and agreement of routinely recorded clinical and non-clinical data compared to data collected during a RCT using standard prospective methods. This paper will summarise available UK routinely recorded data sources and discuss our experience with the feasibility of accessing routinely recorded data for participants of a RCT before finally proposing recommendations for improving the access and implementation of routinely recorded data in RCTs. Setting: the case study RCT is the Standard and New Antiepileptic Drugs II (SANAD II) trial, a pragmatic, UK, multicentre, phase IV RCT assessing the clinical and cost-effectiveness of antiepileptic drug treatments for newly diagnosed epilepsy. 98 participants have provided written consent to permit the request of routinely recorded data. Study procedures: routinely recorded clinical and non-clinical data were identified and data requested through formal applications from available data holders for the duration that participants have been recruited into SANAD II. The feasibility of accessing routinely recorded data during a RCT is assessed and recommendations for improving access proposed. Secondary-care clinical and socioeconomic data is recorded on a national basis and can be accessed, although there are limitations in the application process. Primary-care data are recorded by a number of organisations on a de-identified basis but access for specific individuals has not been feasible. Access to data recorded by non-clinical sources, including The Department for Work and Pensions and The Driving and Vehicle Licensing Agency, was not successful. Recommendations discussed include further research to assess the attributes of routinely recorded data, an assessment of public perceptions and the development of strategies to collaboratively improve access to routinely recorded data for research. International Standard Randomised Controlled Trials, ISRCTN30294119 . Registered on 3 July 2012. EudraCT No: 2012-001884-64. Registered on 9 May 2012.

The treatment of medial tibial stress syndrome in athletes; a randomized clinical trial

PubMed Central

2012-01-01

Background The only three randomized trials on the treatment of MTSS were all performed in military populations. The treatment options investigated in this study were not previously examined in athletes. This study investigated if functional outcome of three common treatment options for medial tibial stress syndrome (MTSS) in athletes in a non-military setting was the same. Methods The study design was randomized and multi-centered. Physical therapists and sports physicians referred athletes with MTSS to the hospital for inclusion. 81 athletes were assessed for eligibility of which 74 athletes were included and randomized to three treatment groups. Group one performed a graded running program, group two performed a graded running program with additional stretching and strengthening exercises for the calves, while group three performed a graded running program with an additional sports compression stocking. The primary outcome measure was: time to complete a running program (able to run 18 minutes with high intensity) and secondary outcome was: general satisfaction with treatment. Results 74 Athletes were randomized and included of which 14 did not complete the study due a lack of progress (18.9%). The data was analyzed on an intention-to-treat basis. Time to complete a running program and general satisfaction with the treatment were not significantly different between the three treatment groups. Conclusion This was the first randomized trial on the treatment of MTSS in athletes in a non-military setting. No differences were found between the groups for the time to complete a running program. Trial registration CCMO; NL23471.098.08 PMID:22464032

Optimization of selected molecular orbitals in group basis sets.

PubMed

Ferenczy, György G; Adams, William H

2009-04-07

We derive a local basis equation which may be used to determine the orbitals of a group of electrons in a system when the orbitals of that group are represented by a group basis set, i.e., not the basis set one would normally use but a subset suited to a specific electronic group. The group orbitals determined by the local basis equation minimize the energy of a system when a group basis set is used and the orbitals of other groups are frozen. In contrast, under the constraint of a group basis set, the group orbitals satisfying the Huzinaga equation do not minimize the energy. In a test of the local basis equation on HCl, the group basis set included only 12 of the 21 functions in a basis set one might ordinarily use, but the calculated active orbital energies were within 0.001 hartree of the values obtained by solving the Hartree-Fock-Roothaan (HFR) equation using all 21 basis functions. The total energy found was just 0.003 hartree higher than the HFR value. The errors with the group basis set approximation to the Huzinaga equation were larger by over two orders of magnitude. Similar results were obtained for PCl(3) with the group basis approximation. Retaining more basis functions allows an even higher accuracy as shown by the perfect reproduction of the HFR energy of HCl with 16 out of 21 basis functions in the valence basis set. When the core basis set was also truncated then no additional error was introduced in the calculations performed for HCl with various basis sets. The same calculations with fixed core orbitals taken from isolated heavy atoms added a small error of about 10(-4) hartree. This offers a practical way to calculate wave functions with predetermined fixed core and reduced base valence orbitals at reduced computational costs. The local basis equation can also be used to combine the above approximations with the assignment of local basis sets to groups of localized valence molecular orbitals and to derive a priori localized orbitals. An appropriately chosen localization and basis set assignment allowed a reproduction of the energy of n-hexane with an error of 10(-5) hartree, while the energy difference between its two conformers was reproduced with a similar accuracy for several combinations of localizations and basis set assignments. These calculations include localized orbitals extending to 4-5 heavy atoms and thus they require to solve reduced dimension secular equations. The dimensions are not expected to increase with increasing system size and thus the local basis equation may find use in linear scaling electronic structure calculations.

Accurate Methods for Large Molecular Systems (Preprint)

DTIC Science & Technology

2009-01-06

tensor, EFP calculations are basis set dependent. The smallest recommended basis set is 6- 31++G( d , p )52 The dependence of the computational cost of...and second order perturbation theory (MP2) levels with the 6-31G( d , p ) basis set. Additional SFM tests are presented for a small set of alpha...helices using the 6-31++G( d , p ) basis set. The larger 6-311++G(3df,2p) basis set is employed for creating all EFPs used for non- bonded interactions, since

The Role of Phytochemicals in the Inflammatory Phase of Wound Healing.

PubMed

Shah, Ahmed; Amini-Nik, Saeid

2017-05-16

Historically, plant-based products have been the basis of medicine since before the advent of modern Western medicine. Wound dressings made of honey, curcumin and other phytochemical-rich compounds have been traditionally used. Recently, the mechanisms behind many of these traditional therapies have come to light. In this review, we show that in the context of wound healing, there is a global theme of anti-inflammatory and antioxidant phytochemicals in traditional medicine. Although promising, we discuss the limitations of using some of these phytochemicals in order to warrant more research, ideally in randomized clinical trial settings.

The Role of Phytochemicals in the Inflammatory Phase of Wound Healing

PubMed Central

Shah, Ahmed; Amini-Nik, Saeid

2017-01-01

Historically, plant-based products have been the basis of medicine since before the advent of modern Western medicine. Wound dressings made of honey, curcumin and other phytochemical-rich compounds have been traditionally used. Recently, the mechanisms behind many of these traditional therapies have come to light. In this review, we show that in the context of wound healing, there is a global theme of anti-inflammatory and antioxidant phytochemicals in traditional medicine. Although promising, we discuss the limitations of using some of these phytochemicals in order to warrant more research, ideally in randomized clinical trial settings. PMID:28509885

Approaching the theoretical limit in periodic local MP2 calculations with atomic-orbital basis sets: the case of LiH.

PubMed

Usvyat, Denis; Civalleri, Bartolomeo; Maschio, Lorenzo; Dovesi, Roberto; Pisani, Cesare; Schütz, Martin

2011-06-07

The atomic orbital basis set limit is approached in periodic correlated calculations for solid LiH. The valence correlation energy is evaluated at the level of the local periodic second order Møller-Plesset perturbation theory (MP2), using basis sets of progressively increasing size, and also employing "bond"-centered basis functions in addition to the standard atom-centered ones. Extended basis sets, which contain linear dependencies, are processed only at the MP2 stage via a dual basis set scheme. The local approximation (domain) error has been consistently eliminated by expanding the orbital excitation domains. As a final result, it is demonstrated that the complete basis set limit can be reached for both HF and local MP2 periodic calculations, and a general scheme is outlined for the definition of high-quality atomic-orbital basis sets for solids. © 2011 American Institute of Physics

An expanded calibration study of the explicitly correlated CCSD(T)-F12b method using large basis set standard CCSD(T) atomization energies.

PubMed

Feller, David; Peterson, Kirk A

2013-08-28

The effectiveness of the recently developed, explicitly correlated coupled cluster method CCSD(T)-F12b is examined in terms of its ability to reproduce atomization energies derived from complete basis set extrapolations of standard CCSD(T). Most of the standard method findings were obtained with aug-cc-pV7Z or aug-cc-pV8Z basis sets. For a few homonuclear diatomic molecules it was possible to push the basis set to the aug-cc-pV9Z level. F12b calculations were performed with the cc-pVnZ-F12 (n = D, T, Q) basis set sequence and were also extrapolated to the basis set limit using a Schwenke-style, parameterized formula. A systematic bias was observed in the F12b method with the (VTZ-F12/VQZ-F12) basis set combination. This bias resulted in the underestimation of reference values associated with small molecules (valence correlation energies <0.5 E(h)) and an even larger overestimation of atomization energies for bigger systems. Consequently, caution should be exercised in the use of F12b for high accuracy studies. Root mean square and mean absolute deviation error metrics for this basis set combination were comparable to complete basis set values obtained with standard CCSD(T) and the aug-cc-pVDZ through aug-cc-pVQZ basis set sequence. However, the mean signed deviation was an order of magnitude larger. Problems partially due to basis set superposition error were identified with second row compounds which resulted in a weak performance for the smaller VDZ-F12/VTZ-F12 combination of basis sets.

Rapid testing for malaria in settings where microscopy is available and peripheral clinics where only presumptive treatment is available: a randomised controlled trial in Ghana.

PubMed

Ansah, Evelyn K; Narh-Bana, Solomon; Epokor, Michael; Akanpigbiam, Samson; Quartey, Alberta Amu; Gyapong, John; Whitty, Christopher J M

2010-03-05

To test in West Africa the impact of rapid diagnostic tests on the prescription of antimalarials and antibiotics both where microscopy is used for the diagnosis of malaria and in clinical (peripheral) settings that rely on clinical diagnosis. Randomised, controlled, open label clinical trial. Four clinics in the rural Dangme West district of southern Ghana, one in which microscopy is used for diagnosis of malaria ("microscopy setting") and three where microscopy is not available and diagnosis of malaria is made on the basis of clinical symptoms ("clinical setting"). Patients with suspected malaria. Interventions Patients were randomly assigned to either a rapid diagnostic test or the current diagnostic method at the clinic (microscopy or clinical diagnosis). A blood sample for a research microscopy slide was taken for all patients. The primary outcome was the prescription of antimalarials to patients of any age whose double read research slide was negative for malaria. The major secondary outcomes were the correct prescription of antimalarials, the impact of test results on antibiotic prescription, and the correct prescription of antimalarials in children under 5 years. Of the 9236 patients screened, 3452 were randomised in the clinical setting and 3811 in the microscopy setting. Follow-up to 28 days was 97.6% (7088/7263). In the microscopy setting, 722 (51.6%) of the 1400 patients with negative research slides in the rapid diagnostic test arm were treated for malaria compared with 764 (55.0%) of the 1389 patients in the microscopy arm (adjusted odds ratio 0.87, 95% CI 0.71 to 1.1; P=0.16). In the clinical setting, 578 (53.9%) of the 1072 patients in the rapid diagnostic test arm with negative research slides were treated for malaria compared with 982 (90.1%) of the 1090 patients with negative slides in the clinical diagnosis arm (odds ratio 0.12, 95% CI 0.04 to 0.38; P=0.001). The use of rapid diagnostic tests led to better targeting of antimalarials and antibiotics in the clinical but not the microscopy setting, in both children and adults. There were no deaths in children under 5 years at 28 days follow-up in either arm. Where microscopy already exists, introducing rapid diagnostic tests had limited impact on prescriber behaviour. In settings where microscopy was not available, however, using rapid diagnostic tests led to a significant reduction in the overprescription of antimalarials, without any evidence of clinical harm, and to better targeting of antibiotics. Trial registration ClinicalTrials.gov NCT00493922.

Research gaps identified during systematic reviews of clinical trials: glass-ionomer cements.

PubMed

Mickenautsch, Steffen

2012-06-29

To report the results of an audit concerning research gaps in clinical trials that were accepted for appraisal in authored and published systematic reviews regarding the application of glass-ionomer cements (GIC) in dental practice Information concerning research gaps in trial precision was extracted, following a framework that included classification of the research gap reasons: 'imprecision of information (results)', 'biased information', 'inconsistency or unknown consistency' and 'not the right information', as well as research gap characterization using PICOS elements: population (P), intervention (I), comparison (C), outcomes (O) and setting (S). Internal trial validity assessment was based on the understanding that successful control for systematic error cannot be assured on the basis of inclusion of adequate methods alone, but also requires empirical evidence about whether such attempt was successful. A comprehensive and interconnected coverage of GIC-related clinical topics was established. The most common reasons found for gaps in trial precision were lack of sufficient trials and lack of sufficient large sample size. Only a few research gaps were ascribed to 'Lack of information' caused by focus on mainly surrogate trial outcomes. According to the chosen assessment criteria, a lack of adequate randomisation, allocation concealment and blinding/masking in trials covering all reviewed GIC topics was noted (selection- and detection/performance bias risk). Trial results appear to be less affected by loss-to-follow-up (attrition bias risk). This audit represents an adjunct of the systematic review articles it has covered. Its results do not change the systematic review's conclusions but highlight existing research gaps concerning the precision and internal validity of reviewed trials in detail. These gaps should be addressed in future GIC-related clinical research.

`Voyager': an educational card game

NASA Astrophysics Data System (ADS)

Smith, David Ryan

2003-01-01

`Voyager' is an educational card game involving scientific satellites, developed for use in schools with children aged 9 to 13 years. The idea of the game is to improve pupils' knowledge about the large number of scientific satellites there are in space in a fun way, while also practising numeracy skills. Several copies of the game were produced using funding obtained from the Particle Physics and Astronomy Research Council (PPARC) as a Public Understanding of Science (PUS) award. These initial `trial' versions of the game were taken to three different schools where feedback obtained from both pupils and staff was used to produce a final copy of the game that can be distributed to other schools along with a set of companion notes to form the basis of a science lesson. This article reports the findings of the school trials and indicates possible future developments of other scientific card games that could be beneficial to the classroom.

Prediction of human errors by maladaptive changes in event-related brain networks.

PubMed

Eichele, Tom; Debener, Stefan; Calhoun, Vince D; Specht, Karsten; Engel, Andreas K; Hugdahl, Kenneth; von Cramon, D Yves; Ullsperger, Markus

2008-04-22

Humans engaged in monotonous tasks are susceptible to occasional errors that may lead to serious consequences, but little is known about brain activity patterns preceding errors. Using functional MRI and applying independent component analysis followed by deconvolution of hemodynamic responses, we studied error preceding brain activity on a trial-by-trial basis. We found a set of brain regions in which the temporal evolution of activation predicted performance errors. These maladaptive brain activity changes started to evolve approximately 30 sec before the error. In particular, a coincident decrease of deactivation in default mode regions of the brain, together with a decline of activation in regions associated with maintaining task effort, raised the probability of future errors. Our findings provide insights into the brain network dynamics preceding human performance errors and suggest that monitoring of the identified precursor states may help in avoiding human errors in critical real-world situations.

Prediction of human errors by maladaptive changes in event-related brain networks

PubMed Central

Eichele, Tom; Debener, Stefan; Calhoun, Vince D.; Specht, Karsten; Engel, Andreas K.; Hugdahl, Kenneth; von Cramon, D. Yves; Ullsperger, Markus

2008-01-01

Humans engaged in monotonous tasks are susceptible to occasional errors that may lead to serious consequences, but little is known about brain activity patterns preceding errors. Using functional MRI and applying independent component analysis followed by deconvolution of hemodynamic responses, we studied error preceding brain activity on a trial-by-trial basis. We found a set of brain regions in which the temporal evolution of activation predicted performance errors. These maladaptive brain activity changes started to evolve ≈30 sec before the error. In particular, a coincident decrease of deactivation in default mode regions of the brain, together with a decline of activation in regions associated with maintaining task effort, raised the probability of future errors. Our findings provide insights into the brain network dynamics preceding human performance errors and suggest that monitoring of the identified precursor states may help in avoiding human errors in critical real-world situations. PMID:18427123

Brigatinib for the treatment of ALK-positive advanced non-small cell lung cancer patients.

PubMed

Passaro, A; Prelaj, A; Pochesci, A; Spitaleri, G; Rossi, G; Del Signore, E; Catania, C; de Marinis, F

2017-08-01

Brigatinib (AP-26113, Alunbrig) is a second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) that is highly active in non-small cell lung cancer (NSCLC) harboring ALK translocation. Brigatinib was found to be very active against different ALK resistance mutations that mediate acquired resistance biology processes, particularly G1269A ALK C1156Y, I1171S/T, V1180L and others. Different clinical trials evaluated the activity of brigatinib in crizotinib-resistant patients, confirming high activity with durable response not only in parenchymal disease, but also in intracranial disease. Nowadays, brigatinib is under evaluation in different clinical trials exploring TKI-naive patients in the first-line setting. On the basis of its significant activity results, brigatinib received approval by the FDA for the treatment of patients with ALK-positive metastatic NSCLC who have progressed on or are intolerant to crizotinib. Copyright 2017 Clarivate Analytics.

Optimized auxiliary basis sets for density fitted post-Hartree-Fock calculations of lanthanide containing molecules

NASA Astrophysics Data System (ADS)

Chmela, Jiří; Harding, Michael E.

2018-06-01

Optimised auxiliary basis sets for lanthanide atoms (Ce to Lu) for four basis sets of the Karlsruhe error-balanced segmented contracted def2 - series (SVP, TZVP, TZVPP and QZVPP) are reported. These auxiliary basis sets enable the use of the resolution-of-the-identity (RI) approximation in post Hartree-Fock methods - as for example, second-order perturbation theory (MP2) and coupled cluster (CC) theory. The auxiliary basis sets are tested on an enlarged set of about a hundred molecules where the test criterion is the size of the RI error in MP2 calculations. Our tests also show that the same auxiliary basis sets can be used together with different effective core potentials. With these auxiliary basis set calculations of MP2 and CC quality can now be performed efficiently on medium-sized molecules containing lanthanides.

Women's reasons for participation in a clinical trial for menstrual pain: a qualitative study

PubMed Central

Blödt, Susanne; Witt, Claudia M; Holmberg, Christine

2016-01-01

Objectives The aim of the study was to explore women's motivations for participating in a clinical trial and to evaluate how financial compensation impacts women's explanations for participation. Design, setting and participants Semistructured interviews were conducted face to face or by telephone with 25 of 220 women who participated in a pragmatic randomised trial for app-administered self-care acupressure for dysmenorrhoea (AKUD). Of these 25 women, 10 had entered AKUD knowing they would receive a financial compensation of €30. A purposive sampling strategy was used. Results Women had a long history of seeking help and were unsatisfied with the options available, namely painkillers and oral contraceptives. While interviewees were open to painkillers, they were uneasy about taking them on a monthly basis. The AKUD trial offered the possibility to find an alternative solution. A second reason for participation was the desire to add a new treatment to routine medical care, for which the interviewees considered randomised trials a prerequisite. The financial incentive was a subsidiary motivation in the interviewees' narratives. Conclusions Our results contribute to the ongoing discussion of the impact of financial compensation on research participants' assessment of risk. The interviewed women considered all research participants able to make their own choices regarding trial participation, even in the face of financial compensation or payment of study participants. Furthermore, the importance of clinical trials providing new treatments that could change medical practice might be an overlooked reason for trial participation and could be used in future recruitment strategies. PMID:27965251

Accelerated partial breast irradiation: Past, present, and future

PubMed Central

Tann, Anne W; Hatch, Sandra S; Joyner, Melissa M; Wiederhold, Lee R; Swanson, Todd A

2016-01-01

Accelerated partial breast irradiation (APBI) focuses higher doses of radiation during a shorter interval to the lumpectomy cavity, in the setting of breast conserving therapy for early stage breast cancer. The utilization of APBI has increased in the past decade because of the shorter treatment schedule and a growing body of outcome data showing positive cosmetic outcomes and high local control rates in selected patients undergoing breast conserving therapy. Technological advances in various APBI modalities, including intracavitary and interstitial brachytherapy, intraoperative radiation therapy, and external beam radiation therapy, have made APBI more accessible in the community. Results of early APBI trials served as the basis for the current consensus guidelines, and multiple prospective randomized clinical trials are currently ongoing. The pending long term results of these trials will help us identify optimal candidates that can benefit from ABPI. Here we provide an overview of the clinical and cosmetic outcomes of various APBI techniques and review the current guidelines for selecting suitable breast cancer patients. We also discuss the impact of APBI on the economics of cancer care and patient reported quality of life. PMID:27777879

Ab Initio Density Fitting: Accuracy Assessment of Auxiliary Basis Sets from Cholesky Decompositions.

PubMed

Boström, Jonas; Aquilante, Francesco; Pedersen, Thomas Bondo; Lindh, Roland

2009-06-09

The accuracy of auxiliary basis sets derived by Cholesky decompositions of the electron repulsion integrals is assessed in a series of benchmarks on total ground state energies and dipole moments of a large test set of molecules. The test set includes molecules composed of atoms from the first three rows of the periodic table as well as transition metals. The accuracy of the auxiliary basis sets are tested for the 6-31G**, correlation consistent, and atomic natural orbital basis sets at the Hartree-Fock, density functional theory, and second-order Møller-Plesset levels of theory. By decreasing the decomposition threshold, a hierarchy of auxiliary basis sets is obtained with accuracies ranging from that of standard auxiliary basis sets to that of conventional integral treatments.

Is performance in task-cuing experiments mediated by task set selection or associative compound retrieval?

PubMed

Forrest, Charlotte L D; Monsell, Stephen; McLaren, Ian P L

2014-07-01

Task-cuing experiments are usually intended to explore control of task set. But when small stimulus sets are used, they plausibly afford learning of the response associated with a combination of cue and stimulus, without reference to tasks. In 3 experiments we presented the typical trials of a task-cuing experiment: a cue (colored shape) followed, after a short or long interval, by a digit to which 1 of 2 responses was required. In a tasks condition, participants were (as usual) directed to interpret the cue as an instruction to perform either an odd/even or a high/low classification task. In a cue + stimulus → response (CSR) condition, to induce learning of mappings between cue-stimulus compound and response, participants were, in Experiment 1, given standard task instructions and additionally encouraged to learn the CSR mappings; in Experiment 2, informed of all the CSR mappings and asked to learn them, without standard task instructions; in Experiment 3, required to learn the mappings by trial and error. The effects of a task switch, response congruence, preparation, and transfer to a new set of stimuli differed substantially between the conditions in ways indicative of classification according to task rules in the tasks condition, and retrieval of responses specific to stimulus-cue combinations in the CSR conditions. Qualitative features of the latter could be captured by an associative learning network. Hence associatively based compound retrieval can serve as the basis for performance with a small stimulus set. But when organization by tasks is apparent, control via task set selection is the natural and efficient strategy. PsycINFO Database Record (c) 2014 APA, all rights reserved.

QTL mapping of selenium content using a RIL population in wheat

PubMed Central

Wang, Pei; Wang, Huinan; Liu, Qing; Tian, Xia; Shi, Yanxi

2017-01-01

Selenium (Se) is an essential trace element that plays various roles in human health. Understanding the genetic control of Se content and quantitative trait loci (QTL) mapping provide a basis for Se biofortification of wheat to enhance grain Se content. In the present study, a set of recombinant inbred lines (RILs) derived from two Chinese winter wheat varieties (Tainong18 and Linmai6) was used to detect QTLs for Se content in hydroponic and field trials. In total, 16 QTLs for six Se content-related traits were detected on eight chromosomes, 1B, 2B, 4B, 5A, 5B, 5D, 6A, and 7D. Of these, seven QTLs were detected at the seedling stage and nine at the adult stage. The contribution of each QTL to Se content ranged from 7.37% to 20.22%. QSsece-7D.2, located between marker loci D-3033829 and D-1668160, had the highest contribution (20.22%). This study helps in understanding the genetic basis for Se contents and will provide a basis for gene mapping of Se content in wheat. PMID:28880898

Novel analytical approach for strongly coupled waveguide arrays

NASA Astrophysics Data System (ADS)

Kohli, Niharika; Srivastava, Sangeeta; Sharma, Enakshi K.

2018-02-01

Coupled Mode theory and Variational methods are the most extensively used analytical methods for the study of coupled optical waveguides. In this paper we have discussed a variation of the Ritz Galerkin Variational method (RGVM) wherein the trial field is a superposition of an orthogonal basis set which in turn is generated from superposition of the individual waveguide modal fields using Gram Schmidt Orthogonalization Procedure (GSOP). The conventional coupled mode theory (CCMT), a modified coupled mode theory (MCMT) incorporating interaction terms that are neglected in CCMT, and an RGVM using orthogonal basis set (RG-GSOP) are compared for waveguide arrays of different materials. The exact effective indices values for these planar waveguide arrays are also studied. The different materials have their index-contrasts ranging between the GaAs/ AlGaAs system to Si/SiO2 system. It has been shown that the error in the effective indices values obtained from MCMT and CCMT is higher than RGVM-GSOP especially in the case of higher index-contrast. Therefore, for accurate calculations of the modal characteristics of planar waveguide arrays, even at higher index-contrasts, RGVM-GSOP is the best choice. Moreover, we obtain obviously orthogonal supermode fields and Hermitian matrix from RGVM-GSOP.

Co-enrolment of Participants into Multiple Cancer Trials: Benefits and Challenges.

PubMed

Cafferty, F H; Coyle, C; Rowley, S; Berkman, L; MacKensie, M; Langley, R E

2017-07-01

Opportunities to enter patients into more than one clinical trial are not routinely considered in cancer research and experiences with co-enrolment are rarely reported. Potential benefits of allowing appropriate co-enrolment have been identified in other settings but there is a lack of evidence base or guidance to inform these decisions in oncology. Here, we discuss the benefits and challenges associated with co-enrolment based on experiences in the Add-Aspirin trial - a large, multicentre trial recruiting across a number of tumour types, where opportunities to co-enrol patients have been proactively explored and managed. The potential benefits of co-enrolment include: improving recruitment feasibility; increased opportunities for patients to participate in trials; and collection of robust data on combinations of interventions, which will ensure the ongoing relevance of individual trials and provide more cohesive evidence to guide the management of future patients. There are a number of perceived barriers to co-enrolment in terms of scientific, safety and ethical issues, which warrant consideration on a trial-by-trial basis. In many cases, any potential effect on the results of the trials will be negligible - limited by a number of factors, including the overlap in trial cohorts. Participant representatives stress the importance of autonomy to decide about trial enrolment, providing a compelling argument for offering co-enrolment where there are multiple trials that are relevant to a patient and no concerns regarding safety or the integrity of the trials. A number of measures are proposed for managing and monitoring co-enrolment. Ensuring acceptability to (potential) participants is paramount. Opportunities to enter patients into more than one cancer trial should be considered more routinely. Where planned and managed appropriately, co-enrolment can offer a number of benefits in terms of both scientific value and efficiency of study conduct, and will increase the opportunities for patients to participate in, and benefit from, clinical research. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Reverse engineering of machine-tool settings with modified roll for spiral bevel pinions

NASA Astrophysics Data System (ADS)

Liu, Guanglei; Chang, Kai; Liu, Zeliang

2013-05-01

Although a great deal of research has been dedicated to the synthesis of spiral bevel gears, little related to reverse engineering can be found. An approach is proposed to reverse the machine-tool settings of the pinion of a spiral bevel gear drive on the basis of the blank and tooth surface data obtained by a coordinate measuring machine(CMM). Real tooth contact analysis(RTCA) is performed to preliminary ascertain the contact pattern, the motion curve, as well as the position of the mean contact point. And then the tangent to the contact path and the motion curve are interpolated in the sense of the least square method to extract the initial values of the bias angle and the higher order coefficients(HOC) in modified roll motion. A trial tooth surface is generated by machine-tool settings derived from the local synthesis relating to the initial meshing performances and modified roll motion. An optimization objective is formed which equals the tooth surface deviation between the real tooth surface and the trial tooth surface. The design variables are the parameters describing the meshing performances at the mean contact point in addition to the HOC. When the objective is optimized within an arbitrarily given convergence tolerance, the machine-tool settings together with the HOC are obtained. The proposed approach is verified by a spiral bevel pinion used in the accessory gear box of an aviation engine. The trial tooth surfaces approach to the real tooth surface on the whole in the example. The results show that the convergent tooth surface deviation for the concave side on the average is less than 0.5 μm, and is less than 1.3 μm for the convex side. The biggest tooth surface deviation is 6.7 μm which is located at the corner of the grid on the convex side. Those nodes with relative bigger tooth surface deviations are all located at the boundary of the grid. An approach is proposed to figure out the machine-tool settings of a spiral bevel pinion by way of reverse engineering without having known the theoretical tooth surfaces and the corresponding machine-tool settings.

Relationships between genotype x environment interactions and rank orders for a set of genotypes tested in different environments.

PubMed

Hühn, M; Lotito, S; Piepho, H P

1993-09-01

Multilocation trials in plant breeding lead to cross-classified data sets with rows=genotypes and columns=environments, where the breeder is particularly interested in the rank orders of the genotypes in the different environments. Non-identical rank orders are the result of genotype x environment interactions. Not every interaction, however, causes rank changes among the genotypes (rank-interaction). From a breeder's point of view, interaction is tolerable only as long as it does not affect the rank orders. Therefore, the question arises of under which circumstances does interaction become rank-interaction. This paper contributes to our understanding of this topic. In our study we emphasized the detection of relationships between the similarity of the rank orders (measured by Kendall's coefficient of concordance W) and the functions of the diverse variance components (genotypes, environments, interaction, error). On the basis of extensive data sets on different agricultural crops (faba bean, fodder beet, sugar beet, oats, winter rape) obtained from registration trials (1985-1989) carried out in the Federal Republic of Germany, we obtained the following as main result: W ≅ σ 2 (g) /(σ 2 (g) + σ 2 (v) ) where σ 2 (g) =genotypic variance and σ 2 (v) = σ 2 (ge) + σ 2 (o) /L with σ 2 (ge) =interaction variance, σ 2 (o) =error variance and L=number of replications.

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

Rossi, Tuomas P., E-mail: tuomas.rossi@alumni.aalto.fi; Sakko, Arto; Puska, Martti J.

We present an approach for generating local numerical basis sets of improving accuracy for first-principles nanoplasmonics simulations within time-dependent density functional theory. The method is demonstrated for copper, silver, and gold nanoparticles that are of experimental interest but computationally demanding due to the semi-core d-electrons that affect their plasmonic response. The basis sets are constructed by augmenting numerical atomic orbital basis sets by truncated Gaussian-type orbitals generated by the completeness-optimization scheme, which is applied to the photoabsorption spectra of homoatomic metal atom dimers. We obtain basis sets of improving accuracy up to the complete basis set limit and demonstrate thatmore » the performance of the basis sets transfers to simulations of larger nanoparticles and nanoalloys as well as to calculations with various exchange-correlation functionals. This work promotes the use of the local basis set approach of controllable accuracy in first-principles nanoplasmonics simulations and beyond.« less

Updating the OMERACT filter: core areas as a basis for defining core outcome sets.

PubMed

Kirwan, John R; Boers, Maarten; Hewlett, Sarah; Beaton, Dorcas; Bingham, Clifton O; Choy, Ernest; Conaghan, Philip G; D'Agostino, Maria-Antonietta; Dougados, Maxime; Furst, Daniel E; Guillemin, Francis; Gossec, Laure; van der Heijde, Désirée M; Kloppenburg, Margreet; Kvien, Tore K; Landewé, Robert B M; Mackie, Sarah L; Matteson, Eric L; Mease, Philip J; Merkel, Peter A; Ostergaard, Mikkel; Saketkoo, Lesley Ann; Simon, Lee; Singh, Jasvinder A; Strand, Vibeke; Tugwell, Peter

2014-05-01

The Outcome Measures in Rheumatology (OMERACT) Filter provides guidelines for the development and validation of outcome measures for use in clinical research. The "Truth" section of the OMERACT Filter presupposes an explicit framework for identifying the relevant core outcomes that are universal to all studies of the effects of intervention effects. There is no published outline for instrument choice or development that is aimed at measuring outcome, was derived from broad consensus over its underlying philosophy, or includes a structured and documented critique. Therefore, a new proposal for defining core areas of measurement ("Filter 2.0 Core Areas of Measurement") was presented at OMERACT 11 to explore areas of consensus and to consider whether already endorsed core outcome sets fit into this newly proposed framework. Discussion groups critically reviewed the extent to which case studies of current OMERACT Working Groups complied with or negated the proposed framework, whether these observations had a more general application, and what issues remained to be resolved. Although there was broad acceptance of the framework in general, several important areas of construction, presentation, and clarity of the framework were questioned. The discussion groups and subsequent feedback highlighted 20 such issues. These issues will require resolution to reach consensus on accepting the proposed Filter 2.0 framework of Core Areas as the basis for the selection of Core Outcome Domains and hence appropriate Core Outcome Sets for clinical trials.

A methodological approach for assessing the uptake of core outcome sets using ClinicalTrials.gov: findings from a review of randomised controlled trials of rheumatoid arthritis.

PubMed

Kirkham, Jamie J; Clarke, Mike; Williamson, Paula R

2017-05-17

Objective  To assess the uptake of the rheumatoid arthritis core outcome set using a new assessment method of calculating uptake from data in clinical trial registry entries. Design  Review of randomised trials. Setting  ClinicalTrials.gov. Subjects  273 randomised trials of drug interventions for the treatment of rheumatoid arthritis and registered in ClinicalTrials.gov between 2002 and 2016. Full publications were identified for completed studies from information in the trial registry or from an internet search using Google and the citation database Web of Science. Main outcome measure  The percentage of trials reporting or planning to measure the rheumatoid arthritis core outcome set calculated from the information presented in the trial registry and compared with the percentage reporting the rheumatoid arthritis core outcome set in the resulting trial publications. Results  The full rheumatoid arthritis core outcome set was reported in 81% (116/143) of trials identified on the registry as completed (or terminated) for which results were found in either the published literature or the registry. For trials identified on the registry as completed (or terminated), using information only available in the registry gives an estimate for uptake of 77% (145/189). Conclusions  The uptake of the rheumatoid arthritis core outcome set in clinical trials has continued to increase over time. Using the information on outcomes listed for completed or terminated studies in a trial registry provides a reasonable estimate of the uptake of a core outcome set and is a more efficient and up-to-date approach than examining the outcomes in published trial reports. The method proposed may provide an efficient approach for an up-to-date assessment of the uptake of the 300 core outcome sets already published. 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.

Study to assess the effect of a structured communication approach on quality of life in secure mental health settings (Comquol): study protocol for a pilot cluster randomized trial.

PubMed

MacInnes, Douglas; Kinane, Catherine; Beer, Dominic; Parrott, Janet; Craig, Tom; Eldridge, Sandra; Marsh, Ian; Krotofil, Joanna; Priebe, Stefan

2013-08-16

Forensic mental health services have largely ignored examining patients' views on the nature of the services offered to them. A structured communication approach (DIALOG) has been developed with the aim of placing the patient's perspective on their care at the heart of the discussions between patients and clinicians. The effectiveness of the structured communication approach in community mental health services has been demonstrated, but no trial has taken place in a secure psychiatric setting. This pilot study is evaluating a 6-month intervention combining DIALOG with principles of solution-focused therapy on quality of life in medium-secure settings. A cluster randomized controlled trial design is being employed to conduct a 36-month pilot study. Participants are recruited from six medium-secure inpatient services, with 48 patients in the intervention group and 48 in the control group. The intervention uses a structured communication approach. It comprises six meetings between patient and nurse held monthly over a 6-month period. During each meeting, patients rate their satisfaction with a range of life and treatment domains with responses displayed on a tablet. The rating is followed by a discussion of how to improve the current situation in those domains identified by the patient. Assessments take place prior to the intervention (baseline), at 6 months (postintervention) and at 12 months (follow-up). The primary outcome is the patient's self-reported quality of life. This study aims to (1) establish the feasibility of the trial design as the basis for determining the viability of a large full-scale trial, (2) determine the variability of the outcomes of interest (quality of life, levels of satisfaction, disturbance, ward climate and engagement with services), (3) estimate the costs of the intervention and (4) refine the intervention following the outcome of the study based upon the experiences of the nurses and patients. The intervention allows patients to have a greater say in how they are treated and targets care in areas that patients identify as important to them. It is intended to establish systems that support meaningful patient and caregiver involvement and participation. Current Controlled Trials, ISRCTN34145189.

Granger causality analysis reveals distinct spatio-temporal connectivity patterns in motor and perceptual visuo-spatial working memory.

PubMed

Protopapa, Foteini; Siettos, Constantinos I; Evdokimidis, Ioannis; Smyrnis, Nikolaos

2014-01-01

We employed spectral Granger causality analysis on a full set of 56 electroencephalographic recordings acquired during the execution of either a 2D movement pointing or a perceptual (yes/no) change detection task with memory and non-memory conditions. On the basis of network characteristics across frequency bands, we provide evidence for the full dissociation of the corresponding cognitive processes. Movement-memory trial types exhibited higher degree nodes during the first 2 s of the delay period, mainly at central, left frontal and right-parietal areas. Change detection-memory trial types resulted in a three-peak temporal pattern of the total degree with higher degree nodes emerging mainly at central, right frontal, and occipital areas. Functional connectivity networks resulting from non-memory trial types were characterized by more sparse structures for both tasks. The movement-memory trial types encompassed an apparent coarse flow from frontal to parietal areas while the opposite flow from occipital, parietal to central and frontal areas was evident for the change detection-memory trial types. The differences among tasks and conditions were more profound in α (8-12 Hz) and β (12-30 Hz) and less in γ (30-45 Hz) band. Our results favor the hypothesis which considers spatial working memory as a by-product of specific mental processes that engages common brain areas under different network organizations.

Effective empirical corrections for basis set superposition error in the def2-SVPD basis: gCP and DFT-C

NASA Astrophysics Data System (ADS)

Witte, Jonathon; Neaton, Jeffrey B.; Head-Gordon, Martin

2017-06-01

With the aim of mitigating the basis set error in density functional theory (DFT) calculations employing local basis sets, we herein develop two empirical corrections for basis set superposition error (BSSE) in the def2-SVPD basis, a basis which—when stripped of BSSE—is capable of providing near-complete-basis DFT results for non-covalent interactions. Specifically, we adapt the existing pairwise geometrical counterpoise (gCP) approach to the def2-SVPD basis, and we develop a beyond-pairwise approach, DFT-C, which we parameterize across a small set of intermolecular interactions. Both gCP and DFT-C are evaluated against the traditional Boys-Bernardi counterpoise correction across a set of 3402 non-covalent binding energies and isomerization energies. We find that the DFT-C method represents a significant improvement over gCP, particularly for non-covalently-interacting molecular clusters. Moreover, DFT-C is transferable among density functionals and can be combined with existing functionals—such as B97M-V—to recover large-basis results at a fraction of the cost.

Electrophysiological revelations of trial history effects in a color oddball search task.

PubMed

Shin, Eunsam; Chong, Sang Chul

2016-12-01

In visual oddball search tasks, viewing a no-target scene (i.e., no-target selection trial) leads to the facilitation or delay of the search time for a target in a subsequent trial. Presumably, this selection failure leads to biasing attentional set and prioritizing stimulus features unseen in the no-target scene. We observed attention-related ERP components and tracked the course of attentional biasing as a function of trial history. Participants were instructed to identify color oddballs (i.e., targets) shown in varied trial sequences. The number of no-target scenes preceding a target scene was increased from zero to two to reinforce attentional biasing, and colors presented in two successive no-target scenes were repeated or changed to systematically bias attention to specific colors. For the no-target scenes, the presentation of a second no-target scene resulted in an early selection of, and sustained attention to, the changed colors (mirrored in the frontal selection positivity, the anterior N2, and the P3b). For the target scenes, the N2pc indicated an earlier allocation of attention to the targets with unseen or remotely seen colors. Inhibitory control of attention, shown in the anterior N2, was greatest when the target scene was followed by repeated no-target scenes with repeated colors. Finally, search times and the P3b were influenced by both color previewing and its history. The current results demonstrate that attentional biasing can occur on a trial-by-trial basis and be influenced by both feature previewing and its history. © 2016 Society for Psychophysiological Research.

Fixed-node diffusion Monte Carlo potential energy curve of the fluorine molecule F{sub 2} using selected configuration interaction trial wavefunctions

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

Giner, Emmanuel; Scemama, Anthony; Caffarel, Michel

2015-01-28

The potential energy curve of the F{sub 2} molecule is calculated with Fixed-Node Diffusion Monte Carlo (FN-DMC) using Configuration Interaction (CI)-type trial wavefunctions. To keep the number of determinants reasonable and thus make FN-DMC calculations feasible in practice, the CI expansion is restricted to those determinants that contribute the most to the total energy. The selection of the determinants is made using the CIPSI approach (Configuration Interaction using a Perturbative Selection made Iteratively). The trial wavefunction used in FN-DMC is directly issued from the deterministic CI program; no Jastrow factor is used and no preliminary multi-parameter stochastic optimization of themore » trial wavefunction is performed. The nodes of CIPSI wavefunctions are found to reduce significantly the fixed-node error and to be systematically improved upon increasing the number of selected determinants. To reduce the non-parallelism error of the potential energy curve, a scheme based on the use of a R-dependent number of determinants is introduced. Using Dunning’s cc-pVDZ basis set, the FN-DMC energy curve of F{sub 2} is found to be of a quality similar to that obtained with full configuration interaction/cc-pVQZ.« less

Sharing the trousers: gender roles and relationships in an HIV-prevention trial in Zimbabwe.

PubMed

Montgomery, Elizabeth T; Chidanyika, Agnes; Chipato, Tsungai; van der Straten, Ariane

2012-01-01

Male and female gender roles and inequalities are important in contributing to the disproportionate burden of HIV experienced by women in sub-Saharan Africa. Within the context of an HIV prevention trial, we aimed to describe and understand male partner influence on women's use of HIV-prevention methods. Our presumption was not that regressive gender norms prevailed - rather, that a wide range of gendered attitudes and dynamics would be expressed among couples. Data from 16 focus groups with Zimbabwean female trial participants and their male partners and 4 in-depth couples interviews were collected, and form the basis of the analysis. Findings offer descriptions of how couples have adapted techniques for negotiating modern household economies and sexual decision-making in a manner that both preserves traditional gender roles, while accommodating women's entrance into new domains such as the workforce or an HIV-prevention trial. Women's agency to introduce novel female-initiated-method use into her intimate relationships is described. Men and women's accounts of method introduction and use suggest different perceptions about the locus of sexual decision making. The study provides unique insight into a gendered context that is dynamic yet sensitive to change, which in turn can provide useful information to more appropriately guide HIV-prevention activities in this setting.

Quantum Dynamics with Short-Time Trajectories and Minimal Adaptive Basis Sets.

PubMed

Saller, Maximilian A C; Habershon, Scott

2017-07-11

Methods for solving the time-dependent Schrödinger equation via basis set expansion of the wave function can generally be categorized as having either static (time-independent) or dynamic (time-dependent) basis functions. We have recently introduced an alternative simulation approach which represents a middle road between these two extremes, employing dynamic (classical-like) trajectories to create a static basis set of Gaussian wavepackets in regions of phase-space relevant to future propagation of the wave function [J. Chem. Theory Comput., 11, 8 (2015)]. Here, we propose and test a modification of our methodology which aims to reduce the size of basis sets generated in our original scheme. In particular, we employ short-time classical trajectories to continuously generate new basis functions for short-time quantum propagation of the wave function; to avoid the continued growth of the basis set describing the time-dependent wave function, we employ Matching Pursuit to periodically minimize the number of basis functions required to accurately describe the wave function. Overall, this approach generates a basis set which is adapted to evolution of the wave function while also being as small as possible. In applications to challenging benchmark problems, namely a 4-dimensional model of photoexcited pyrazine and three different double-well tunnelling problems, we find that our new scheme enables accurate wave function propagation with basis sets which are around an order-of-magnitude smaller than our original trajectory-guided basis set methodology, highlighting the benefits of adaptive strategies for wave function propagation.

Polarization functions for the modified m6-31G basis sets for atoms Ga through Kr.

PubMed

Mitin, Alexander V

2013-09-05

The 2df polarization functions for the modified m6-31G basis sets of the third-row atoms Ga through Kr (Int J Quantum Chem, 2007, 107, 3028; Int J. Quantum Chem, 2009, 109, 1158) are proposed. The performances of the m6-31G, m6-31G(d,p), and m6-31G(2df,p) basis sets were examined in molecular calculations carried out by the density functional theory (DFT) method with B3LYP hybrid functional, Møller-Plesset perturbation theory of the second order (MP2), quadratic configuration interaction method with single and double substitutions and were compared with those for the known 6-31G basis sets as well as with the other similar 641 and 6-311G basis sets with and without polarization functions. Obtained results have shown that the performances of the m6-31G, m6-31G(d,p), and m6-31G(2df,p) basis sets are better in comparison with the performances of the known 6-31G, 6-31G(d,p) and 6-31G(2df,p) basis sets. These improvements are mainly reached due to better approximations of different electrons belonging to the different atomic shells in the modified basis sets. Applicability of the modified basis sets in thermochemical calculations is also discussed. © 2013 Wiley Periodicals, Inc.

Core journals that publish clinical trials of physical therapy interventions.

PubMed

Costa, Leonardo Oliveira Pena; Moseley, Anne M; Sherrington, Catherine; Maher, Christopher G; Herbert, Robert D; Elkins, Mark R

2010-11-01

The objective of this study was to identify core journals in physical therapy by identifying those that publish the most randomized controlled trials of physical therapy interventions, provide the highest-quality reports of randomized controlled trials, and have the highest journal impact factors. This study was an audit of a bibliographic database. All trials indexed in the Physiotherapy Evidence Database (PEDro) were analyzed. Journals that had published at least 80 trials were selected. The journals were ranked in 4 ways: number of trials published; mean total PEDro score of the trials published in the journal, regardless of publication year; mean total PEDro score of the trials published in the journal from 2000 to 2009; and 2008 journal impact factor. The top 5 core journals in physical therapy, ranked by the total number of trials published, were Archives of Physical Medicine and Rehabilitation, Clinical Rehabilitation, Spine, British Medical Journal (BMJ), and Chest. When the mean total PEDro score was used as the ranking criterion, the top 5 journals were Journal of Physiotherapy, Journal of the American Medical Association (JAMA), Stroke, Spine, and Clinical Rehabilitation. When the mean total PEDro score of the trials published from 2000 to 2009 was used as the ranking criterion, the top 5 journals were Journal of Physiotherapy, JAMA, Lancet, BMJ, and Pain. The most highly ranked physical therapy-specific journals were Physical Therapy (ranked eighth on the basis of the number of trials published) and Journal of Physiotherapy (ranked first on the basis of the quality of trials). Finally, when the 2008 impact factor was used for ranking, the top 5 journals were JAMA, Lancet, BMJ, American Journal of Respiratory and Critical Care Medicine, and Thorax. There were no significant relationships among the rankings on the basis of trial quality, number of trials, or journal impact factor. Physical therapists who are trying to keep up-to-date by reading the best available evidence on the effects of physical therapy interventions have to read more broadly than just physical therapy-specific journals. Readers of articles on physical therapy trials should be aware that high-quality trials are not necessarily published in journals with high impact factors.

Effects of dopamine D1 receptor blockade in the prelimbic prefrontal cortex or lateral dorsal striatum on frontostriatal function in Wistar and Spontaneously Hypertensive Rats.

PubMed

Gauthier, Jamie M; Tassin, David H; Dwoskin, Linda P; Kantak, Kathleen M

2014-07-15

Attention Deficit Hyperactivity Disorder (ADHD) is associated with dysfunctional prefrontal and striatal circuitry and dysregulated dopamine neurotransmission. Spontaneously Hypertensive Rats (SHR), a heuristically useful animal model of ADHD, were evaluated against normotensive Wistar (WIS) controls to determine whether dopamine D1 receptor blockade of either prelimbic prefrontal cortex (plPFC) or lateral dorsal striatum (lDST) altered learning functions of both interconnected sites. A strategy set shifting task measured plPFC function (behavioral flexibility/executive function) and a reward devaluation task measured lDST function (habitual responding). Prior to tests, rats received bilateral infusions of SCH 23390 (1.0 μg/side) or vehicle into plPFC or lDST. Following vehicle, SHR exhibited longer lever press reaction times, more trial omissions, and fewer completed trials during the set shift test compared to WIS, indicating slower decision-making and attentional/motivational impairment in SHR. After reward devaluation, vehicle-treated SHR responded less than WIS, indicating relatively less habitual responding in SHR. After SCH 23390 infusions into plPFC, WIS expressed the same behavioral phenotype as vehicle-treated SHR during set shift and reward devaluation tests. In SHR, SCH 23390 infusions into plPFC exacerbated behavioral deficits in the set shift test and maintained the lower rate of responding in the reward devaluation test. SCH 23390 infusions into lDST did not modify set shifting in either strain, but produced lower rates of responding than vehicle infusions after reward devaluation in WIS. This research provides pharmacological evidence for unidirectional interactions between prefrontal and striatal brain regions, which has implications for the neurological basis of ADHD and its treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

Genetic correlates of insight in schizophrenia.

PubMed

Xavier, Rose Mary; Vorderstrasse, Allison; Keefe, Richard S E; Dungan, Jennifer R

2018-05-01

Insight in schizophrenia is clinically important as it is associated with several adverse outcomes. Genetic contributions to insight are unknown. We examined genetic contributions to insight by investigating if polygenic risk scores (PRS) and candidate regions were associated with insight. Schizophrenia case-only analysis of the Clinical Antipsychotics Trials of Intervention Effectiveness trial. Schizophrenia PRS was constructed using Psychiatric Genomics Consortium (PGC) leave-one out GWAS as discovery data set. For candidate regions, we selected 105 schizophrenia-associated autosomal loci and 11 schizophrenia-related oligodendrocyte genes. We used regressions to examine PRS associations and set-based testing for candidate analysis. We examined data from 730 subjects. Best-fit PRS at p-threshold of 1e-07 was associated with total insight (R 2 =0.005, P=0.05, empirical P=0.054) and treatment insight (R 2 =0.005, P=0.048, empirical P=0.048). For models that controlled for neurocognition, PRS significantly predicted treatment insight but at higher p-thresholds (0.1 to 0.5) but did not survive correction. Patients with highest polygenic burden had 5.9 times increased risk for poor insight compared to patients with lowest burden. PRS explained 3.2% (P=0.002, empirical P=0.011) of variance in poor insight. Set-based analyses identified two variants associated with poor insight- rs320703, an intergenic variant (within-set P=6e-04, FDR P=0.046) and rs1479165 in SOX2-OT (within-set P=9e-04, FDR P=0.046). To the best of our knowledge, this is the first study examining genetic basis of insight. We provide evidence for genetic contributions to impaired insight. Relevance of findings and necessity for replication are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Approaching the basis set limit for DFT calculations using an environment-adapted minimal basis with perturbation theory: Formulation, proof of concept, and a pilot implementation

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

Mao, Yuezhi; Horn, Paul R.; Mardirossian, Narbe

2016-07-28

Recently developed density functionals have good accuracy for both thermochemistry (TC) and non-covalent interactions (NC) if very large atomic orbital basis sets are used. To approach the basis set limit with potentially lower computational cost, a new self-consistent field (SCF) scheme is presented that employs minimal adaptive basis (MAB) functions. The MAB functions are optimized on each atomic site by minimizing a surrogate function. High accuracy is obtained by applying a perturbative correction (PC) to the MAB calculation, similar to dual basis approaches. Compared to exact SCF results, using this MAB-SCF (PC) approach with the same large target basis set producesmore » <0.15 kcal/mol root-mean-square deviations for most of the tested TC datasets, and <0.1 kcal/mol for most of the NC datasets. The performance of density functionals near the basis set limit can be even better reproduced. With further improvement to its implementation, MAB-SCF (PC) is a promising lower-cost substitute for conventional large-basis calculations as a method to approach the basis set limit of modern density functionals.« less

Simple and efficient LCAO basis sets for the diffuse states in carbon nanostructures.

PubMed

Papior, Nick R; Calogero, Gaetano; Brandbyge, Mads

2018-06-27

We present a simple way to describe the lowest unoccupied diffuse states in carbon nanostructures in density functional theory calculations using a minimal LCAO (linear combination of atomic orbitals) basis set. By comparing plane wave basis calculations, we show how these states can be captured by adding long-range orbitals to the standard LCAO basis sets for the extreme cases of planar sp 2 (graphene) and curved carbon (C 60 ). In particular, using Bessel functions with a long range as additional basis functions retain a minimal basis size. This provides a smaller and simpler atom-centered basis set compared to the standard pseudo-atomic orbitals (PAOs) with multiple polarization orbitals or by adding non-atom-centered states to the basis.

Simple and efficient LCAO basis sets for the diffuse states in carbon nanostructures

NASA Astrophysics Data System (ADS)

Papior, Nick R.; Calogero, Gaetano; Brandbyge, Mads

2018-06-01

We present a simple way to describe the lowest unoccupied diffuse states in carbon nanostructures in density functional theory calculations using a minimal LCAO (linear combination of atomic orbitals) basis set. By comparing plane wave basis calculations, we show how these states can be captured by adding long-range orbitals to the standard LCAO basis sets for the extreme cases of planar sp 2 (graphene) and curved carbon (C60). In particular, using Bessel functions with a long range as additional basis functions retain a minimal basis size. This provides a smaller and simpler atom-centered basis set compared to the standard pseudo-atomic orbitals (PAOs) with multiple polarization orbitals or by adding non-atom-centered states to the basis.

Trial type mixing substantially reduces the response set effect in the Stroop task.

PubMed

Hasshim, Nabil; Parris, Benjamin A

2017-03-20

The response set effect refers to the finding that an irrelevant incongruent colour-word produces greater interference when it is one of the response options (referred to as a response set trial), compared to when it is not (a non-response set trial). Despite being a key effect for models of selective attention, the magnitude of the effect varies considerably across studies. We report two within-subjects experiments that tested the hypothesis that presentation format modulates the magnitude of the response set effect. Trial types (e.g. response set, non-response set, neutral) were either presented in separate blocks (pure) or in blocks containing trials from all conditions presented randomly (mixed). In the first experiment we show that the response set effect is substantially reduced in the mixed block context as a result of a decrease in RTs to response set trials. By demonstrating the modulation of the response set effect under conditions of trial type mixing we present evidence that is difficult for models of the effect based on strategic, top-down biasing of attention to explain. In a second experiment we tested a stimulus-driven account of the response set effect by manipulating the number of colour-words that make up the non-response set of distractors. The results show that the greater the number of non-response set colour concepts, the smaller the response set effect. Alternative accounts of the data and its implications for research debating the automaticity of reading are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Core outcome sets and trial registries.

PubMed

Clarke, Mike; Williamson, Paula

2015-05-14

Some reasons for registering trials might be considered as self-serving, such as satisfying the requirements of a journal in which the researchers wish to publish their eventual findings or publicising the trial to boost recruitment. Registry entries also help others, including systematic reviewers, to know about ongoing or unpublished studies and contribute to reducing research waste by making it clear what studies are ongoing. Other sources of research waste include inconsistency in outcome measurement across trials in the same area, missing data on important outcomes from some trials, and selective reporting of outcomes. One way to reduce this waste is through the use of core outcome sets: standardised sets of outcomes for research in specific areas of health and social care. These do not restrict the outcomes that will be measured, but provide the minimum to include if a trial is to be of the most use to potential users. We propose that trial registries, such as ISRCTN, encourage researchers to note their use of a core outcome set in their entry. This will help people searching for trials and those worried about selective reporting in closed trials. Trial registries can facilitate these efforts to make new trials as useful as possible and reduce waste. The outcomes section in the entry could prompt the researcher to consider using a core outcome set and facilitate the specification of that core outcome set and its component outcomes through linking to the original core outcome set. In doing this, registries will contribute to the global effort to ensure that trials answer important uncertainties, can be brought together in systematic reviews, and better serve their ultimate aim of improving health and well-being through improving health and social care.

Derivation of a formula for the resonance integral for a nonorthogonal basis set

PubMed Central

Yim, Yung-Chang; Eyring, Henry

1981-01-01

In a self-consistent field calculation, a formula for the off-diagonal matrix elements of the core Hamiltonian is derived for a nonorthogonal basis set by a polyatomic approach. A set of parameters is then introduced for the repulsion integral formula of Mataga-Nishimoto to fit the experimental data. The matrix elements computed for the nonorthogonal basis set in the π-electron approximation are transformed to those for an orthogonal basis set by the Löwdin symmetrical orthogonalization. PMID:16593009

Hydroxychloroquine effectiveness in reducing symptoms of hand osteoarthritis (HERO): study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Osteoarthritis (OA) is the most common type of arthritis, causing significant joint pain and disability. It is already a major cause of healthcare expenditure and its incidence will further increase with the ageing population. Current treatments for OA have major limitations and new analgesic treatments are needed. Synovitis is prevalent in OA and is associated with pain. Hydroxychloroquine is used in routine practice for treating synovitis in inflammatory arthritides, such as rheumatoid arthritis. We propose that treating patients with symptomatic hand OA with hydroxychloroquine will be a practical and safe treatment to reduce synovitis and pain. Methods/design HERO is an investigator-initiated, multicentre, randomized, double-blind, placebo-controlled trial. A total of 252 subjects with symptomatic hand OA will be recruited across primary and secondary care sites in the UK and randomized on a 1:1 basis to active treatment or placebo for 12 months. Daily medication dose will range from 200 to 400 mg according to ideal body weight. The primary endpoint is change in average hand pain during the previous two weeks (measured on a numerical rating scale (NRS)) between baseline and six months. Secondary endpoints include other self-reported pain, function and quality-of-life measures and radiographic structural change at 12 months. A health economics analysis will also be performed. An ultrasound substudy will be conducted to examine baseline levels of synovitis. Linear and logistic regression will be used to compare changes between groups using univariable and multivariable modelling analyses. All analyses will be conducted on an intention-to-treat basis. Discussion The HERO trial is designed to examine whether hydroxychloroquine is an effective analgesic treatment for OA and whether it provides any long-term structural benefit. The ultrasound substudy will address whether baseline synovitis is a predictor of therapeutic response. This will potentially provide a new treatment for OA, which could be of particular use in the primary care setting. Trial registration ISRCTN91859104. PMID:23452375

Teacher-Conducted Trial-Based Functional Analyses as the Basis for Intervention

ERIC Educational Resources Information Center

Bloom, Sarah E.; Lambert, Joseph M.; Dayton, Elizabeth; Samaha, Andrew L.

2013-01-01

Previous studies have focused on whether a trial-based functional analysis (FA) yields the same outcomes as more traditional FAs, and whether interventions based on trial-based FAs can reduce socially maintained problem behavior. We included a full range of behavior functions and taught 3 teachers to conduct a trial-based FA with 3 boys with…

On the "Optimal" Choice of Trial Functions for Modelling Potential Fields

NASA Astrophysics Data System (ADS)

Michel, Volker

2015-04-01

There are many trial functions (e.g. on the sphere) available which can be used for the modelling of a potential field. Among them are orthogonal polynomials such as spherical harmonics and radial basis functions such as spline or wavelet basis functions. Their pros and cons have been widely discussed in the last decades. We present an algorithm, the Regularized Functional Matching Pursuit (RFMP), which is able to choose trial functions of different kinds in order to combine them to a stable approximation of a potential field. One main advantage of the RFMP is that the constructed approximation inherits the advantages of the different basis systems. By including spherical harmonics, coarse global structures can be represented in a sparse way. However, the additional use of spline basis functions allows a stable handling of scattered data grids. Furthermore, the inclusion of wavelets and scaling functions yields a multiscale analysis of the potential. In addition, ill-posed inverse problems (like a downward continuation or the inverse gravimetric problem) can be regularized with the algorithm. We show some numerical examples to demonstrate the possibilities which the RFMP provides.

Approximations to complete basis set-extrapolated, highly correlated non-covalent interaction energies.

PubMed

Mackie, Iain D; DiLabio, Gino A

2011-10-07

The first-principles calculation of non-covalent (particularly dispersion) interactions between molecules is a considerable challenge. In this work we studied the binding energies for ten small non-covalently bonded dimers with several combinations of correlation methods (MP2, coupled-cluster single double, coupled-cluster single double (triple) (CCSD(T))), correlation-consistent basis sets (aug-cc-pVXZ, X = D, T, Q), two-point complete basis set energy extrapolations, and counterpoise corrections. For this work, complete basis set results were estimated from averaged counterpoise and non-counterpoise-corrected CCSD(T) binding energies obtained from extrapolations with aug-cc-pVQZ and aug-cc-pVTZ basis sets. It is demonstrated that, in almost all cases, binding energies converge more rapidly to the basis set limit by averaging the counterpoise and non-counterpoise corrected values than by using either counterpoise or non-counterpoise methods alone. Examination of the effect of basis set size and electron correlation shows that the triples contribution to the CCSD(T) binding energies is fairly constant with the basis set size, with a slight underestimation with CCSD(T)∕aug-cc-pVDZ compared to the value at the (estimated) complete basis set limit, and that contributions to the binding energies obtained by MP2 generally overestimate the analogous CCSD(T) contributions. Taking these factors together, we conclude that the binding energies for non-covalently bonded systems can be accurately determined using a composite method that combines CCSD(T)∕aug-cc-pVDZ with energy corrections obtained using basis set extrapolated MP2 (utilizing aug-cc-pVQZ and aug-cc-pVTZ basis sets), if all of the components are obtained by averaging the counterpoise and non-counterpoise energies. With such an approach, binding energies for the set of ten dimers are predicted with a mean absolute deviation of 0.02 kcal/mol, a maximum absolute deviation of 0.05 kcal/mol, and a mean percent absolute deviation of only 1.7%, relative to the (estimated) complete basis set CCSD(T) results. Use of this composite approach to an additional set of eight dimers gave binding energies to within 1% of previously published high-level data. It is also shown that binding within parallel and parallel-crossed conformations of naphthalene dimer is predicted by the composite approach to be 9% greater than that previously reported in the literature. The ability of some recently developed dispersion-corrected density-functional theory methods to predict the binding energies of the set of ten small dimers was also examined. © 2011 American Institute of Physics

Communication: A novel implementation to compute MP2 correlation energies without basis set superposition errors and complete basis set extrapolation.

PubMed

Dixit, Anant; Claudot, Julien; Lebègue, Sébastien; Rocca, Dario

2017-06-07

By using a formulation based on the dynamical polarizability, we propose a novel implementation of second-order Møller-Plesset perturbation (MP2) theory within a plane wave (PW) basis set. Because of the intrinsic properties of PWs, this method is not affected by basis set superposition errors. Additionally, results are converged without relying on complete basis set extrapolation techniques; this is achieved by using the eigenvectors of the static polarizability as an auxiliary basis set to compactly and accurately represent the response functions involved in the MP2 equations. Summations over the large number of virtual states are avoided by using a formalism inspired by density functional perturbation theory, and the Lanczos algorithm is used to include dynamical effects. To demonstrate this method, applications to three weakly interacting dimers are presented.

Working memory component processes: isolating BOLD signal changes.

PubMed

Motes, Michael A; Rypma, Bart

2010-01-15

The chronology of the component processes subserving working memory (WM) and hemodynamic response lags has hindered the use of fMRI for exploring neural substrates of WM. In the present study, however, participants completed full trials that involved encoding two or six letters, maintaining the memory set over a delay, and then deciding whether a probe was in the memory set or not. Additionally, they completed encode-only, encode-and-maintain, and encode-and-decide partial trials intermixed with the full trials. The inclusion of partial trials allowed for the isolation of BOLD signal changes to the different trial periods. The results showed that only lateral and medial prefrontal cortex regions differentially responded to the 2- and 6-letter memory sets over the trial periods, showing greater activation to 6-letter sets during the encode and maintain trial periods. Thus, the data showed the differential involvement of PFC in the encoding and maintenance of supra- and sub-capacity memory sets and show the efficacy of using fMRI partial trial methods to study WM component processes.

Working Memory Component Processes: Isolating BOLD Signal-Changes

PubMed Central

Motes, Michael A.; Rypma, Bart

2009-01-01

The chronology of the component processes subserving working memory (WM) and hemodynamic response lags have hindered the use of fMRI for exploring neural substrates of WM. In the present study, however, participants completed full trials that involved encoding two or six letters, maintaining the memory-set over a delay, and then deciding whether a probe was in the memory-set or not. Additionally, they completed encode only, encode and maintain, and encode and decide partial-trials intermixed with the full-trials. The inclusion of partial-trials allowed for the isolation of BOLD signal-changes to the different trial-periods. The results showed that only lateral and medial prefrontal cortex regions differentially responded to the 2- and 6-letter memory-sets over the trial-periods, showing greater activation to 6-letter sets during the encode and maintain trial-periods. Thus, the data showed the differential involvement of PFC in the encoding and maintenance of supra- and sub-capacity memory-sets and show the efficacy of using fMRI partial-trial methods to study WM component processes. PMID:19732840

Evidence-Base Update of Psychosocial Treatments for Child and Adolescent Depression

PubMed Central

Weersing, V. Robin; Jeffreys, Megan; Do, Minh-Chau T.; Schwartz, Karen T. G.; Bolano, Carl

2017-01-01

Depression in youth is prevalent and disabling and tends to presage a chronic and recurrent course of illness and impairment in adulthood. Clinical trial research in youth depression has a 30 year history, and evidence-based treatment reviews appeared in 1998 and 2008. The current review of 42 randomized controlled trials (RCTs) updates these reviews to include RCTs published between 2008 and 2014 (N = 14) and re-evaluates previously reviewed literature. Given the growing maturity of the field, this review utilized a stringent set of methodological criteria for trial inclusion, most notable for excluding trials based in sub-clinical samples of youth that had been included in previous reviews (N = 12) and including well-designed RCTs with null and negative findings (N = 8). Findings from the current review suggest that evidence for child treatments is notably weaker than for adolescent interventions, with no child treatments achieving well-established status and the evidentiary basis of treatments downgraded from previous reports. Cognitive behavioral therapy (CBT) for clinically depressed children appears to be possibly efficacious, with mixed findings across trials. For depressed adolescents, both CBT and Interpersonal Psychotherapy (IPT) are well-established interventions, with evidence of efficacy in multiple trials by independent investigative teams. This positive conclusion is tempered by the small size of the IPT literature (N = 6) and concern that CBT effects may be attenuated in clinically complicated samples and when compared against active control conditions. In conclusion, data on predictors, moderators, and mediators are examined and priorities for future research discussed. PMID:27870579

Current challenges for clinical trials of cardiovascular medical devices.

PubMed

Zannad, Faiez; Stough, Wendy Gattis; Piña, Ileana L; Mehran, Roxana; Abraham, William T; Anker, Stefan D; De Ferrari, Gaetano M; Farb, Andrew; Geller, Nancy L; Kieval, Robert S; Linde, Cecilia; Redberg, Rita F; Stein, Kenneth; Vincent, Alphons; Woehrle, Holger; Pocock, Stuart J

2014-07-15

Several features of cardiovascular devices raise considerations for clinical trial conduct. Prospective, randomized, controlled trials remain the highest quality evidence for safety and effectiveness assessments, but, for instance, blinding may be challenging. In order to avoid bias and not confound data interpretation, the use of objective endpoints and blinding patients, study staff, core labs, and clinical endpoint committees to treatment assignment are helpful approaches. Anticipation of potential bias should be considered and planned for prospectively in a cardiovascular device trial. Prospective, single-arm studies (often referred to as registry studies) can provide additional data in some cases. They are subject to selection bias even when carefully designed; thus, they are generally not acceptable as the sole basis for pre-market approval of high risk cardiovascular devices. However, they complement the evidence base and fill the gaps unanswered by randomized trials. Registry studies present device safety and effectiveness in day-to-day clinical practice settings and detect rare adverse events in the post-market period. No single research design will be appropriate for every cardiovascular device or target patient population. The type of trial, appropriate control group, and optimal length of follow-up will depend on the specific device, its potential clinical benefits, the target patient population and the existence (or lack) of effective therapies, and its anticipated risks. Continued efforts on the part of investigators, the device industry, and government regulators are needed to reach the optimal approach for evaluating the safety and performance of innovative devices for the treatment of cardiovascular disease. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Correlation consistent valence basis sets for use with the Stuttgart-Dresden-Bonn relativistic effective core potentials: The atoms Ga-Kr and In-Xe

NASA Astrophysics Data System (ADS)

Martin, Jan M. L.; Sundermann, Andreas

2001-02-01

We propose large-core correlation-consistent (cc) pseudopotential basis sets for the heavy p-block elements Ga-Kr and In-Xe. The basis sets are of cc-pVTZ and cc-pVQZ quality, and have been optimized for use with the large-core (valence-electrons only) Stuttgart-Dresden-Bonn (SDB) relativistic pseudopotentials. Validation calculations on a variety of third-row and fourth-row diatomics suggest them to be comparable in quality to the all-electron cc-pVTZ and cc-pVQZ basis sets for lighter elements. Especially the SDB-cc-pVQZ basis set in conjunction with a core polarization potential (CPP) yields excellent agreement with experiment for compounds of the later heavy p-block elements. For accurate calculations on Ga (and, to a lesser extent, Ge) compounds, explicit treatment of 13 valence electrons appears to be desirable, while it seems inevitable for In compounds. For Ga and Ge, we propose correlation consistent basis sets extended for (3d) correlation. For accurate calculations on organometallic complexes of interest to homogenous catalysis, we recommend a combination of the standard cc-pVTZ basis set for first- and second-row elements, the presently derived SDB-cc-pVTZ basis set for heavier p-block elements, and for transition metals, the small-core [6s5p3d] Stuttgart-Dresden basis set-relativistic effective core potential combination supplemented by (2f1g) functions with exponents given in the Appendix to the present paper.

Vowel Imagery Decoding toward Silent Speech BCI Using Extreme Learning Machine with Electroencephalogram

PubMed Central

Kim, Jongin; Park, Hyeong-jun

2016-01-01

The purpose of this study is to classify EEG data on imagined speech in a single trial. We recorded EEG data while five subjects imagined different vowels, /a/, /e/, /i/, /o/, and /u/. We divided each single trial dataset into thirty segments and extracted features (mean, variance, standard deviation, and skewness) from all segments. To reduce the dimension of the feature vector, we applied a feature selection algorithm based on the sparse regression model. These features were classified using a support vector machine with a radial basis function kernel, an extreme learning machine, and two variants of an extreme learning machine with different kernels. Because each single trial consisted of thirty segments, our algorithm decided the label of the single trial by selecting the most frequent output among the outputs of the thirty segments. As a result, we observed that the extreme learning machine and its variants achieved better classification rates than the support vector machine with a radial basis function kernel and linear discrimination analysis. Thus, our results suggested that EEG responses to imagined speech could be successfully classified in a single trial using an extreme learning machine with a radial basis function and linear kernel. This study with classification of imagined speech might contribute to the development of silent speech BCI systems. PMID:28097128

Hybrid Grid and Basis Set Approach to Quantum Chemistry DMRG

NASA Astrophysics Data System (ADS)

Stoudenmire, Edwin Miles; White, Steven

We present a new approach for using DMRG for quantum chemistry that combines the advantages of a basis set with that of a grid approximation. Because DMRG scales linearly for quasi-one-dimensional systems, it is feasible to approximate the continuum with a fine grid in one direction while using a standard basis set approach for the transverse directions. Compared to standard basis set methods, we reach larger systems and achieve better scaling when approaching the basis set limit. The flexibility and reduced costs of our approach even make it feasible to incoporate advanced DMRG techniques such as simulating real-time dynamics. Supported by the Simons Collaboration on the Many-Electron Problem.

Low-molecular-weight heparins: pharmacologic profile and product differentiation.

PubMed

Fareed, J; Jeske, W; Hoppensteadt, D; Clarizio, R; Walenga, J M

1998-09-10

The interchangeability of low-molecular-weight heparins (LMWHs) has been the subject of discussion since these products were first introduced for the prophylaxis of deep vein thrombosis. Experimental evidence now exists to show that LMWHs differ from each other in a number of characteristics. Products have been differentiated on the basis of molecular weight and biologic properties, but only limited information derived from the clinical setting is available. Potency has been described on the basis of anti-Factor Xa activity, but at equivalent anti-Xa activities, the anti-Factor IIa activity of different products shows marked variations. At the relatively small doses used for the management of postsurgical deep vein thrombosis, the effect of these interproduct differences may be relatively minor, but as LMWHs are developed for therapeutic use at much higher doses, such differences may become clinically important. Variations in safety and efficacy reported in clinical trials of LMWHs may reflect the known differences in their molecular composition and pharmacologic properties.

Density functional theory calculations of the lowest energy quintet and triplet states of model hemes: role of functional, basis set, and zero-point energy corrections.

PubMed

Khvostichenko, Daria; Choi, Andrew; Boulatov, Roman

2008-04-24

We investigated the effect of several computational variables, including the choice of the basis set, application of symmetry constraints, and zero-point energy (ZPE) corrections, on the structural parameters and predicted ground electronic state of model 5-coordinate hemes (iron(II) porphines axially coordinated by a single imidazole or 2-methylimidazole). We studied the performance of B3LYP and B3PW91 with eight Pople-style basis sets (up to 6-311+G*) and B97-1, OLYP, and TPSS functionals with 6-31G and 6-31G* basis sets. Only hybrid functionals B3LYP, B3PW91, and B97-1 reproduced the quintet ground state of the model hemes. With a given functional, the choice of the basis set caused up to 2.7 kcal/mol variation of the quintet-triplet electronic energy gap (DeltaEel), in several cases, resulting in the inversion of the sign of DeltaEel. Single-point energy calculations with triple-zeta basis sets of the Pople (up to 6-311G++(2d,2p)), Ahlrichs (TZVP and TZVPP), and Dunning (cc-pVTZ) families showed the same trend. The zero-point energy of the quintet state was approximately 1 kcal/mol lower than that of the triplet, and accounting for ZPE corrections was crucial for establishing the ground state if the electronic energy of the triplet state was approximately 1 kcal/mol less than that of the quintet. Within a given model chemistry, effects of symmetry constraints and of a "tense" structure of the iron porphine fragment coordinated to 2-methylimidazole on DeltaEel were limited to 0.3 kcal/mol. For both model hemes the best agreement with crystallographic structural data was achieved with small 6-31G and 6-31G* basis sets. Deviation of the computed frequency of the Fe-Im stretching mode from the experimental value with the basis set decreased in the order: nonaugmented basis sets, basis sets with polarization functions, and basis sets with polarization and diffuse functions. Contraction of Pople-style basis sets (double-zeta or triple-zeta) affected the results insignificantly for iron(II) porphyrin coordinated with imidazole. Poor performance of a "locally dense" basis set with a large number of basis functions on the Fe center was observed in calculation of quintet-triplet gaps. Our results lead to a series of suggestions for density functional theory calculations of quintet-triplet energy gaps in ferrohemes with a single axial imidazole; these suggestions are potentially applicable for other transition-metal complexes.

Radiological Medical Device Innovation: Approvals via the Premarket Approval Pathway From 2000 to 2015.

PubMed

Ghobadi, Comeron W; Hayman, Emily L; Finkle, Joshua H; Walter, Jessica R; Xu, Shuai

2017-01-01

The aim of this study was to critically assess the clinical evidence leading to radiologic medical device approvals via the premarket approval pathway from 2000 to 2015. This study used the publically available FDA premarket database for radiologic device approvals over the past 15 years (September 1, 2000, to August 31, 2015). Approval characteristics were collected for each device, and statistical analysis was performed on the data for each pivotal trial. Additionally, methodological quality of the pivotal trial was determined using the Quality Assessment of Diagnostic Accuracy Studies tool. Twenty-three class III radiologic device approvals were identified, with breast imaging accounting for 16 (70%) and computer-aided detection software accounting for 9 (39%) approvals. The median premarket approval time was 475 days (range, 180-1,116). Twenty-one devices were approved on the basis of multireader, multicenter studies, one on the basis of a randomized controlled trial, and one on the basis of a preclinical technical equivalence trial. The median number of patients per pivotal trial was 201 (range, 25-3,946). Twenty-six of the 34 pivotal trials (76%) had at least one methodologic bias. Breast imaging devices had a greater number of patients per pivotal trial (P = .009) and more prospective studies. With regard to all modalities, increased time to device approval correlated with weaker trial quality (r = 0.600, P < .001). Radiologic devices are largely approved by multireader, multicenter studies, the recommended standard for assessing diagnostic technologies. Given that radiologic devices play a key role in modern medicine, further efforts should be made to increase transparency of clinical data leading to approval. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

The Harmonizing Outcome Measures for Eczema (HOME) roadmap: a methodological framework to develop core sets of outcome measurements in dermatology.

PubMed

Schmitt, Jochen; Apfelbacher, Christian; Spuls, Phyllis I; Thomas, Kim S; Simpson, Eric L; Furue, Masutaka; Chalmers, Joanne; Williams, Hywel C

2015-01-01

Core outcome sets (COSs) are consensus-derived minimum sets of outcomes to be assessed in a specific situation. COSs are being increasingly developed to limit outcome-reporting bias, allow comparisons across trials, and strengthen clinical decision making. Despite the increasing interest in outcomes research, methods to develop COSs have not yet been standardized. The aim of this paper is to present the Harmonizing Outcomes Measures for Eczema (HOME) roadmap for the development and implementation of COSs, which was developed on the basis of our experience in the standardization of outcome measurements for atopic eczema. Following the establishment of a panel representing all relevant stakeholders and a research team experienced in outcomes research, the scope and setting of the core set should be defined. The next steps are the definition of a core set of outcome domains such as symptoms or quality of life, followed by the identification or development and validation of appropriate outcome measurement instruments to measure these core domains. Finally, the consented COS needs to be disseminated, implemented, and reviewed. We believe that the HOME roadmap is a useful methodological framework to develop COSs in dermatology, with the ultimate goal of better decision making and promoting patient-centered health care.

Analysing malaria drug trials on a per-individual or per-clone basis: a comparison of methods.

PubMed

Jaki, Thomas; Parry, Alice; Winter, Katherine; Hastings, Ian

2013-07-30

There are a variety of methods used to estimate the effectiveness of antimalarial drugs in clinical trials, invariably on a per-person basis. A person, however, may have more than one malaria infection present at the time of treatment. We evaluate currently used methods for analysing malaria trials on a per-individual basis and introduce a novel method to estimate the cure rate on a per-infection (clone) basis. We used simulated and real data to highlight the differences of the various methods. We give special attention to classifying outcomes as cured, recrudescent (infections that never fully cleared) or ambiguous on the basis of genetic markers at three loci. To estimate cure rates on a per-clone basis, we used the genetic information within an individual before treatment to determine the number of clones present. We used the genetic information obtained at the time of treatment failure to classify clones as recrudescence or new infections. On the per-individual level, we find that the most accurate methods of classification label an individual as newly infected if all alleles are different at the beginning and at the time of failure and as a recrudescence if all or some alleles were the same. The most appropriate analysis method is survival analysis or alternatively for complete data/per-protocol analysis a proportion estimate that treats new infections as successes. We show that the analysis of drug effectiveness on a per-clone basis estimates the cure rate accurately and allows more detailed evaluation of the performance of the treatment. Copyright © 2012 John Wiley & Sons, Ltd.

Localized basis sets for unbound electrons in nanoelectronics.

PubMed

Soriano, D; Jacob, D; Palacios, J J

2008-02-21

It is shown how unbound electron wave functions can be expanded in a suitably chosen localized basis sets for any desired range of energies. In particular, we focus on the use of Gaussian basis sets, commonly used in first-principles codes. The possible usefulness of these basis sets in a first-principles description of field emission or scanning tunneling microscopy at large bias is illustrated by studying a simpler related phenomenon: The lifetime of an electron in a H atom subjected to a strong electric field.

Bibliography of Mock Trial Materials.

ERIC Educational Resources Information Center

National Inst. for Citizen Education in the Law, Washington, DC.

This catalog lists general articles on mock trials, information for arranging mock trial competitions, mock trial problem sets, and video tapes. The problem sets contain introductory material, applicable law, statements of facts, witness statements, and documents. The cases include issues in family, consumer, criminal, and immigration law. Several…

Near Hartree-Fock quality GTO basis sets for the second-row atoms

NASA Technical Reports Server (NTRS)

Partridge, Harry

1987-01-01

Energy optimized, near Hartree-Fock quality Gaussian basis sets ranging in size from (17s12p) to (20s15p) are presented for the ground states of the second-row atoms for Na(2P), Na(+), Na(-), Mg(3P), P(-), S(-), and Cl(-). In addition, optimized supplementary functions are given for the ground state basis sets to describe the negative ions, and the excited Na(2P) and Mg(3P) atomic states. The ratios of successive orbital exponents describing the inner part of the 1s and 2p orbitals are found to be nearly independent of both nuclear charge and basis set size. This provides a method of obtaining good starting estimates for other basis set optimizations.

Finding a needle in a haystack: toward a psychologically informed method for aviation security screening.

PubMed

Ormerod, Thomas C; Dando, Coral J

2015-02-01

Current aviation security systems identify behavioral indicators of deception to assess risks to flights, but they lack a strong psychological basis or empirical validation. We present a new method that tests the veracity of passenger accounts. In an in vivo double-blind randomized-control trial conducted in international airports, security agents detected 66% of deceptive passengers using the veracity test method compared with less than 5% using behavioral indicator recognition. As well as revealing advantages of veracity testing over behavioral indicator identification, the study provides the highest levels to date of deception detection in a realistic setting where the known base rate of deceptive individuals is low.

Relativistic Prolapse-Free Gaussian Basis Sets of Quadruple-ζ Quality: (aug-)RPF-4Z. III. The f-Block Elements.

PubMed

Teodoro, Tiago Quevedo; Visscher, Lucas; da Silva, Albérico Borges Ferreira; Haiduke, Roberto Luiz Andrade

2017-03-14

The f-block elements are addressed in this third part of a series of prolapse-free basis sets of quadruple-ζ quality (RPF-4Z). Relativistic adapted Gaussian basis sets (RAGBSs) are used as primitive sets of functions while correlating/polarization (C/P) functions are chosen by analyzing energy lowerings upon basis set increments in Dirac-Coulomb multireference configuration interaction calculations with single and double excitations of the valence spinors. These function exponents are obtained by applying the RAGBS parameters in a polynomial expression. Moreover, through the choice of C/P characteristic exponents from functions of lower angular momentum spaces, a reduction in the computational demand is attained in relativistic calculations based on the kinetic balance condition. The present study thus complements the RPF-4Z sets for the whole periodic table (Z ≤ 118). The sets are available as Supporting Information and can also be found at http://basis-sets.iqsc.usp.br .

Combination of large and small basis sets in electronic structure calculations on large systems

NASA Astrophysics Data System (ADS)

Røeggen, Inge; Gao, Bin

2018-04-01

Two basis sets—a large and a small one—are associated with each nucleus of the system. Each atom has its own separate one-electron basis comprising the large basis set of the atom in question and the small basis sets for the partner atoms in the complex. The perturbed atoms in molecules and solids model is at core of the approach since it allows for the definition of perturbed atoms in a system. It is argued that this basis set approach should be particularly useful for periodic systems. Test calculations are performed on one-dimensional arrays of H and Li atoms. The ground-state energy per atom in the linear H array is determined versus bond length.

Goal-setting, self-efficacy, and memory performance in older and younger adults.

PubMed

West, R L; Thorn, R M

2001-01-01

Research in field and laboratory settings has shown that goals lead to improved self-efficacy and performance, especially when individuals also receive positive feedback. The present study extended goal-setting theory to examine self-set goals and feedback in relation to younger and older adults' memory performance and self-efficacy. Following a baseline recall trial, participants completed three shopping list recall trials. Half of the participants were instructed to set goals for the three experimental trials, and half in each goal condition received performance feedback after each trial. Young adults' self-efficacy, clustering, and recall exceeded that of older adults. Goal setting increased self-efficacy for younger but not older adults, and it did not affect performance. Younger adults and participants in the feedback condition increased their goals across trials, as did participants for whom feedback indicated success. These data provide a first look at the motivational impact of feedback and self-set recall goals in memory aging. Additional study is needed to understand the interactive effects of type of feedback, memory task difficulty, and type of goal setting at different ages.

The efficacy and safety of Baoji Tablets for treating common cold with summer-heat and dampness syndrome: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Despite the high incidence and the economic impact of the common cold, there are still no effective therapeutic options available. Although traditional Chinese medicine (TCM) is widely used in China to treat the common cold, there is still a lack of high-quality clinical trials. This article sets forth the protocol for a high-quality trial of a new TCM drug, Baoji Tablets, which is designed to treat the common cold with summer-heat and dampness syndrome (CCSDS). The trial is evaluating both the efficacy and safety of Baoji Tablets. Methods/design This study is designed as a multicenter, phase II, parallel-group, double-blind, double-dummy, randomized and placebo-controlled trial. A total of 288 patients will be recruited from four centers. The new tablets group are administered Baoji Tablets 0.9 g and dummy Baoji Pills 3.7 g. The old pills group are administered dummy Baoji Tablets 0.9 g and Baoji Pills 3.7 g. The placebo control group are administered dummy Baoji Tablets 0.9 g and dummy Baoji Pills 3.7 g. All drugs are taken three times daily for 3 days. The primary outcome is the duration of all symptoms. Secondary outcomes include the duration of primary and secondary symptoms, changes in primary and secondary symptom scores and cumulative symptom score at day 4, as well as an evaluation of treatment efficacy. Discussion This is the first multicenter, double-blind, double-dummy, randomized and placebo-controlled trial designated to treat CCSDS in an adult population from China. It will establish the basis for a scientific and objective assessment of the efficacy and safety of Baoji Tablets for treating CCSDS, and provide evidence for a phase III clinical trial. Trial registration This study is registered with the Chinese Clinical Trial Registry. The registration number is ChiCTR-TRC-13003197. PMID:24359521

32 CFR 644.117 - Procedure prior to trial.

Code of Federal Regulations, 2010 CFR

2010-07-01

... personnel without the knowledge and consent of the United States Attorney. If the property owner is... proceeding, it is desirable to settle by stipulation, or to go to trial, on the “unit” basis. Many United... that the Corps has full knowledge of the appraisal reports on which settlement negotiations or trial...

75 FR 73109 - Guidance for Industry on Antibacterial Drug Products: Use of Noninferiority Trials to Support...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-29

... noninferiority (NI) clinical trial designs to evaluate antibacterial drug products. The Agency's thinking in this...-controlled trials designed to show NI as the basis for approval of antibacterial drug products. This guidance... to inform industry, sponsors, applicants, researchers, and the public on the appropriate uses of NI...

77 FR 48611 - Rules of Practice for Trials Before the Patent Trial and Appeal Board and Judicial Review of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-14

... consolidated set of rules relating to Board trial practice for inter partes review, post-grant review, the... rules relating to Board trial practice for inter partes review, post- grant review, the transitional...), to provide a consolidated set of rules relating to Board trial practice for inter partes review, post...

[Categorization in infancy: differentiation of global object classes].

PubMed

Pauen, S

1996-01-01

Two studies tested whether preverbal children distinguish global categories (animal and furniture) on a conceptual basis. A total of 59 eleven-month-olds solved an object examination task. During habituation, infants freely explored different natural-looking toy models from the same category. In Study 1, the same series of four different examplars was presented twice. In Study 2, ten different exemplares were presented. In both cases, a significant habituation effect could be observed. When a perceptually new object of the same category was presented on the first test trial after habituation, a significant increase in examination time from the last habituation trial to the first test trial could be observed in Study 1. When a new object of the contrasting category was presented on the second test trial, examination times increased significantly from the first to the second test trial in both studies. These results support earlier findings suggesting that preverbal infants are able to distinguish global categories on a conceptual basis.

On basis set superposition error corrected stabilization energies for large n-body clusters.

PubMed

Walczak, Katarzyna; Friedrich, Joachim; Dolg, Michael

2011-10-07

In this contribution, we propose an approximate basis set superposition error (BSSE) correction scheme for the site-site function counterpoise and for the Valiron-Mayer function counterpoise correction of second order to account for the basis set superposition error in clusters with a large number of subunits. The accuracy of the proposed scheme has been investigated for a water cluster series at the CCSD(T), CCSD, MP2, and self-consistent field levels of theory using Dunning's correlation consistent basis sets. The BSSE corrected stabilization energies for a series of water clusters are presented. A study regarding the possible savings with respect to computational resources has been carried out as well as a monitoring of the basis set dependence of the approximate BSSE corrections. © 2011 American Institute of Physics

Pilot climate data system: A state-of-the-art capability in scientific data management

NASA Technical Reports Server (NTRS)

Smith, P. H.; Treinish, L. A.; Novak, L. V.

1983-01-01

The Pilot Climate Data System (PCDS) was developed by the Information Management Branch of NASA's Goddard Space Flight Center to manage a large collection of climate-related data of interest to the research community. The PCDS now provides uniform data catalogs, inventories, access methods, graphical displays and statistical calculations for selected NASA and non-NASA data sets. Data manipulation capabilities were developed to permit researchers to easily combine or compare data. The current capabilities of the PCDS include many tools for the statistical survey of climate data. A climate researcher can examine any data set of interest via flexible utilities to create a variety of two- and three-dimensional displays, including vector plots, scatter diagrams, histograms, contour plots, surface diagrams and pseudo-color images. The graphics and statistics subsystems employ an intermediate data storage format which is data-set independent. Outside of the graphics system there exist other utilities to select, filter, list, compress, and calculate time-averages and variances for any data of interest. The PCDS now fully supports approximately twenty different data sets and is being used on a trial basis by several different in-house research grounds.

High quality Gaussian basis sets for fourth-row atoms

NASA Technical Reports Server (NTRS)

Partridge, Harry; Faegri, Knut, Jr.

1992-01-01

Energy optimized Gaussian basis sets of triple-zeta quality for the atoms Rb-Xe have been derived. Two series of basis sets are developed: (24s 16p 10d) and (26s 16p 10d) sets which were expanded to 13d and 19p functions as the 4d and 5p shells become occupied. For the atoms lighter than Cd, the (24s 16p 10d) sets with triple-zeta valence distributions are higher in energy than the corresponding double-zeta distribution. To ensure a triple-zeta distribution and a global energy minimum, the (26s 16p 10d) sets were derived. Total atomic energies from the largest basis sets are between 198 and 284 (mu)E(sub H) above the numerical Hartree-Fock energies.

Effects of the GABA(B) receptor agonist baclofen administered orally on normal food intake and intraperitoneally on fat intake in non-deprived rats.

PubMed

Bains, Rasneer S; Ebenezer, Ivor S

2013-01-05

It has been previously reported that the GABA(B) receptor agonist baclofen decreases food intake after oral administration and fat intake after intraperitoneal administration. The aim of the study was to investigate the effects of baclofen (1-4 mg/ kg) administered orally (Experiment 1) on food intake in non-deprived rats (n=6) and intraperitoneally (Experiment 2) on fat intake in non-deprived rats (n=8) that were naïve to baclofen (1st set of trials) and in the same group of rats after they were sub-chronically exposed to baclofen (2nd set of trials). The results from Experiment 1 show that baclofen had no effects on food intake during the 1st set of trials, but the 2 and 4 mg/kg doses significantly increased food consumption during the 2nd set of trials. Baclofen produced sedation during the 1st set of trials, but tolerance occurred to this effect and was not apparent during the 2nd set of trials. These observations suggest that the motor effects may have competed with the hyperphagic effects of baclofen during the 1st set of trials. The data from Experiment 2 show that baclofen had no effects on fat intake during either the 1st or 2nd set of trials. The results of the study thus indicate that orally administrated baclofen increases food intake and intraperitoneal administration has no effect on fat intake in non-deprived rats under the conditions used in this study. These findings may have important implications for research on the use of baclofen in studies concerned with ingestive behaviours. Copyright © 2012 Elsevier B.V. All rights reserved.

Relativistic well-tempered Gaussian basis sets for helium through mercury

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

Okada, S.; Matsuoka, O.

1989-10-01

Exponent parameters of the nonrelativistically optimized well-tempered Gaussian basis sets of Huzinaga and Klobukowski have been employed for Dirac--Fock--Roothaan calculations without their reoptimization. For light atoms He (atomic number {ital Z}=2)--Rh ({ital Z}=45), the number of exponent parameters used has been the same as the nonrelativistic basis sets and for heavier atoms Pd ({ital Z}=46)--Hg({ital Z}=80), two 2{ital p} (and three 3{ital d}) Gaussian basis functions have been augmented. The scheme of kinetic energy balance and the uniformly charged sphere model of atomic nuclei have been adopted. The qualities of the calculated basis sets are close to the Dirac--Fock limit.

Performance assessment of density functional methods with Gaussian and Slater basis sets using 7σ orbital momentum distributions of N2O

NASA Astrophysics Data System (ADS)

Wang, Feng; Pang, Wenning; Duffy, Patrick

2012-12-01

Performance of a number of commonly used density functional methods in chemistry (B3LYP, Bhandh, BP86, PW91, VWN, LB94, PBe0, SAOP and X3LYP and the Hartree-Fock (HF) method) has been assessed using orbital momentum distributions of the 7σ orbital of nitrous oxide (NNO), which models electron behaviour in a chemically significant region. The density functional methods are combined with a number of Gaussian basis sets (Pople's 6-31G*, 6-311G**, DGauss TZVP and Dunning's aug-cc-pVTZ as well as even-tempered Slater basis sets, namely, et-DZPp, et-QZ3P, et-QZ+5P and et-pVQZ). Orbital momentum distributions of the 7σ orbital in the ground electronic state of NNO, which are obtained from a Fourier transform into momentum space from single point electronic calculations employing the above models, are compared with experimental measurement of the same orbital from electron momentum spectroscopy (EMS). The present study reveals information on performance of (a) the density functional methods, (b) Gaussian and Slater basis sets, (c) combinations of the density functional methods and basis sets, that is, the models, (d) orbital momentum distributions, rather than a group of specific molecular properties and (e) the entire region of chemical significance of the orbital. It is found that discrepancies of this orbital between the measured and the calculated occur in the small momentum region (i.e. large r region). In general, Slater basis sets achieve better overall performance than the Gaussian basis sets. Performance of the Gaussian basis sets varies noticeably when combining with different Vxc functionals, but Dunning's augcc-pVTZ basis set achieves the best performance for the momentum distributions of this orbital. The overall performance of the B3LYP and BP86 models is similar to newer models such as X3LYP and SAOP. The present study also demonstrates that the combinations of the density functional methods and the basis sets indeed make a difference in the quality of the calculated orbitals.

A Comparison of the Behavior of Functional/Basis Set Combinations for Hydrogen-Bonding in the Water Dimer with Emphasis on Basis Set Superposition Error

PubMed Central

Plumley, Joshua A.; Dannenberg, J. J.

2011-01-01

We evaluate the performance of nine functionals (B3LYP, M05, M05-2X, M06, M06-2X, B2PLYP, B2PLYPD, X3LYP, B97D and MPWB1K) in combination with 16 basis sets ranging in complexity from 6-31G(d) to aug-cc-pV5Z for the calculation of the H-bonded water dimer with the goal of defining which combinations of functionals and basis sets provide a combination of economy and accuracy for H-bonded systems. We have compared the results to the best non-DFT molecular orbital calculations and to experimental results. Several of the smaller basis sets lead to qualitatively incorrect geometries when optimized on a normal potential energy surface (PES). This problem disappears when the optimization is performed on a counterpoise corrected PES. The calculated ΔE's with the largest basis sets vary from -4.42 (B97D) to -5.19 (B2PLYPD) kcal/mol for the different functionals. Small basis sets generally predict stronger interactions than the large ones. We found that, due to error compensation, the smaller basis sets gave the best results (in comparison to experimental and high level non-DFT MO calculations) when combined with a functional that predicts a weak interaction with the largest basis set. Since many applications are complex systems and require economical calculations, we suggest the following functional/basis set combinations in order of increasing complexity and cost: 1) D95(d,p) with B3LYP, B97D, M06 or MPWB1k; 2) 6-311G(d,p) with B3LYP; 3) D95++(d,p) with B3LYP, B97D or MPWB1K; 4)6-311++G(d,p) with B3LYP or B97D; and 5) aug-cc-pVDZ with M05-2X, M06-2X or X3LYP. PMID:21328398

A comparison of the behavior of functional/basis set combinations for hydrogen-bonding in the water dimer with emphasis on basis set superposition error.

PubMed

Plumley, Joshua A; Dannenberg, J J

2011-06-01

We evaluate the performance of ten functionals (B3LYP, M05, M05-2X, M06, M06-2X, B2PLYP, B2PLYPD, X3LYP, B97D, and MPWB1K) in combination with 16 basis sets ranging in complexity from 6-31G(d) to aug-cc-pV5Z for the calculation of the H-bonded water dimer with the goal of defining which combinations of functionals and basis sets provide a combination of economy and accuracy for H-bonded systems. We have compared the results to the best non-density functional theory (non-DFT) molecular orbital (MO) calculations and to experimental results. Several of the smaller basis sets lead to qualitatively incorrect geometries when optimized on a normal potential energy surface (PES). This problem disappears when the optimization is performed on a counterpoise (CP) corrected PES. The calculated interaction energies (ΔEs) with the largest basis sets vary from -4.42 (B97D) to -5.19 (B2PLYPD) kcal/mol for the different functionals. Small basis sets generally predict stronger interactions than the large ones. We found that, because of error compensation, the smaller basis sets gave the best results (in comparison to experimental and high-level non-DFT MO calculations) when combined with a functional that predicts a weak interaction with the largest basis set. As many applications are complex systems and require economical calculations, we suggest the following functional/basis set combinations in order of increasing complexity and cost: (1) D95(d,p) with B3LYP, B97D, M06, or MPWB1k; (2) 6-311G(d,p) with B3LYP; (3) D95++(d,p) with B3LYP, B97D, or MPWB1K; (4) 6-311++G(d,p) with B3LYP or B97D; and (5) aug-cc-pVDZ with M05-2X, M06-2X, or X3LYP. Copyright © 2011 Wiley Periodicals, Inc.

Behavior and neural basis of near-optimal visual search

PubMed Central

Ma, Wei Ji; Navalpakkam, Vidhya; Beck, Jeffrey M; van den Berg, Ronald; Pouget, Alexandre

2013-01-01

The ability to search efficiently for a target in a cluttered environment is one of the most remarkable functions of the nervous system. This task is difficult under natural circumstances, as the reliability of sensory information can vary greatly across space and time and is typically a priori unknown to the observer. In contrast, visual-search experiments commonly use stimuli of equal and known reliability. In a target detection task, we randomly assigned high or low reliability to each item on a trial-by-trial basis. An optimal observer would weight the observations by their trial-to-trial reliability and combine them using a specific nonlinear integration rule. We found that humans were near-optimal, regardless of whether distractors were homogeneous or heterogeneous and whether reliability was manipulated through contrast or shape. We present a neural-network implementation of near-optimal visual search based on probabilistic population coding. The network matched human performance. PMID:21552276

On the validity of the basis set superposition error and complete basis set limit extrapolations for the binding energy of the formic acid dimer

NASA Astrophysics Data System (ADS)

Miliordos, Evangelos; Xantheas, Sotiris S.

2015-03-01

We report the variation of the binding energy of the Formic Acid Dimer with the size of the basis set at the Coupled Cluster with iterative Singles, Doubles and perturbatively connected Triple replacements [CCSD(T)] level of theory, estimate the Complete Basis Set (CBS) limit, and examine the validity of the Basis Set Superposition Error (BSSE)-correction for this quantity that was previously challenged by Kalescky, Kraka, and Cremer (KKC) [J. Chem. Phys. 140, 084315 (2014)]. Our results indicate that the BSSE correction, including terms that account for the substantial geometry change of the monomers due to the formation of two strong hydrogen bonds in the dimer, is indeed valid for obtaining accurate estimates for the binding energy of this system as it exhibits the expected decrease with increasing basis set size. We attribute the discrepancy between our current results and those of KKC to their use of a valence basis set in conjunction with the correlation of all electrons (i.e., including the 1s of C and O). We further show that the use of a core-valence set in conjunction with all electron correlation converges faster to the CBS limit as the BSSE correction is less than half than the valence electron/valence basis set case. The uncorrected and BSSE-corrected binding energies were found to produce the same (within 0.1 kcal/mol) CBS limits. We obtain CCSD(T)/CBS best estimates for De = - 16.1 ± 0.1 kcal/mol and for D0 = - 14.3 ± 0.1 kcal/mol, the later in excellent agreement with the experimental value of -14.22 ± 0.12 kcal/mol.

Characterizing and Understanding the Remarkably Slow Basis Set Convergence of Several Minnesota Density Functionals for Intermolecular Interaction Energies

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

Mardirossian, Narbe; Head-Gordon, Martin

2013-08-22

For a set of eight equilibrium intermolecular complexes, it is discovered in this paper that the basis set limit (BSL) cannot be reached by aug-cc-pV5Z for three of the Minnesota density functionals: M06-L, M06-HF, and M11-L. In addition, the M06 and M11 functionals exhibit substantial, but less severe, difficulties in reaching the BSL. By using successively finer grids, it is demonstrated that this issue is not related to the numerical integration of the exchange-correlation functional. In addition, it is shown that the difficulty in reaching the BSL is not a direct consequence of the structure of the augmented functions inmore » Dunning’s basis sets, since modified augmentation yields similar results. By using a very large custom basis set, the BSL appears to be reached for the HF dimer for all of the functionals. As a result, it is concluded that the difficulties faced by several of the Minnesota density functionals are related to an interplay between the form of these functionals and the structure of standard basis sets. It is speculated that the difficulty in reaching the basis set limit is related to the magnitude of the inhomogeneity correction factor (ICF) of the exchange functional. A simple modification of the M06-L exchange functional that systematically reduces the basis set superposition error (BSSE) for the HF dimer in the aug-cc-pVQZ basis set is presented, further supporting the speculation that the difficulty in reaching the BSL is caused by the magnitude of the exchange functional ICF. In conclusion, the BSSE is plotted with respect to the internuclear distance of the neon dimer for two of the examined functionals.« less

Challenges and lessons learned in conducting comparative-effectiveness trials.

PubMed

Herrick, Linda M; Locke, G Richard; Zinsmeister, Alan R; Talley, Nicholas J

2012-05-01

The current health-care environment is demanding evidence-based medicine that relies on clinical trials as the basis for decisions. Clinician investigators are more often finding that they are personally responsible for coordinating large, multisite trials. We present strategies for successful implementation and management of multisite clinical trials and knowledge gained through an international, multisite randomized clinical trial. Topics include team composition, regulatory requirements, study organization and governance, communication strategies, recruitment and retention efforts, budget, technology transfer, and publication.

Challenges and Lessons Learned in Conducting Comparative-Effectiveness Trials

PubMed Central

Herrick, Linda M.; Locke, G. Richard; Zinsmeister, Alan R.; Talley, Nicholas J.

2014-01-01

The current health-care environment is demanding evidence-based medicine that relies on clinical trials as the basis for decisions. Clinician investigators are more often finding that they are personally responsible for coordinating large, multisite trials. We present strategies for successful implementation and management of multisite clinical trials and knowledge gained through an international, multisite randomized clinical trial. Topics include team composition, regulatory requirements, study organization and governance, communication strategies, recruitment and retention efforts, budget, technology transfer, and publication. PMID:22552235

Role of cooperative groups and funding source in clinical trials supporting guidelines for systemic therapy of breast cancer.

PubMed

Tibau, Ariadna; Anguera, Geòrgia; Andrés-Pretel, Fernando; Templeton, Arnoud J; Seruga, Bostjan; Barnadas, Agustí; Amir, Eitan; Ocana, Alberto

2018-03-13

Clinical research is conducted by academia, cooperative groups (CGs) or pharmaceutical industry. Here, we evaluate the role of CGs and funding sources in the development of guidelines for breast cancer therapies. We identified 94 studies. CGs were involved in 28 (30%) studies while industry either partially or fully sponsored 64 (68%) studies. The number of industry funded studies increased over time (from 0% in 1976 to 100% in 2014; p for trend = 0.048). Only 10 (11%) government or academic studies were identified. Studies conducted by GCs included a greater number of subjects (median 448 vs. 284; p = 0.015), were more common in the neo/adjuvant setting ( p < 0.0001), and were more often randomized ( p = 0.018) phase III ( p < 0.0001) trials. Phase III trial remained significant predictor for CG-sponsored trials (OR 7.1 p = 0.004) in a multivariable analysis. Industry funding was associated with higher likelihood of positive outcomes favoring the sponsored experimental arm ( p = 0.013) but this relationship was not seen for CG-sponsored trials ( p = 0.53). ASCO, ESMO, and NCCN guidelines were searched to identify systemic anti-cancer therapies for early-stage and metastatic breast cancer. Trial characteristics and outcomes were collected. We identified sponsors and/or the funding source(s) and determined whether CGs, industry, or government or academic institutions were involved. Chi-square tests were used for comparison between studies. Industry funding is present in the majority of studies providing the basis for which recommendations about treatment of breast cancer are made. Industry funding, but not CG-based funding, was associated with higher likelihood of positive outcomes in clinical studies supporting guidelines for systemic therapy.

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

Miliordos, Evangelos; Aprà, Edoardo; Xantheas, Sotiris S.

We establish a new estimate for the binding energy between two benzene molecules in the parallel-displaced (PD) conformation by systematically converging (i) the intra- and intermolecular geometry at the minimum, (ii) the expansion of the orbital basis set, and (iii) the level of electron correlation. The calculations were performed at the second-order Møller–Plesset perturbation (MP2) and the coupled cluster including singles, doubles, and a perturbative estimate of triples replacement [CCSD(T)] levels of electronic structure theory. At both levels of theory, by including results corrected for basis set superposition error (BSSE), we have estimated the complete basis set (CBS) limit bymore » employing the family of Dunning’s correlation-consistent polarized valence basis sets. The largest MP2 calculation was performed with the cc-pV6Z basis set (2772 basis functions), whereas the largest CCSD(T) calculation was with the cc-pV5Z basis set (1752 basis functions). The cluster geometries were optimized with basis sets up to quadruple-ζ quality, observing that both its intra- and intermolecular parts have practically converged with the triple-ζ quality sets. The use of converged geometries was found to play an important role for obtaining accurate estimates for the CBS limits. Our results demonstrate that the binding energies with the families of the plain (cc-pVnZ) and augmented (aug-cc-pVnZ) sets converge [within <0.01 kcal/mol for MP2 and <0.15 kcal/mol for CCSD(T)] to the same CBS limit. In addition, the average of the uncorrected and BSSE-corrected binding energies was found to converge to the same CBS limit much faster than either of the two constituents (uncorrected or BSSE-corrected binding energies). Due to the fact that the family of augmented basis sets (especially for the larger sets) causes serious linear dependency problems, the plain basis sets (for which no linear dependencies were found) are deemed as a more efficient and straightforward path for obtaining an accurate CBS limit. We considered extrapolations of the uncorrected (ΔE) and BSSE-corrected (ΔE cp) binding energies, their average value (ΔE ave), as well as the average of the latter over the plain and augmented sets (Δ~E ave) with the cardinal number of the basis set n. Our best estimate of the CCSD(T)/CBS limit for the π–π binding energy in the PD benzene dimer is D e = -2.65 ± 0.02 kcal/mol. The best CCSD(T)/cc-pV5Z calculated value is -2.62 kcal/mol, just 0.03 kcal/mol away from the CBS limit. For comparison, the MP2/CBS limit estimate is -5.00 ± 0.01 kcal/mol, demonstrating a 90% overbinding with respect to CCSD(T). Finally, the spin-component-scaled (SCS) MP2 variant was found to closely reproduce the CCSD(T) results for each basis set, while scaled opposite spin (SOS) MP2 yielded results that are too low when compared to CCSD(T).« less

Atomization Energies of SO and SO2; Basis Set Extrapolation Revisted

NASA Technical Reports Server (NTRS)

Bauschlicher, Charles W., Jr.; Ricca, Alessandra; Arnold, James (Technical Monitor)

1998-01-01

The addition of tight functions to sulphur and extrapolation to the complete basis set limit are required to obtain accurate atomization energies. Six different extrapolation procedures are tried. The best atomization energies come from the series of basis sets that yield the most consistent results for all extrapolation techniques. In the variable alpha approach, alpha values larger than 4.5 or smaller than 3, appear to suggest that the extrapolation may not be reliable. It does not appear possible to determine a reliable basis set series using only the triple and quadruple zeta based sets. The scalar relativistic effects reduce the atomization of SO and SO2 by 0.34 and 0.81 kcal/mol, respectively, and clearly must be accounted for if a highly accurate atomization energy is to be computed. The magnitude of the core-valence (CV) contribution to the atomization is affected by missing diffuse valence functions. The CV contribution is much more stable if basis set superposition errors are accounted for. A similar study of SF, SF(+), and SF6 shows that the best family of basis sets varies with the nature of the S bonding.

Calculating Interaction Energies Using First Principle Theories: Consideration of Basis Set Superposition Error and Fragment Relaxation

ERIC Educational Resources Information Center

Bowen, J. Philip; Sorensen, Jennifer B.; Kirschner, Karl N.

2007-01-01

The analysis explains the basis set superposition error (BSSE) and fragment relaxation involved in calculating the interaction energies using various first principle theories. Interacting the correlated fragment and increasing the size of the basis set can help in decreasing the BSSE to a great extent.

Influence of single particle orbital sets and configuration selection on multideterminant wavefunctions in quantum Monte Carlo

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

Clay, Raymond C.; Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, California 94550; Morales, Miguel A., E-mail: moralessilva2@llnl.gov

2015-06-21

Multideterminant wavefunctions, while having a long history in quantum chemistry, are increasingly being used in highly accurate quantum Monte Carlo calculations. Since the accuracy of QMC is ultimately limited by the quality of the trial wavefunction, multi-Slater determinants wavefunctions offer an attractive alternative to Slater-Jastrow and more sophisticated wavefunction ansatz for several reasons. They can be efficiently calculated, straightforwardly optimized, and systematically improved by increasing the number of included determinants. In spite of their potential, however, the convergence properties of multi-Slater determinant wavefunctions with respect to orbital set choice and excited determinant selection are poorly understood, which hinders the applicationmore » of these wavefunctions to large systems and solids. In this paper, by performing QMC calculations on the equilibrium and stretched carbon dimer, we find that convergence of the recovered correlation energy with respect to number of determinants can depend quite strongly on basis set and determinant selection methods, especially where there is strong correlation. We demonstrate that properly chosen orbital sets and determinant selection techniques from quantum chemistry methods can dramatically reduce the required number of determinants (and thus the computational cost) to reach a given accuracy, which we argue shows clear need for an automatic QMC-only method for selecting determinants and generating optimal orbital sets.« less

Design and protocol of the weight loss lottery- a cluster randomized trial.

PubMed

van der Swaluw, Koen; Lambooij, Mattijs S; Mathijssen, Jolanda J P; Schipper, Maarten; Zeelenberg, Marcel; Polder, Johan J; Prast, Henriëtte M

2016-07-01

People often intend to exercise but find it difficult to attend their gyms on a regular basis. At times, people seek and accept deadlines with consequences to realize their own goals (i.e. commitment devices). The aim of our cluster randomized controlled trial is to test whether a lottery-based commitment device can promote regular gym attendance. The winners of the lottery always get feedback on the outcome but can only claim their prize if they attended their gyms on a regular basis. In this paper we present the design and baseline characteristics of a three-arm trial which is performed with 163 overweight participants in six in-company fitness centers in the Netherlands. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation and comparison of predictive individual-level general surrogates.

PubMed

Gabriel, Erin E; Sachs, Michael C; Halloran, M Elizabeth

2018-07-01

An intermediate response measure that accurately predicts efficacy in a new setting at the individual level could be used both for prediction and personalized medical decisions. In this article, we define a predictive individual-level general surrogate (PIGS), which is an individual-level intermediate response that can be used to accurately predict individual efficacy in a new setting. While methods for evaluating trial-level general surrogates, which are predictors of trial-level efficacy, have been developed previously, few, if any, methods have been developed to evaluate individual-level general surrogates, and no methods have formalized the use of cross-validation to quantify the expected prediction error. Our proposed method uses existing methods of individual-level surrogate evaluation within a given clinical trial setting in combination with cross-validation over a set of clinical trials to evaluate surrogate quality and to estimate the absolute prediction error that is expected in a new trial setting when using a PIGS. Simulations show that our method performs well across a variety of scenarios. We use our method to evaluate and to compare candidate individual-level general surrogates over a set of multi-national trials of a pentavalent rotavirus vaccine.

A complex breastfeeding promotion and support intervention in a developing country: study protocol for a randomized clinical trial

PubMed Central

2014-01-01

Background Breastfeeding has countless benefits to mothers, children and community at large, especially in developing countries. Studies from Lebanon report disappointingly low breastfeeding exclusivity and continuation rates. Evidence reveals that antenatal breastfeeding education, professional lactation support, and peer lay support are individually effective at increasing breastfeeding duration and exclusivity, particularly in low-income settings. Given the complex nature of the breastfeeding ecosystem and its barriers in Lebanon, we hypothesize that a complex breastfeeding support intervention, which is centered on the three components mentioned above, would significantly increase breastfeeding rates. Methods/Design A multi-center randomized controlled trial. Study population: 443 healthy pregnant women in their first trimester will be randomized to control or intervention group. Intervention: A “prenatal/postnatal” professional and peer breastfeeding support package continuing till 6 months postpartum, guided by the Social Network and Social Support Theory. Control group will receive standard prenatal and postnatal care. Mothers will be followed up from early pregnancy till five years after delivery. Outcome measures: Total and exclusive breastfeeding rates, quality of life at 1, 3 and 6 months postpartum, maternal breastfeeding knowledge and attitudes at 6 months postpartum, maternal exclusive breastfeeding rates of future infants up to five years from baseline, cost-benefit and cost-effectiveness analyses of the intervention. Statistical analysis: Descriptive and regression analysis will be conducted under the intention to treat basis using the most recent version of SPSS. Discussion Exclusive breastfeeding is a cost-effective public health measure that has a significant impact on infant morbidity and mortality. In a country with limited healthcare resources like Lebanon, developing an effective breastfeeding promotion and support intervention that is easily replicated across various settings becomes a priority. If positive, the results of this study would provide a generalizable model to bolster breastfeeding promotion efforts and contribute to improved child health in Lebanon and the Middle East and North Africa (MENA) region. Trial registration Current Controlled Trials ISRCTN17875591 PMID:24428951

Core Outcomes in Ventilation Trials (COVenT): protocol for a core outcome set using a Delphi survey with a nested randomised trial and observational cohort study.

PubMed

Blackwood, Bronagh; Ringrow, Suzanne; Clarke, Mike; Marshall, John; Rose, Louise; Williamson, Paula; McAuley, Danny

2015-08-20

Among clinical trials of interventions that aim to modify time spent on mechanical ventilation for critically ill patients there is considerable inconsistency in chosen outcomes and how they are measured. The Core Outcomes in Ventilation Trials (COVenT) study aims to develop a set of core outcomes for use in future ventilation trials in mechanically ventilated adults and children. We will use a mixed methods approach that incorporates a randomised trial nested within a Delphi study and a consensus meeting. Additionally, we will conduct an observational cohort study to evaluate uptake of the core outcome set in published studies at 5 and 10 years following core outcome set publication. The three-round online Delphi study will use a list of outcomes that have been reported previously in a review of ventilation trials. The Delphi panel will include a range of stakeholder groups including patient support groups. The panel will be randomised to one of three feedback methods to assess the impact of the feedback mechanism on subsequent ranking of outcomes. A final consensus meeting will be held with stakeholder representatives to review outcomes. The COVenT study aims to develop a core outcome set for ventilation trials in critical care, explore the best Delphi feedback mechanism for achieving consensus and determine if participation increases use of the core outcome set in the long term.

The C-seal trial: colorectal anastomosis protected by a biodegradable drain fixed to the anastomosis by a circular stapler, a multi-center randomized controlled trial

PubMed Central

2012-01-01

Background Anastomotic leakage is a major complication in colorectal surgery and with an incidence of 11% the most common cause of morbidity and mortality. In order to reduce the incidence of anastomotic leakage the C-seal is developed. This intraluminal biodegradable drain is stapled to the anastomosis with a circular stapler and prevents extravasation of intracolonic content in case of an anastomotic dehiscence. The aim of this study is to evaluate the efficacy of the C-seal in reducing anastomotic leakage in stapled colorectal anastomoses, as assessed by anastomotic leakage leading to invasive treatment within 30 days postoperative. Methods The C-seal trial is a prospective multi-center randomized controlled trial with primary endpoint, anastomotic leakage leading to re-intervention within 30 days after operation. In this trial 616 patients will be randomized to the C-seal or control group (1:1), stratified by center, anastomotic height (proximal or distal of peritoneal reflection) and the intention to create a temporary deviating ostomy. Interim analyses are planned after 50% and 75% of patient inclusion. Eligible patients are at least 18 years of age, have any colorectal disease requiring a colorectal anastomosis to be made with a circular stapler in an elective setting, with an ASA-classification < 4. Oral mechanical bowel preparation is mandatory and patients with signs of peritonitis are excluded. The C-seal student team will perform the randomization procedure, supports the operating surgeon during the C-seal application and achieves the monitoring of the trial. Patients are followed for one year after randomization en will be analyzed on an intention to treat basis. Discussion This Randomized Clinical trial is designed to evaluate the effectiveness of the C-seal in preventing clinical anastomotic leakage. Trial registration NTR3080 PMID:23153188

Effectiveness of an annular closure device in a "real-world" population: stratification of registry data using screening criteria from a randomized controlled trial.

PubMed

Kuršumović, Adisa; Rath, Stefan A

2018-01-01

Increased focus has been put on the use of "'real-world" data to support randomized clinical trial (RCT) evidence for clinical decision-making. The objective of this study was to assess the performance of an annular closure device (ACD) after stratifying a consecutive series of "real-world" patients by the screening criteria of an ongoing RCT. This was a single-center registry analysis of 164 subjects who underwent limited discectomy combined with ACD for symptomatic lumbar disc herniation. Patients were stratified into two groups using the selection criteria of a pivotal RCT on the same device: Trial (met inclusion; n=44) or non-Trial (did not meet inclusion; n=120). Patient-reported outcomes, including Oswestry Disability Index (ODI) and visual analog scale (VAS) for leg and back pain, and adverse events were collected from baseline to last follow-up (mean: Trial - 15.6 months; non-Trial - 14.6 months). Statistical analyses were performed with significance set at p <0.05. Patient-reported outcomes were not significantly different between groups at last ( p ≥0.15) and clinical success (≥15-point improvement in ODI score; ≥20-point improvement in VAS scores) was achieved in both the groups. Three non-Trial (2.5%) and three Trial (6.8%) patients experienced symptomatic reherniation ( p =0.34). Rates of reoperation, ACD mesh dislocation/separation, and other radiographic findings were similar between groups ( p =1.00). Outcomes with the ACD appeared advantageous in both the groups, particularly in comparison with historical reherniation rates reported in the same high-risk, large annular defect population. Stratification of this "real-world" series on the basis of RCT screening criteria did not result in significant between-group differences. These findings suggest that the efficacy of the ACD extends beyond the strictly defined patient population being studied in the RCT of this device. Furthermore, reducing the reherniation rate following lumbar discectomy has positive clinical and economic implications.

The effect of diffuse basis functions on valence bond structural weights

NASA Astrophysics Data System (ADS)

Galbraith, John Morrison; James, Andrew M.; Nemes, Coleen T.

2014-03-01

Structural weights and bond dissociation energies have been determined for H-F, H-X, and F-X molecules (-X = -OH, -NH2, and -CH3) at the valence bond self-consistent field (VBSCF) and breathing orbital valence bond (BOVB) levels of theory with the aug-cc-pVDZ and 6-31++G(d,p) basis sets. At the BOVB level, the aug-cc-pVDZ basis set yields a counterintuitive ordering of ionic structural weights when the initial heavy atom s-type basis functions are included. For H-F, H-OH, and F-X, the ordering follows chemical intuition when these basis functions are not included. These counterintuitive weights are shown to be a result of the diffuse polarisation function on one VB fragment being spatially located, in part, on the other VB fragment. Except in the case of F-CH3, this problem is corrected with the 6-31++G(d,p) basis set. The initial heavy atom s-type functions are shown to make an important contribution to the VB orbitals and bond dissociation energies and, therefore, should not be excluded. It is recommended to not use diffuse basis sets in valence bond calculations unless absolutely necessary. If diffuse basis sets are needed, the 6-31++G(d,p) basis set should be used with caution and the structural weights checked against VBSCF values which have been shown to follow the expected ordering in all cases.

Blinded interpretation of study results can feasibly and effectively diminish interpretation bias.

PubMed

Järvinen, Teppo L N; Sihvonen, Raine; Bhandari, Mohit; Sprague, Sheila; Malmivaara, Antti; Paavola, Mika; Schünemann, Holger J; Guyatt, Gordon H

2014-07-01

Controversial and misleading interpretation of data from randomized trials is common. How to avoid misleading interpretation has received little attention. Herein, we describe two applications of an approach that involves blinded interpretation of the results by study investigators. The approach involves developing two interpretations of the results on the basis of a blinded review of the primary outcome data (experimental treatment A compared with control treatment B). One interpretation assumes that A is the experimental intervention and another assumes that A is the control. After agreeing that there will be no further changes, the investigators record their decisions and sign the resulting document. The randomization code is then broken, the correct interpretation chosen, and the manuscript finalized. Review of the document by an external authority before finalization can provide another safeguard against interpretation bias. We found the blinded preparation of a summary of data interpretation described in this article practical, efficient, and useful. Blinded data interpretation may decrease the frequency of misleading data interpretation. Widespread adoption of blinded data interpretation would be greatly facilitated were it added to the minimum set of recommendations outlining proper conduct of randomized controlled trials (eg, the Consolidated Standards of Reporting Trials statement). Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Could CT screening for lung cancer ever be cost effective in the United Kingdom?

PubMed Central

Whynes, David K

2008-01-01

Background The absence of trial evidence makes it impossible to determine whether or not mass screening for lung cancer would be cost effective and, indeed, whether a clinical trial to investigate the problem would be justified. Attempts have been made to resolve this issue by modelling, although the complex models developed to date have required more real-world data than are currently available. Being founded on unsubstantiated assumptions, they have produced estimates with wide confidence intervals and of uncertain relevance to the United Kingdom. Method I develop a simple, deterministic, model of a screening regimen potentially applicable to the UK. The model includes only a limited number of parameters, for the majority of which, values have already been established in non-trial settings. The component costs of screening are derived from government guidance and from published audits, whilst the values for test parameters are derived from clinical studies. The expected health gains as a result of screening are calculated by combining published survival data for screened and unscreened cohorts with data from Life Tables. When a degree of uncertainty over a parameter value exists, I use a conservative estimate, i.e. one likely to make screening appear less, rather than more, cost effective. Results The incremental cost effectiveness ratio of a single screen amongst a high-risk male population is calculated to be around £14,000 per quality-adjusted life year gained. The average cost of this screening regimen per person screened is around £200. It is possible that, when obtained experimentally in any future trial, parameter values will be found to differ from those previously obtained in non-trial settings. On the basis both of differing assumptions about evaluation conventions and of reasoned speculations as to how test parameters and costs might behave under screening, the model generates cost effectiveness ratios as high as around £20,000 and as low as around £7,000. Conclusion It is evident that eventually being able to identify a cost effective regimen of CT screening for lung cancer in the UK is by no means an unreasonable expectation. PMID:18302756

On the effects of basis set truncation and electron correlation in conformers of 2-hydroxy-acetamide

NASA Astrophysics Data System (ADS)

Szarecka, A.; Day, G.; Grout, P. J.; Wilson, S.

Ab initio quantum chemical calculations have been used to study the differences in energy between two gas phase conformers of the 2-hydroxy-acetamide molecule that possess intramolecular hydrogen bonding. In particular, rotation around the central C-C bond has been considered as a factor determining the structure of the hydrogen bond and stabilization of the conformer. Energy calculations include full geometiy optimization using both the restricted matrix Hartree-Fock model and second-order many-body perturbation theory with a number of commonly used basis sets. The basis sets employed ranged from the minimal STO-3G set to [`]split-valence' sets up to 6-31 G. The effects of polarization functions were also studied. The results display a strong basis set dependence.

Achieving Consensus on Total Joint Replacement Trial Outcome Reporting Using the OMERACT Filter: Endorsement of the Final Core Domain Set for Total Hip and Total Knee Replacement Trials for Endstage Arthritis.

PubMed

Singh, Jasvinder A; Dowsey, Michelle M; Dohm, Michael; Goodman, Susan M; Leong, Amye L; Scholte Voshaar, Marieke M J H; Choong, Peter F

2017-11-01

Discussion and endorsement of the OMERACT total joint replacement (TJR) core domain set for total hip replacement (THR) and total knee replacement (TKR) for endstage arthritis; and next steps for selection of instruments. The OMERACT TJR working group met at the 2016 meeting at Whistler, British Columbia, Canada. We summarized the previous systematic reviews, the preliminary OMERACT TJR core domain set and results from previous surveys. We discussed preliminary core domains for TJR clinical trials, made modifications, and identified challenges with domain measurement. Working group participants (n = 26) reviewed, clarified, and endorsed each of the inner and middle circle domains and added a range of motion domain to the research agenda. TJR were limited to THR and TKR but included all endstage hip and knee arthritis refractory to medical treatment. Participants overwhelmingly endorsed identification and evaluation of top instruments mapping to the core domains (100%) and use of subscales of validated multidimensional instruments to measure core domains for the TJR clinical trial core measurement set (92%). An OMERACT core domain set for hip/knee TJR trials has been defined and we are selecting instruments to develop the TJR clinical trial core measurement set to serve as a common foundation for harmonizing measures in TJR clinical trials.

Update on Outcome Measure Development for Large Vessel Vasculitis: Report from OMERACT 12

PubMed Central

Aydin, Sibel Zehra; Direskeneli, Haner; Sreih, Antoine; Alibaz-Oner, Fatma; Gul, Ahmet; Kamali, Sevil; Hatemi, Gulen; Kermani, Tanaz; Mackie, Sarah L.; Mahr, Alfred; Meara, Alexa; Milman, Nataliya; Nugent, Heidi; Robson, Joanna; Tomasson, Gunnar; Merkel, Peter A.

2015-01-01

Objective The rarity of large vessel vasculitis (LVV) is a major factor limiting randomized controlled trials in LVV, resulting in treatment choices in these diseases that are guided mainly by observational studies and expert opinion. Further complicating trials in LVV is the absence of validated and meaningful outcome measures. The Outcome Measures in Rheumatology (OMERACT) vasculitis working group initiated the Large Vessel Vasculitis task force in 2009 to develop data-driven, validated outcome tools for clinical investigation in LVV. This report summarizes the progress that has been made on a disease activity assessment tool and patient-reported outcomes in LVV as well as the group’s research agenda. Methods The OMERACT LVV task force brought an international group of investigators and patient research partners together to work collaboratively on developing outcome tools. The group initially focused on disease activity assessment tools in LVV. Following a systematic literature review, an international Delphi exercise was conducted to obtain expert opinion on principles and domains for disease assessment. The OMERACT vasculitis working group’s LVV task force is also conducting qualitative research with patients, including interviews, focus groups, and engaging patients as research partners, all to ensure that the approach to disease assessment includes measures of patients’ perspectives and that patients have input into the research agenda and process. Results The preliminary results of both the Delphi exercise and the qualitative interviews were discussed at the OMERACT 12 (2014) meeting and the completion of the analyses will produce an initial set of domains and instruments to form the basis of next steps in the research agenda. Conclusion The research agenda continues to evolve, with the ultimate goal of developing an OMERACT-endorsed core set of outcome measures for use in clinical trials of LVV. PMID:26077399

On the optimization of Gaussian basis sets

NASA Astrophysics Data System (ADS)

Petersson, George A.; Zhong, Shijun; Montgomery, John A.; Frisch, Michael J.

2003-01-01

A new procedure for the optimization of the exponents, αj, of Gaussian basis functions, Ylm(ϑ,φ)rle-αjr2, is proposed and evaluated. The direct optimization of the exponents is hindered by the very strong coupling between these nonlinear variational parameters. However, expansion of the logarithms of the exponents in the orthonormal Legendre polynomials, Pk, of the index, j: ln αj=∑k=0kmaxAkPk((2j-2)/(Nprim-1)-1), yields a new set of well-conditioned parameters, Ak, and a complete sequence of well-conditioned exponent optimizations proceeding from the even-tempered basis set (kmax=1) to a fully optimized basis set (kmax=Nprim-1). The error relative to the exact numerical self-consistent field limit for a six-term expansion is consistently no more than 25% larger than the error for the completely optimized basis set. Thus, there is no need to optimize more than six well-conditioned variational parameters, even for the largest sets of Gaussian primitives.

Time to stabilization in single leg drop jump landings: an examination of calculation methods and assessment of differences in sample rate, filter settings and trial length on outcome values.

PubMed

Fransz, Duncan P; Huurnink, Arnold; de Boode, Vosse A; Kingma, Idsart; van Dieën, Jaap H

2015-01-01

Time to stabilization (TTS) is the time it takes for an individual to return to a baseline or stable state following a jump or hop landing. A large variety exists in methods to calculate the TTS. These methods can be described based on four aspects: (1) the input signal used (vertical, anteroposterior, or mediolateral ground reaction force) (2) signal processing (smoothed by sequential averaging, a moving root-mean-square window, or fitting an unbounded third order polynomial), (3) the stable state (threshold), and (4) the definition of when the (processed) signal is considered stable. Furthermore, differences exist with regard to the sample rate, filter settings and trial length. Twenty-five healthy volunteers performed ten 'single leg drop jump landing' trials. For each trial, TTS was calculated according to 18 previously reported methods. Additionally, the effects of sample rate (1000, 500, 200 and 100 samples/s), filter settings (no filter, 40, 15 and 10 Hz), and trial length (20, 14, 10, 7, 5 and 3s) were assessed. The TTS values varied considerably across the calculation methods. The maximum effect of alterations in the processing settings, averaged over calculation methods, were 2.8% (SD 3.3%) for sample rate, 8.8% (SD 7.7%) for filter settings, and 100.5% (SD 100.9%) for trial length. Differences in TTS calculation methods are affected differently by sample rate, filter settings and trial length. The effects of differences in sample rate and filter settings are generally small, while trial length has a large effect on TTS values. Copyright © 2014 Elsevier B.V. All rights reserved.

Local Knowledge and Experiences of Vaccination: Implications for HIV-Preventive Vaccine Trials in South Africa

ERIC Educational Resources Information Center

Lindegger, Graham; Quayle, Michael; Ndlovu, Moses

2007-01-01

This study forms part of the preparation of communities for HIV-preventive vaccine trials in South Africa. On the basis of the assumption that attitudes to any HIV vaccine or vaccine trials will partly be influenced by experiences of vaccination in general, this study aimed to investigate knowledge of, attitudes to, and experiences of vaccination…

Accurate and balanced anisotropic Gaussian type orbital basis sets for atoms in strong magnetic fields.

PubMed

Zhu, Wuming; Trickey, S B

2017-12-28

In high magnetic field calculations, anisotropic Gaussian type orbital (AGTO) basis functions are capable of reconciling the competing demands of the spherically symmetric Coulombic interaction and cylindrical magnetic (B field) confinement. However, the best available a priori procedure for composing highly accurate AGTO sets for atoms in a strong B field [W. Zhu et al., Phys. Rev. A 90, 022504 (2014)] yields very large basis sets. Their size is problematical for use in any calculation with unfavorable computational cost scaling. Here we provide an alternative constructive procedure. It is based upon analysis of the underlying physics of atoms in B fields that allow identification of several principles for the construction of AGTO basis sets. Aided by numerical optimization and parameter fitting, followed by fine tuning of fitting parameters, we devise formulae for generating accurate AGTO basis sets in an arbitrary B field. For the hydrogen iso-electronic sequence, a set depends on B field strength, nuclear charge, and orbital quantum numbers. For multi-electron systems, the basis set formulae also include adjustment to account for orbital occupations. Tests of the new basis sets for atoms H through C (1 ≤ Z ≤ 6) and ions Li + , Be + , and B + , in a wide B field range (0 ≤ B ≤ 2000 a.u.), show an accuracy better than a few μhartree for single-electron systems and a few hundredths to a few mHs for multi-electron atoms. The relative errors are similar for different atoms and ions in a large B field range, from a few to a couple of tens of millionths, thereby confirming rather uniform accuracy across the nuclear charge Z and B field strength values. Residual basis set errors are two to three orders of magnitude smaller than the electronic correlation energies in multi-electron atoms, a signal of the usefulness of the new AGTO basis sets in correlated wavefunction or density functional calculations for atomic and molecular systems in an external strong B field.

Accurate and balanced anisotropic Gaussian type orbital basis sets for atoms in strong magnetic fields

NASA Astrophysics Data System (ADS)

Zhu, Wuming; Trickey, S. B.

2017-12-01

In high magnetic field calculations, anisotropic Gaussian type orbital (AGTO) basis functions are capable of reconciling the competing demands of the spherically symmetric Coulombic interaction and cylindrical magnetic (B field) confinement. However, the best available a priori procedure for composing highly accurate AGTO sets for atoms in a strong B field [W. Zhu et al., Phys. Rev. A 90, 022504 (2014)] yields very large basis sets. Their size is problematical for use in any calculation with unfavorable computational cost scaling. Here we provide an alternative constructive procedure. It is based upon analysis of the underlying physics of atoms in B fields that allow identification of several principles for the construction of AGTO basis sets. Aided by numerical optimization and parameter fitting, followed by fine tuning of fitting parameters, we devise formulae for generating accurate AGTO basis sets in an arbitrary B field. For the hydrogen iso-electronic sequence, a set depends on B field strength, nuclear charge, and orbital quantum numbers. For multi-electron systems, the basis set formulae also include adjustment to account for orbital occupations. Tests of the new basis sets for atoms H through C (1 ≤ Z ≤ 6) and ions Li+, Be+, and B+, in a wide B field range (0 ≤ B ≤ 2000 a.u.), show an accuracy better than a few μhartree for single-electron systems and a few hundredths to a few mHs for multi-electron atoms. The relative errors are similar for different atoms and ions in a large B field range, from a few to a couple of tens of millionths, thereby confirming rather uniform accuracy across the nuclear charge Z and B field strength values. Residual basis set errors are two to three orders of magnitude smaller than the electronic correlation energies in multi-electron atoms, a signal of the usefulness of the new AGTO basis sets in correlated wavefunction or density functional calculations for atomic and molecular systems in an external strong B field.

The application of midbond basis sets in efficient and accurate ab initio calculations on electron-deficient systems

NASA Astrophysics Data System (ADS)

Choi, Chu Hwan

2002-09-01

Ab initio chemistry has shown great promise in reproducing experimental results and in its predictive power. The many complicated computational models and methods seem impenetrable to an inexperienced scientist, and the reliability of the results is not easily interpreted. The application of midbond orbitals is used to determine a general method for use in calculating weak intermolecular interactions, especially those involving electron-deficient systems. Using the criteria of consistency, flexibility, accuracy and efficiency we propose a supermolecular method of calculation using the full counterpoise (CP) method of Boys and Bernardi, coupled with Moller-Plesset (MP) perturbation theory as an efficient electron-correlative method. We also advocate the use of the highly efficient and reliable correlation-consistent polarized valence basis sets of Dunning. To these basis sets, we add a general set of midbond orbitals and demonstrate greatly enhanced efficiency in the calculation. The H2-H2 dimer is taken as a benchmark test case for our method, and details of the computation are elaborated. Our method reproduces with great accuracy the dissociation energies of other previous theoretical studies. The added efficiency of extending the basis sets with conventional means is compared with the performance of our midbond-extended basis sets. The improvement found with midbond functions is notably superior in every case tested. Finally, a novel application of midbond functions to the BH5 complex is presented. The system is an unusual van der Waals complex. The interaction potential curves are presented for several standard basis sets and midbond-enhanced basis sets, as well as for two popular, alternative correlation methods. We report that MP theory appears to be superior to coupled-cluster (CC) in speed, while it is more stable than B3LYP, a widely-used density functional theory (DFT). Application of our general method yields excellent results for the midbond basis sets. Again they prove superior to conventional extended basis sets. Based on these results, we recommend our general approach as a highly efficient, accurate method for calculating weakly interacting systems.

Neural substrates of visuomotor learning based on improved feedback control and prediction

PubMed Central

Grafton, Scott T.; Schmitt, Paul; Horn, John Van; Diedrichsen, Jörn

2008-01-01

Motor skills emerge from learning feedforward commands as well as improvements in feedback control. These two components of learning were investigated in a compensatory visuomotor tracking task on a trial-by-trial basis. Between trial learning was characterized with a state-space model to provide smoothed estimates of feedforward and feedback learning, separable from random fluctuations in motor performance and error. The resultant parameters were correlated with brain activity using magnetic resonance imaging. Learning related to the generation of a feedforward command correlated with activity in dorsal premotor cortex, inferior parietal lobule, supplementary motor area and cingulate motor area, supporting a role of these areas in retrieving and executing a predictive motor command. Modulation of feedback control was associated with activity in bilateral posterior superior parietal lobule as well as right ventral premotor cortex. Performance error correlated with activity in a widespread cortical and subcortical network including bilateral parietal, premotor and rostral anterior cingulate cortex as well as the cerebellar cortex. Finally, trial-by-trial changes of kinematics, as measured by mean absolute hand acceleration, correlated with activity in motor cortex and anterior cerebellum. The results demonstrate that incremental, learning dependent changes can be modeled on a trial-by-trial basis and neural substrates for feedforward control of novel motor programs are localized to secondary motor areas. PMID:18032069

OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of lifestyle diet and exercise interventions for osteoarthritis.

PubMed

Messier, S P; Callahan, L F; Golightly, Y M; Keefe, F J

2015-05-01

The objective was to develop a set of "best practices" for use as a primer for those interested in entering the clinical trials field for lifestyle diet and/or exercise interventions in osteoarthritis (OA), and as a set of recommendations for experienced clinical trials investigators. A subcommittee of the non-pharmacologic therapies committee of the OARSI Clinical Trials Working Group was selected by the Steering Committee to develop a set of recommended principles for non-pharmacologic diet/exercise OA randomized clinical trials. Topics were identified for inclusion by co-authors and reviewed by the subcommittee. Resources included authors' expert opinions, traditional search methods including MEDLINE (via PubMed), and previously published guidelines. Suggested steps and considerations for study methods (e.g., recruitment and enrollment of participants, study design, intervention and assessment methods) were recommended. The recommendations set forth in this paper provide a guide from which a research group can design a lifestyle diet/exercise randomized clinical trial in patients with OA. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Basis set limit and systematic errors in local-orbital based all-electron DFT

NASA Astrophysics Data System (ADS)

Blum, Volker; Behler, Jörg; Gehrke, Ralf; Reuter, Karsten; Scheffler, Matthias

2006-03-01

With the advent of efficient integration schemes,^1,2 numeric atom-centered orbitals (NAO's) are an attractive basis choice in practical density functional theory (DFT) calculations of nanostructured systems (surfaces, clusters, molecules). Though all-electron, the efficiency of practical implementations promises to be on par with the best plane-wave pseudopotential codes, while having a noticeably higher accuracy if required: Minimal-sized effective tight-binding like calculations and chemically accurate all-electron calculations are both possible within the same framework; non-periodic and periodic systems can be treated on equal footing; and the localized nature of the basis allows in principle for O(N)-like scaling. However, converging an observable with respect to the basis set is less straightforward than with competing systematic basis choices (e.g., plane waves). We here investigate the basis set limit of optimized NAO basis sets in all-electron calculations, using as examples small molecules and clusters (N2, Cu2, Cu4, Cu10). meV-level total energy convergence is possible using <=50 basis functions per atom in all cases. We also find a clear correlation between the errors which arise from underconverged basis sets, and the system geometry (interatomic distance). ^1 B. Delley, J. Chem. Phys. 92, 508 (1990), ^2 J.M. Soler et al., J. Phys.: Condens. Matter 14, 2745 (2002).

Basis set construction for molecular electronic structure theory: natural orbital and Gauss-Slater basis for smooth pseudopotentials.

PubMed

Petruzielo, F R; Toulouse, Julien; Umrigar, C J

2011-02-14

A simple yet general method for constructing basis sets for molecular electronic structure calculations is presented. These basis sets consist of atomic natural orbitals from a multiconfigurational self-consistent field calculation supplemented with primitive functions, chosen such that the asymptotics are appropriate for the potential of the system. Primitives are optimized for the homonuclear diatomic molecule to produce a balanced basis set. Two general features that facilitate this basis construction are demonstrated. First, weak coupling exists between the optimal exponents of primitives with different angular momenta. Second, the optimal primitive exponents for a chosen system depend weakly on the particular level of theory employed for optimization. The explicit case considered here is a basis set appropriate for the Burkatzki-Filippi-Dolg pseudopotentials. Since these pseudopotentials are finite at nuclei and have a Coulomb tail, the recently proposed Gauss-Slater functions are the appropriate primitives. Double- and triple-zeta bases are developed for elements hydrogen through argon. These new bases offer significant gains over the corresponding Burkatzki-Filippi-Dolg bases at various levels of theory. Using a Gaussian expansion of the basis functions, these bases can be employed in any electronic structure method. Quantum Monte Carlo provides an added benefit: expansions are unnecessary since the integrals are evaluated numerically.

Auxiliary basis sets for density-fitting second-order Møller-Plesset perturbation theory: weighted core-valence correlation consistent basis sets for the 4d elements Y-Pd.

PubMed

Hill, J Grant

2013-09-30

Auxiliary basis sets (ABS) specifically matched to the cc-pwCVnZ-PP and aug-cc-pwCVnZ-PP orbital basis sets (OBS) have been developed and optimized for the 4d elements Y-Pd at the second-order Møller-Plesset perturbation theory level. Calculation of the core-valence electron correlation energies for small to medium sized transition metal complexes demonstrates that the error due to the use of these new sets in density fitting is three to four orders of magnitude smaller than that due to the OBS incompleteness, and hence is considered negligible. Utilizing the ABSs in the resolution-of-the-identity component of explicitly correlated calculations is also investigated, where it is shown that i-type functions are important to produce well-controlled errors in both integrals and correlation energy. Benchmarking at the explicitly correlated coupled cluster with single, double, and perturbative triple excitations level indicates impressive convergence with respect to basis set size for the spectroscopic constants of 4d monofluorides; explicitly correlated double-ζ calculations produce results close to conventional quadruple-ζ, and triple-ζ is within chemical accuracy of the complete basis set limit. Copyright © 2013 Wiley Periodicals, Inc.

Adaptive local basis set for Kohn–Sham density functional theory in a discontinuous Galerkin framework II: Force, vibration, and molecular dynamics calculations

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

Zhang, Gaigong; Lin, Lin, E-mail: linlin@math.berkeley.edu; Computational Research Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720

Recently, we have proposed the adaptive local basis set for electronic structure calculations based on Kohn–Sham density functional theory in a pseudopotential framework. The adaptive local basis set is efficient and systematically improvable for total energy calculations. In this paper, we present the calculation of atomic forces, which can be used for a range of applications such as geometry optimization and molecular dynamics simulation. We demonstrate that, under mild assumptions, the computation of atomic forces can scale nearly linearly with the number of atoms in the system using the adaptive local basis set. We quantify the accuracy of the Hellmann–Feynmanmore » forces for a range of physical systems, benchmarked against converged planewave calculations, and find that the adaptive local basis set is efficient for both force and energy calculations, requiring at most a few tens of basis functions per atom to attain accuracies required in practice. Since the adaptive local basis set has implicit dependence on atomic positions, Pulay forces are in general nonzero. However, we find that the Pulay force is numerically small and systematically decreasing with increasing basis completeness, so that the Hellmann–Feynman force is sufficient for basis sizes of a few tens of basis functions per atom. We verify the accuracy of the computed forces in static calculations of quasi-1D and 3D disordered Si systems, vibration calculation of a quasi-1D Si system, and molecular dynamics calculations of H{sub 2} and liquid Al–Si alloy systems, where we show systematic convergence to benchmark planewave results and results from the literature.« less

Adaptive local basis set for Kohn–Sham density functional theory in a discontinuous Galerkin framework II: Force, vibration, and molecular dynamics calculations

DOE PAGES

Zhang, Gaigong; Lin, Lin; Hu, Wei; ...

2017-01-27

Recently, we have proposed the adaptive local basis set for electronic structure calculations based on Kohn–Sham density functional theory in a pseudopotential framework. The adaptive local basis set is efficient and systematically improvable for total energy calculations. In this paper, we present the calculation of atomic forces, which can be used for a range of applications such as geometry optimization and molecular dynamics simulation. We demonstrate that, under mild assumptions, the computation of atomic forces can scale nearly linearly with the number of atoms in the system using the adaptive local basis set. We quantify the accuracy of the Hellmann–Feynmanmore » forces for a range of physical systems, benchmarked against converged planewave calculations, and find that the adaptive local basis set is efficient for both force and energy calculations, requiring at most a few tens of basis functions per atom to attain accuracies required in practice. Sin ce the adaptive local basis set has implicit dependence on atomic positions, Pulay forces are in general nonzero. However, we find that the Pulay force is numerically small and systematically decreasing with increasing basis completeness, so that the Hellmann–Feynman force is sufficient for basis sizes of a few tens of basis functions per atom. We verify the accuracy of the computed forces in static calculations of quasi-1D and 3D disordered Si systems, vibration calculation of a quasi-1D Si system, and molecular dynamics calculations of H 2 and liquid Al–Si alloy systems, where we show systematic convergence to benchmark planewave results and results from the literature.« less

Adaptive local basis set for Kohn–Sham density functional theory in a discontinuous Galerkin framework II: Force, vibration, and molecular dynamics calculations

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

Zhang, Gaigong; Lin, Lin; Hu, Wei

Recently, we have proposed the adaptive local basis set for electronic structure calculations based on Kohn–Sham density functional theory in a pseudopotential framework. The adaptive local basis set is efficient and systematically improvable for total energy calculations. In this paper, we present the calculation of atomic forces, which can be used for a range of applications such as geometry optimization and molecular dynamics simulation. We demonstrate that, under mild assumptions, the computation of atomic forces can scale nearly linearly with the number of atoms in the system using the adaptive local basis set. We quantify the accuracy of the Hellmann–Feynmanmore » forces for a range of physical systems, benchmarked against converged planewave calculations, and find that the adaptive local basis set is efficient for both force and energy calculations, requiring at most a few tens of basis functions per atom to attain accuracies required in practice. Sin ce the adaptive local basis set has implicit dependence on atomic positions, Pulay forces are in general nonzero. However, we find that the Pulay force is numerically small and systematically decreasing with increasing basis completeness, so that the Hellmann–Feynman force is sufficient for basis sizes of a few tens of basis functions per atom. We verify the accuracy of the computed forces in static calculations of quasi-1D and 3D disordered Si systems, vibration calculation of a quasi-1D Si system, and molecular dynamics calculations of H 2 and liquid Al–Si alloy systems, where we show systematic convergence to benchmark planewave results and results from the literature.« less

Adaptive local basis set for Kohn-Sham density functional theory in a discontinuous Galerkin framework II: Force, vibration, and molecular dynamics calculations

NASA Astrophysics Data System (ADS)

Zhang, Gaigong; Lin, Lin; Hu, Wei; Yang, Chao; Pask, John E.

2017-04-01

Recently, we have proposed the adaptive local basis set for electronic structure calculations based on Kohn-Sham density functional theory in a pseudopotential framework. The adaptive local basis set is efficient and systematically improvable for total energy calculations. In this paper, we present the calculation of atomic forces, which can be used for a range of applications such as geometry optimization and molecular dynamics simulation. We demonstrate that, under mild assumptions, the computation of atomic forces can scale nearly linearly with the number of atoms in the system using the adaptive local basis set. We quantify the accuracy of the Hellmann-Feynman forces for a range of physical systems, benchmarked against converged planewave calculations, and find that the adaptive local basis set is efficient for both force and energy calculations, requiring at most a few tens of basis functions per atom to attain accuracies required in practice. Since the adaptive local basis set has implicit dependence on atomic positions, Pulay forces are in general nonzero. However, we find that the Pulay force is numerically small and systematically decreasing with increasing basis completeness, so that the Hellmann-Feynman force is sufficient for basis sizes of a few tens of basis functions per atom. We verify the accuracy of the computed forces in static calculations of quasi-1D and 3D disordered Si systems, vibration calculation of a quasi-1D Si system, and molecular dynamics calculations of H2 and liquid Al-Si alloy systems, where we show systematic convergence to benchmark planewave results and results from the literature.

A randomised trial of high and low pressure level settings on an adjustable ventriculoperitoneal shunt valve for idiopathic normal pressure hydrocephalus: results of the Dutch evaluation programme Strata shunt (DEPSS) trial.

PubMed

Delwel, Ernst J; de Jong, Dirk A; Dammers, Ruben; Kurt, Erkan; van den Brink, Wimar; Dirven, Clemens M F

2013-07-01

In treating idiopathic normal pressure hydrocephalus (INPH) with a shunt there is always a risk of underdrainage or overdrainage. The hypothesis is tested whether patients treated using an adjustable valve preset at the highest opening pressure leads to comparable good clinical results with less subdural effusions than in a control group with an opening pressure preset at a low pressure level. A multicentre prospective randomised trial was performed on a total of 58 patients suspected of INPH. Thirty patients were assigned to (control) group 1 and received a Strata shunt (Medtronic, Goleta, USA) with the valve preset at a performance level (PL) of 1.0, while 28 patients were assigned to group 2 and received a Strata shunt with the valve preset at PL 2.5. In this group the PL was allowed to be lowered until improvement or radiological signs of overdrainage were met. Significantly more subdural effusions were observed in the improved patients of group 1. There was no statistically significant difference in improvement between both groups overall. On the basis of this multicentre prospective randomised trial it is to be recommended to treat patients with INPH with a shunt with an adjustable valve, preset at the highest opening pressure and lowered until clinical improvement or radiological signs of overdrainage occur although slower improvement and more shunt adjustments might be the consequence.

Benchmark of Ab Initio Bethe-Salpeter Equation Approach with Numeric Atom-Centered Orbitals

NASA Astrophysics Data System (ADS)

Liu, Chi; Kloppenburg, Jan; Kanai, Yosuke; Blum, Volker

The Bethe-Salpeter equation (BSE) approach based on the GW approximation has been shown to be successful for optical spectra prediction of solids and recently also for small molecules. We here present an all-electron implementation of the BSE using numeric atom-centered orbital (NAO) basis sets. In this work, we present benchmark of BSE implemented in FHI-aims for low-lying excitation energies for a set of small organic molecules, the well-known Thiel's set. The difference between our implementation (using an analytic continuation of the GW self-energy on the real axis) and the results generated by a fully frequency dependent GW treatment on the real axis is on the order of 0.07 eV for the benchmark molecular set. We study the convergence behavior to the complete basis set limit for excitation spectra, using a group of valence correlation consistent NAO basis sets (NAO-VCC-nZ), as well as for standard NAO basis sets for ground state DFT with extended augmentation functions (NAO+aug). The BSE results and convergence behavior are compared to linear-response time-dependent DFT, where excellent numerical convergence is shown for NAO+aug basis sets.

Kinetic balance and variational bounds failure in the solution of the Dirac equation in a finite Gaussian basis set

NASA Technical Reports Server (NTRS)

Dyall, Kenneth G.; Faegri, Knut, Jr.

1990-01-01

The paper investigates bounds failure in calculations using Gaussian basis sets for the solution of the one-electron Dirac equation for the 2p1/2 state of Hg(79+). It is shown that bounds failure indicates inadequacies in the basis set, both in terms of the exponent range and the number of functions. It is also shown that overrepresentation of the small component space may lead to unphysical results. It is concluded that it is important to use matched large and small component basis sets with an adequate size and exponent range.

Ab Initio and Analytic Intermolecular Potentials for Ar-CF₄

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

Vayner, Grigoriy; Alexeev, Yuri; Wang, Jiangping

2006-03-09

Ab initio calculations at the CCSD(T) level of theory are performed to characterize the Ar + CF ₄ intermolecular potential. Extensive calculations, with and without a correction for basis set superposition error (BSSE), are performed with the cc-pVTZ basis set. Additional calculations are performed with other correlation consistent (cc) basis sets to extrapolate the Ar---CF₄potential energy minimum to the complete basis set (CBS) limit. Both the size of the basis set and BSSE have substantial effects on the Ar + CF₄ potential. Calculations with the cc-pVTZ basis set and without a BSSE correction, appear to give a good representation ofmore » the potential at the CBS limit and with a BSSE correction. In addition, MP2 theory is found to give potential energies in very good agreement with those determined by the much higher level CCSD(T) theory. Two analytic potential energy functions were determined for Ar + CF₄by fitting the cc-pVTZ calculations both with and without a BSSE correction. These analytic functions were written as a sum of two body potentials and excellent fits to the ab initio potentials were obtained by representing each two body interaction as a Buckingham potential.« less

On the performance of large Gaussian basis sets for the computation of total atomization energies

NASA Technical Reports Server (NTRS)

Martin, J. M. L.

1992-01-01

The total atomization energies of a number of molecules have been computed using an augmented coupled-cluster method and (5s4p3d2f1g) and 4s3p2d1f) atomic natural orbital (ANO) basis sets, as well as the correlation consistent valence triple zeta plus polarization (cc-pVTZ) correlation consistent valence quadrupole zeta plus polarization (cc-pVQZ) basis sets. The performance of ANO and correlation consistent basis sets is comparable throughout, although the latter can result in significant CPU time savings. Whereas the inclusion of g functions has significant effects on the computed Sigma D(e) values, chemical accuracy is still not reached for molecules involving multiple bonds. A Gaussian-1 (G) type correction lowers the error, but not much beyond the accuracy of the G1 model itself. Using separate corrections for sigma bonds, pi bonds, and valence pairs brings down the mean absolute error to less than 1 kcal/mol for the spdf basis sets, and about 0.5 kcal/mol for the spdfg basis sets. Some conclusions on the success of the Gaussian-1 and Gaussian-2 models are drawn.

Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials

PubMed Central

Gilbert, Peter B.; Juraska, Michal; deCamp, Allan C.; Karuna, Shelly; Edupuganti, Srilatha; Mgodi, Nyaradzo; Donnell, Deborah J.; Bentley, Carter; Sista, Nirupama; Andrew, Philip; Isaacs, Abby; Huang, Yunda; Zhang, Lily; Capparelli, Edmund; Kochar, Nidhi; Wang, Jing; Eshleman, Susan H.; Mayer, Kenneth H.; Magaret, Craig A.; Hural, John; Kublin, James G.; Gray, Glenda; Montefiori, David C.; Gomez, Margarita M.; Burns, David N.; McElrath, Julie; Ledgerwood, Julie; Graham, Barney S.; Mascola, John R.; Cohen, Myron; Corey, Lawrence

2017-01-01

Background Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been developed as potential agents for prevention of HIV-1 infection. The HIV Vaccine Trials Network and the HIV Prevention Trials Network are conducting the Antibody Mediated Prevention (AMP) trials to assess whether, and how, intravenous infusion of the anti-CD4 binding site bnAb, VRC01, prevents HIV-1 infection. These are the first test-of-concept studies to assess HIV-1 bnAb prevention efficacy in humans. Methods The AMP trials are two parallel phase 2b HIV-1 prevention efficacy trials conducted in two cohorts: 2700 HIV-uninfected men and transgender persons who have sex with men in the United States, Peru, Brazil, and Switzerland; and 1500 HIV-uninfected sexually active women in seven countries in sub-Saharan Africa. Participants are randomized 1:1:1 to receive an intravenous infusion of 10 mg/kg VRC01, 30 mg/kg VRC01, or a control preparation every 8 weeks for a total of 10 infusions. Each trial is designed (1) to assess overall prevention efficacy (PE) pooled over the two VRC01 dose groups vs. control and (2) to assess VRC01 dose and laboratory markers as correlates of protection (CoPs) against overall and genotype- and phenotype-specific infection. Results Each AMP trial is designed to have 90% power to detect PE > 0% if PE is ≥ 60%. The AMP trials are also designed to identify VRC01 properties (i.e., concentration and effector functions) that correlate with protection and to provide insight into mechanistic CoPs. CoPs are assessed using data from breakthrough HIV-1 infections, including genetic sequences and sensitivities to VRC01-mediated neutralization and Fc effector functions. Conclusions The AMP trials test whether VRC01 can prevent HIV-1 infection in two study populations. If affirmative, they will provide information for estimating the optimal dosage of VRC01 (or subsequent derivatives) and identify threshold levels of neutralization and Fc effector functions associated with high-level protection, setting a benchmark for future vaccine evaluation and constituting a bridge to other bnAb approaches for HIV-1 prevention. PMID:29218117

Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials.

PubMed

Gilbert, Peter B; Juraska, Michal; deCamp, Allan C; Karuna, Shelly; Edupuganti, Srilatha; Mgodi, Nyaradzo; Donnell, Deborah J; Bentley, Carter; Sista, Nirupama; Andrew, Philip; Isaacs, Abby; Huang, Yunda; Zhang, Lily; Capparelli, Edmund; Kochar, Nidhi; Wang, Jing; Eshleman, Susan H; Mayer, Kenneth H; Magaret, Craig A; Hural, John; Kublin, James G; Gray, Glenda; Montefiori, David C; Gomez, Margarita M; Burns, David N; McElrath, Julie; Ledgerwood, Julie; Graham, Barney S; Mascola, John R; Cohen, Myron; Corey, Lawrence

2017-01-01

Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been developed as potential agents for prevention of HIV-1 infection. The HIV Vaccine Trials Network and the HIV Prevention Trials Network are conducting the Antibody Mediated Prevention (AMP) trials to assess whether, and how, intravenous infusion of the anti-CD4 binding site bnAb, VRC01, prevents HIV-1 infection. These are the first test-of-concept studies to assess HIV-1 bnAb prevention efficacy in humans. The AMP trials are two parallel phase 2b HIV-1 prevention efficacy trials conducted in two cohorts: 2700 HIV-uninfected men and transgender persons who have sex with men in the United States, Peru, Brazil, and Switzerland; and 1500 HIV-uninfected sexually active women in seven countries in sub-Saharan Africa. Participants are randomized 1:1:1 to receive an intravenous infusion of 10 mg/kg VRC01, 30 mg/kg VRC01, or a control preparation every 8 weeks for a total of 10 infusions. Each trial is designed (1) to assess overall prevention efficacy (PE) pooled over the two VRC01 dose groups vs. control and (2) to assess VRC01 dose and laboratory markers as correlates of protection (CoPs) against overall and genotype- and phenotype-specific infection. Each AMP trial is designed to have 90% power to detect PE > 0% if PE is ≥ 60%. The AMP trials are also designed to identify VRC01 properties (i.e., concentration and effector functions) that correlate with protection and to provide insight into mechanistic CoPs. CoPs are assessed using data from breakthrough HIV-1 infections, including genetic sequences and sensitivities to VRC01-mediated neutralization and Fc effector functions. The AMP trials test whether VRC01 can prevent HIV-1 infection in two study populations. If affirmative, they will provide information for estimating the optimal dosage of VRC01 (or subsequent derivatives) and identify threshold levels of neutralization and Fc effector functions associated with high-level protection, setting a benchmark for future vaccine evaluation and constituting a bridge to other bnAb approaches for HIV-1 prevention.

Standard requirements for GCP-compliant data management in multinational clinical trials.

PubMed

Ohmann, Christian; Kuchinke, Wolfgang; Canham, Steve; Lauritsen, Jens; Salas, Nader; Schade-Brittinger, Carmen; Wittenberg, Michael; McPherson, Gladys; McCourt, John; Gueyffier, Francois; Lorimer, Andrea; Torres, Ferràn

2011-03-22

A recent survey has shown that data management in clinical trials performed by academic trial units still faces many difficulties (e.g. heterogeneity of software products, deficits in quality management, limited human and financial resources and the complexity of running a local computer centre). Unfortunately, no specific, practical and open standard for both GCP-compliant data management and the underlying IT-infrastructure is available to improve the situation. For that reason the "Working Group on Data Centres" of the European Clinical Research Infrastructures Network (ECRIN) has developed a standard specifying the requirements for high quality GCP-compliant data management in multinational clinical trials. International, European and national regulations and guidelines relevant to GCP, data security and IT infrastructures, as well as ECRIN documents produced previously, were evaluated to provide a starting point for the development of standard requirements. The requirements were produced by expert consensus of the ECRIN Working group on Data Centres, using a structured and standardised process. The requirements were divided into two main parts: an IT part covering standards for the underlying IT infrastructure and computer systems in general, and a Data Management (DM) part covering requirements for data management applications in clinical trials. The standard developed includes 115 IT requirements, split into 15 separate sections, 107 DM requirements (in 12 sections) and 13 other requirements (2 sections). Sections IT01 to IT05 deal with the basic IT infrastructure while IT06 and IT07 cover validation and local software development. IT08 to IT015 concern the aspects of IT systems that directly support clinical trial management. Sections DM01 to DM03 cover the implementation of a specific clinical data management application, i.e. for a specific trial, whilst DM04 to DM12 address the data management of trials across the unit. Section IN01 is dedicated to international aspects and ST01 to the competence of a trials unit's staff. The standard is intended to provide an open and widely used set of requirements for GCP-compliant data management, particularly in academic trial units. It is the intention that ECRIN will use these requirements as the basis for the certification of ECRIN data centres.

Bridging the gap between evidence-based innovation and national health-sector reform in Ghana.

PubMed

Awoonor-Williams, John Koku; Feinglass, Ellie S; Tobey, Rachel; Vaughan-Smith, Maya N; Nyonator, Frank K; Jones, Tanya C

2004-09-01

Although experimental trials often identify optimal strategies for improving community health, transferring operational innovation from well-funded research programs to resource-constrained settings often languishes. Because research initiatives are based in institutions equipped with unique resources and staff capabilities, results are often dismissed by decisionmakers as irrelevant to large-scale operations and national health policy. This article describes an initiative undertaken in Nkwanta District, Ghana, focusing on this problem. The Nkwanta District initiative is a critical link between the experimental study conducted in Navrongo, Ghana, and a national effort to scale up the innovations developed in that study. A 2002 Nkwanta district-level survey provides the basis for assessing the likelihood that the Navrongo model is replicable elsewhere in Ghana. The effect of community-based health planning and services exposure on family planning and safe-motherhood indicators supports the hypothesis that Navrongo effects are transferable to impoverished rural settings elsewhere, confirming the need for strategies to bridge the gap between Navrongo evidence-based innovation and national health-sector reform.

[Trial manufacture of subsidiary tool and use of technique for shoulder joint of "Scapula Y"].

PubMed

Maejima, Hideyuki; Okamoto, Takahide; Yamazaki, Norihito; Hiyoshi, Kan; Tanaka, Tamotsu; Mori, Takeshi; Ako, Toshitaka; Ogawa, Norihisa

2002-07-01

The technique of "Scapula Y " is effective for capturing forward/backward dislocation of the humeral head and variation in surgical spine fracture. It is also indispensable for describing images of ossification at the tendon plate of the lower lobe of the acrominon and impingement syndrome. However, owing to large individual variations in body shape and position and shape of the scapula, the conventional method does not lend itself to stable reproduction of position or provide adequate diagnostic information. We measured the central angle of entry from scapula m24 pairs of dried bone (Indian) into the spine of the scapula from horizontal and forehead planes to determine the range of variation together with the clinical data referred to in the next paragraph. We then manufactured a trial subsidiary tool to set the angle of the central entering beam base on the acrominon to the spine of the scapula using data on measured angle from 50 clinical radiographs. We identified improvement in radiography of the scapula by using the subsidiary tool designed and manufactured on the basis of the above measured data.

Brains creating stories of selves: the neural basis of autobiographical reasoning

PubMed Central

Cassol, Helena; Phillips, Christophe; Balteau, Evelyne; Salmon, Eric; Van der Linden, Martial

2014-01-01

Personal identity critically depends on the creation of stories about the self and one’s life. The present study investigates the neural substrates of autobiographical reasoning, a process central to the construction of such narratives. During functional magnetic resonance imaging scanning, participants approached a set of personally significant memories in two different ways: in some trials, they remembered the concrete content of the events (autobiographical remembering), whereas in other trials they reflected on the broader meaning and implications of their memories (autobiographical reasoning). Relative to remembering, autobiographical reasoning recruited a left-lateralized network involved in conceptual processing [including the dorsal medial prefrontal cortex (MPFC), inferior frontal gyrus, middle temporal gyrus and angular gyrus]. The ventral MPFC—an area that may function to generate personal/affective meaning—was not consistently engaged during autobiographical reasoning across participants but, interestingly, the activity of this region was modulated by individual differences in interest and willingness to engage in self-reflection. These findings support the notion that autobiographical reasoning and the construction of personal narratives go beyond mere remembering in that they require deriving meaning and value from past experiences. PMID:23482628

Distinct brain networks for adaptive and stable task control in humans

PubMed Central

Dosenbach, Nico U. F.; Fair, Damien A.; Miezin, Francis M.; Cohen, Alexander L.; Wenger, Kristin K.; Dosenbach, Ronny A. T.; Fox, Michael D.; Snyder, Abraham Z.; Vincent, Justin L.; Raichle, Marcus E.; Schlaggar, Bradley L.; Petersen, Steven E.

2007-01-01

Control regions in the brain are thought to provide signals that configure the brain's moment-to-moment information processing. Previously, we identified regions that carried signals related to task-control initiation, maintenance, and adjustment. Here we characterize the interactions of these regions by applying graph theory to resting state functional connectivity MRI data. In contrast to previous, more unitary models of control, this approach suggests the presence of two distinct task-control networks. A frontoparietal network included the dorsolateral prefrontal cortex and intraparietal sulcus. This network emphasized start-cue and error-related activity and may initiate and adapt control on a trial-by-trial basis. The second network included dorsal anterior cingulate/medial superior frontal cortex, anterior insula/frontal operculum, and anterior prefrontal cortex. Among other signals, these regions showed activity sustained across the entire task epoch, suggesting that this network may control goal-directed behavior through the stable maintenance of task sets. These two independent networks appear to operate on different time scales and affect downstream processing via dissociable mechanisms. PMID:17576922

Practice-based evidence study design for comparative effectiveness research.

PubMed

Horn, Susan D; Gassaway, Julie

2007-10-01

To describe a new, rigorous, comprehensive practice-based evidence for clinical practice improvement (PBE-CPI) study methodology, and compare its features, advantages, and disadvantages to those of randomized controlled trials and sophisticated statistical methods for comparative effectiveness research. PBE-CPI incorporates natural variation within data from routine clinical practice to determine what works, for whom, when, and at what cost. It uses the knowledge of front-line caregivers, who develop study questions and define variables as part of a transdisciplinary team. Its comprehensive measurement framework provides a basis for analyses of significant bivariate and multivariate associations between treatments and outcomes, controlling for patient differences, such as severity of illness. PBE-CPI studies can uncover better practices more quickly than randomized controlled trials or sophisticated statistical methods, while achieving many of the same advantages. We present examples of actionable findings from PBE-CPI studies in postacute care settings related to comparative effectiveness of medications, nutritional support approaches, incontinence products, physical therapy activities, and other services. Outcomes improved when practices associated with better outcomes in PBE-CPI analyses were adopted in practice.

ANIMAL MANURES AS FEEDSTUFFS: CATTLE MANURE FEEDING TRIALS

EPA Science Inventory

The utilization of 'as-collected' and processed beef cattle and dairy cow manure, manure screenings and anaerobically digested cattle manures was evaluated on the basis of the results of feeding trials reported in the literature. The maximum level of incorporating these manures i...

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

Shirkov, Leonid; Makarewicz, Jan, E-mail: jama@amu.edu.pl

An ab initio intermolecular potential energy surface (PES) has been constructed for the benzene-krypton (BKr) van der Waals (vdW) complex. The interaction energy has been calculated at the coupled cluster level of theory with single, double, and perturbatively included triple excitations using different basis sets. As a result, a few analytical PESs of the complex have been determined. They allowed a prediction of the complex structure and its vibrational vdW states. The vibrational energy level pattern exhibits a distinct polyad structure. Comparison of the equilibrium structure, the dipole moment, and vibrational levels of BKr with their experimental counterparts has allowedmore » us to design an optimal basis set composed of a small Dunning’s basis set for the benzene monomer, a larger effective core potential adapted basis set for Kr and additional midbond functions. Such a basis set yields vibrational energy levels that agree very well with the experimental ones as well as with those calculated from the available empirical PES derived from the microwave spectra of the BKr complex. The basis proposed can be applied to larger complexes including Kr because of a reasonable computational cost and accurate results.« less

Polarized atomic orbitals for self-consistent field electronic structure calculations

NASA Astrophysics Data System (ADS)

Lee, Michael S.; Head-Gordon, Martin

1997-12-01

We present a new self-consistent field approach which, given a large "secondary" basis set of atomic orbitals, variationally optimizes molecular orbitals in terms of a small "primary" basis set of distorted atomic orbitals, which are simultaneously optimized. If the primary basis is taken as a minimal basis, the resulting functions are termed polarized atomic orbitals (PAO's) because they are valence (or core) atomic orbitals which have distorted or polarized in an optimal way for their molecular environment. The PAO's derive their flexibility from the fact that they are formed from atom-centered linear-combinations of the larger set of secondary atomic orbitals. The variational conditions satisfied by PAO's are defined, and an iterative method for performing a PAO-SCF calculation is introduced. We compare the PAO-SCF approach against full SCF calculations for the energies, dipoles, and molecular geometries of various molecules. The PAO's are potentially useful for studying large systems that are currently intractable with larger than minimal basis sets, as well as offering potential interpretative benefits relative to calculations in extended basis sets.

The Ethics of Randomized Controlled Trials in Social Settings: Can Social Trials Be Scientifically Promising and Must There Be Equipoise?

ERIC Educational Resources Information Center

Fives, Allyn; Russell, Daniel W.; Canavan, John; Lyons, Rena; Eaton, Patricia; Devaney, Carmel; Kearns, Norean; O'Brien, Aoife

2015-01-01

In a randomized controlled trial (RCT), treatments are assigned randomly and treatments are withheld from participants. Is it ethically permissible to conduct an RCT in a social setting? This paper addresses two conditions for justifying RCTs: that there should be a state of equipoise and that the trial should be scientifically promising.…

Neural substrates of approach-avoidance conflict decision-making

PubMed Central

Aupperle, Robin L.; Melrose, Andrew J.; Francisco, Alex; Paulus, Martin P.; Stein, Murray B.

2014-01-01

Animal approach-avoidance conflict paradigms have been used extensively to operationalize anxiety, quantify the effects of anxiolytic agents, and probe the neural basis of fear and anxiety. Results from human neuroimaging studies support that a frontal-striatal-amygdala neural circuitry is important for approach-avoidance learning. However, the neural basis of decision-making is much less clear in this context. Thus, we combined a recently developed human approach-avoidance paradigm with functional magnetic resonance imaging (fMRI) to identify neural substrates underlying approach-avoidance conflict decision-making. Fifteen healthy adults completed the approach-avoidance conflict (AAC) paradigm during fMRI. Analyses of variance were used to compare conflict to non-conflict (avoid-threat and approach-reward) conditions and to compare level of reward points offered during the decision phase. Trial-by-trial amplitude modulation analyses were used to delineate brain areas underlying decision-making in the context of approach/avoidance behavior. Conflict trials as compared to the non-conflict trials elicited greater activation within bilateral anterior cingulate cortex (ACC), anterior insula, and caudate, as well as right dorsolateral prefrontal cortex. Right caudate and lateral PFC activation was modulated by level of reward offered. Individuals who showed greater caudate activation exhibited less approach behavior. On a trial-by-trial basis, greater right lateral PFC activation related to less approach behavior. Taken together, results suggest that the degree of activation within prefrontal-striatal-insula circuitry determines the degree of approach versus avoidance decision-making. Moreover, the degree of caudate and lateral PFC activation is related to individual differences in approach-avoidance decision-making. Therefore, the AAC paradigm is ideally suited to probe anxiety-related processing differences during approach-avoidance decision-making. PMID:25224633

Neural substrates of approach-avoidance conflict decision-making.

PubMed

Aupperle, Robin L; Melrose, Andrew J; Francisco, Alex; Paulus, Martin P; Stein, Murray B

2015-02-01

Animal approach-avoidance conflict paradigms have been used extensively to operationalize anxiety, quantify the effects of anxiolytic agents, and probe the neural basis of fear and anxiety. Results from human neuroimaging studies support that a frontal-striatal-amygdala neural circuitry is important for approach-avoidance learning. However, the neural basis of decision-making is much less clear in this context. Thus, we combined a recently developed human approach-avoidance paradigm with functional magnetic resonance imaging (fMRI) to identify neural substrates underlying approach-avoidance conflict decision-making. Fifteen healthy adults completed the approach-avoidance conflict (AAC) paradigm during fMRI. Analyses of variance were used to compare conflict to nonconflict (avoid-threat and approach-reward) conditions and to compare level of reward points offered during the decision phase. Trial-by-trial amplitude modulation analyses were used to delineate brain areas underlying decision-making in the context of approach/avoidance behavior. Conflict trials as compared to the nonconflict trials elicited greater activation within bilateral anterior cingulate cortex, anterior insula, and caudate, as well as right dorsolateral prefrontal cortex (PFC). Right caudate and lateral PFC activation was modulated by level of reward offered. Individuals who showed greater caudate activation exhibited less approach behavior. On a trial-by-trial basis, greater right lateral PFC activation related to less approach behavior. Taken together, results suggest that the degree of activation within prefrontal-striatal-insula circuitry determines the degree of approach versus avoidance decision-making. Moreover, the degree of caudate and lateral PFC activation related to individual differences in approach-avoidance decision-making. Therefore, the approach-avoidance conflict paradigm is ideally suited to probe anxiety-related processing differences during approach-avoidance decision-making. © 2014 Wiley Periodicals, Inc.

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.

The CONSENSUS study: protocol for a mixed methods study to establish which outcomes should be included in a core outcome set for oropharyngeal cancer

PubMed Central

2014-01-01

Background The incidence of oropharyngeal cancer is increasing in the developed world. This has led to a large rise in research activity and clinical trials in this area, yet there is no consensus on which outcomes should be measured. As a result, the outcomes measured often differ between trials of comparable interventions, making the combination or comparison of results between trials impossible. Outcomes may also be ‘cherry-picked’, such that favourable results are reported, and less favourable results withheld. The development of a minimum outcome reporting standard, known as a core outcome set, goes some way to addressing these problems. Core outcome sets are ideally developed using a patient-centred approach so that the outcomes measured are relevant to patients and clinical practice. Core outcome sets drive up the quality and relevance of research by ensuring that the right outcomes are consistently measured and reported in trials in specific areas of health or healthcare. Methods/Design This is a mixed methods study involving three phases to develop a core outcome set for oropharyngeal cancer clinical trials. Firstly, a systematic review will establish which outcomes are measured in published oropharyngeal cancer randomised controlled trials (RCTs). Secondly, qualitative interviews with patients and carers in the UK and the USA will aim to establish which outcomes are important to these stakeholders. Data from these first two stages will be used to develop a comprehensive list of outcomes to be considered for inclusion in the core outcome set. In the third stage, patients and clinicians will participate in an iterative consensus exercise known as a Delphi study to refine the contents of the core outcome set. This protocol lays out the methodology to be implemented in the CONSENSUS study. Discussion A core outcome set defines a minimum outcome reporting standard for clinical trials in a particular area of health or healthcare. Its consistent implementation in oropharyngeal cancer clinical trials will improve the quality and relevance of research. Trials and registration This study is registered at the National Institute for Health Research (NIHR) Clinical Research Network (CRN) portfolio, ID 13823 (17 January 2013). PMID:24885068

Online Early Resilience Intervention for Combat-Related PTSD in Military Primary Healthcare Settings: A Randomized Trial of DESTRESS-PC

DTIC Science & Technology

2009-08-01

Bryant, R, Engel, CC (2004). A therapist-assisted internet self-help program for traumatic stress . Professional Psychology: Research and Practice, 35...Combat-Related PTSD in Military Primary Healthcare Settings: A Randomized Trial of “DESTRESS-PC” PRINCIPAL INVESTIGATOR: Charles Engel...Early Resilience Intervention for Combat-Related PTSD in Military Primary Healthcare Settings: A Randomized Trial of DESTRESS-PC 5b. GRANT NUMBER

Design and baseline characteristics of the 10 Small Steps Study: a randomised controlled trial of an intervention to promote healthy behaviour using a lifestyle score and personalised feedback.

PubMed

Parekh, Sanjoti; Vandelanotte, Corneel; King, David; Boyle, Frances M

2012-03-12

Non-communicable diseases (NCDs) are the leading causes of death globally and are associated with a limited set of common, modifiable health behaviours: tobacco use, physical inactivity, harmful use of alcohol and unhealthy diet. General practice offers an ideal avenue for addressing such health behaviours on a population-wide basis. This paper describes the protocol of a multiple health behaviour change intervention designed for implementation in general practice and summarises the baseline characteristics of its participants. The 10 Small Steps (10SS) study, a randomised controlled trial, involved 4,678 adult general practice patients in Queensland, Australia. Self-reported data were collected to establish the proportion of participants meeting recommended guidelines for ten health behaviours: physical activity, body mass index, alcohol, smoking and six dietary behaviours. Participants were randomised to four groups: contact at baseline only ('single intervention' and corresponding control group) and contact at baseline and 3 months ('dual intervention' and corresponding control group). At each contact the participants received a computer-tailored feedback and one page information sheet according to their allocation to intervention or control groups. Change in the intervention group compared to the control group was assessed at 3 and12 months after baseline data collection.Responses were summed to calculate an individual lifestyle score (the Prudence Score), which ranged from 0 to 10. The baseline response was 56.5% (4678 of 8343 invited participants) and the study sample was primarily female (68.7%) with an average age of 47 years. The mean Prudence Score was 5.8 (95%CI 5.75-5.85). Baseline data from the 10SS study show that nearly all participants engage in some health behaviours but relatively few adhere simultaneously to a core set of dietary and lifestyle behaviours associated with risk of NCDs. Ample scope exists to improve health behaviour to reduce NCDs in the general practice setting and the 10SS study trial will provide data on the extent to which a minimal computer-tailored intervention can meet this objective. The protocol developed for the 10SS study has potential for translation into routine general practice as it has minimal impact on practice routine whilst contributing to primary prevention objectives. The Australian New Zealand Clinical Trials Registry ACTRN12611001213932.

42 CFR 415.170 - Conditions for payment on a fee schedule basis for physician services in a teaching setting.

Code of Federal Regulations, 2010 CFR

2010-10-01

... physician services in a teaching setting. 415.170 Section 415.170 Public Health CENTERS FOR MEDICARE... BY PHYSICIANS IN PROVIDERS, SUPERVISING PHYSICIANS IN TEACHING SETTINGS, AND RESIDENTS IN CERTAIN SETTINGS Physician Services in Teaching Settings § 415.170 Conditions for payment on a fee schedule basis...

Projected Hybrid Orbitals: A General QM/MM Method

PubMed Central

2015-01-01

A projected hybrid orbital (PHO) method was described to model the covalent boundary in a hybrid quantum mechanical and molecular mechanical (QM/MM) system. The PHO approach can be used in ab initio wave function theory and in density functional theory with any basis set without introducing system-dependent parameters. In this method, a secondary basis set on the boundary atom is introduced to formulate a set of hybrid atomic orbtials. The primary basis set on the boundary atom used for the QM subsystem is projected onto the secondary basis to yield a representation that provides a good approximation to the electron-withdrawing power of the primary basis set to balance electronic interactions between QM and MM subsystems. The PHO method has been tested on a range of molecules and properties. Comparison with results obtained from QM calculations on the entire system shows that the present PHO method is a robust and balanced QM/MM scheme that preserves the structural and electronic properties of the QM region. PMID:25317748

A novel Gaussian-Sinc mixed basis set for electronic structure calculations

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

Jerke, Jonathan L.; Lee, Young; Tymczak, C. J.

2015-08-14

A Gaussian-Sinc basis set methodology is presented for the calculation of the electronic structure of atoms and molecules at the Hartree–Fock level of theory. This methodology has several advantages over previous methods. The all-electron electronic structure in a Gaussian-Sinc mixed basis spans both the “localized” and “delocalized” regions. A basis set for each region is combined to make a new basis methodology—a lattice of orthonormal sinc functions is used to represent the “delocalized” regions and the atom-centered Gaussian functions are used to represent the “localized” regions to any desired accuracy. For this mixed basis, all the Coulomb integrals are definablemore » and can be computed in a dimensional separated methodology. Additionally, the Sinc basis is translationally invariant, which allows for the Coulomb singularity to be placed anywhere including on lattice sites. Finally, boundary conditions are always satisfied with this basis. To demonstrate the utility of this method, we calculated the ground state Hartree–Fock energies for atoms up to neon, the diatomic systems H{sub 2}, O{sub 2}, and N{sub 2}, and the multi-atom system benzene. Together, it is shown that the Gaussian-Sinc mixed basis set is a flexible and accurate method for solving the electronic structure of atomic and molecular species.« less

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

Hill, J. Grant, E-mail: grant.hill@sheffield.ac.uk, E-mail: kipeters@wsu.edu; Peterson, Kirk A., E-mail: grant.hill@sheffield.ac.uk, E-mail: kipeters@wsu.edu

New correlation consistent basis sets, cc-pVnZ-PP-F12 (n = D, T, Q), for all the post-d main group elements Ga–Rn have been optimized for use in explicitly correlated F12 calculations. The new sets, which include not only orbital basis sets but also the matching auxiliary sets required for density fitting both conventional and F12 integrals, are designed for correlation of valence sp, as well as the outer-core d electrons. The basis sets are constructed for use with the previously published small-core relativistic pseudopotentials of the Stuttgart-Cologne variety. Benchmark explicitly correlated coupled-cluster singles and doubles with perturbative triples [CCSD(T)-F12b] calculations of themore » spectroscopic properties of numerous diatomic molecules involving 4p, 5p, and 6p elements have been carried out and compared to the analogous conventional CCSD(T) results. In general the F12 results obtained with a n-zeta F12 basis set were comparable to conventional aug-cc-pVxZ-PP or aug-cc-pwCVxZ-PP basis set calculations obtained with x = n + 1 or even x = n + 2. The new sets used in CCSD(T)-F12b calculations are particularly efficient at accurately recovering the large correlation effects of the outer-core d electrons.« less

The categorical structure of semantic memory for famous people: a new approach using release from proactive interference.

PubMed

Darling, Stephen; Valentine, Tim

2005-05-01

Memory for familiar people is essential to understand their identity and guide social interaction. Nevertheless, we know surprisingly little about the structure of such memory. Previous research has assumed that semantic memory for people has a categorical structure, but recently it was proposed that memory for people consists only of associations and lacks any categorical structure. Four experiments are reported that use a novel approach by adapting the 'release from proactive interference' (RPI) methodology for use with lists of famous names. Proactive interference occurs when items presented on successive trials are drawn from the same category. Recall can improve following a change to a different category. Sets of names were selected relating to aspects previously demonstrated, on the basis of reaction time data, to form a category (occupation) and a property (nationality) of celebrities (Johnston & Bruce, 1990). RPI was observed for a change at both levels of representation but was only present without explicitly cueing the change of set when the stimuli differed at the category level. At the property level, RPI was only evident when change of set was explicitly cued. RPI was absent at the set change in a novel, ad hoc distinction suggesting that the effect reflected the underlying memory structure.

Marketing depression care management to employers: design of a randomized controlled trial.

PubMed

Rost, Kathryn M; Marshall, Donna

2010-03-16

Randomized trials demonstrate that depression care management can improve clinical and work outcomes sufficiently for selected employers to realize a return on investment. Employers can now purchase depression products that provide depression care management, defined as employee screening, education, monitoring, and clinician feedback for all depressed employees. We developed an intervention to encourage employers to purchase a depression product that offers the type, intensity, and duration of care management shown to improve clinical and work outcomes. In a randomized controlled trial conducted with 360 employers of 30 regional business coalitions, the research team proposes to compare the impact of a value-based marketing intervention to usual-care marketing on employer purchase of depression products. The study will also identify mediators and organizational-level moderators of intervention impact. Employers randomized to the value-based condition receive a presentation encouraging them to purchase depression products scientifically shown to benefit the employee and the employer. Employers randomized to the usual-care condition receive a presentation encouraging them to monitor and improve quality indicators for outpatient depression treatment. Because previous research demonstrates that the usual-care intervention will have little to no impact on employer purchasing, depression product purchasing rates in the usual-care condition capture vendor efforts to market depression products to employers in both conditions while the value-based intervention is being conducted. Employers in both conditions are also provided free technical assistance to undertake the actions each presentation encourages. The research team will use intent-to-treat models of all available data to evaluate intervention impact on the purchase of depression products using a cumulative incidence analysis of 12- and 24-month data. By addressing the 'value to whom?' question, the study advances knowledge about one of the most pivotal problems in the translation of evidence-based care to 'real world' settings: whether purchasers can be influenced to buy healthcare products on the basis of value and not exclusively on the basis of cost. If value-based marketing increases depression product purchase rates over usual care, this study will provide encouragement to market new healthcare products on the basis of the product's value to the purchaser as well as the recipient of care. NCT01013220.

Overview, hurdles, and future work in adaptive designs: perspectives from a National Institutes of Health-funded workshop.

PubMed

Coffey, Christopher S; Levin, Bruce; Clark, Christina; Timmerman, Cate; Wittes, Janet; Gilbert, Peter; Harris, Sara

2012-12-01

The clinical trials community has a never-ending search for dependable and reliable ways to improve clinical research. This exploration has led to considerable interest in adaptive clinical trial designs, which provide the flexibility to adjust trial characteristics on the basis of data reviewed at interim stages. Statisticians and clinical investigators have proposed or implemented a wide variety of adaptations in clinical trials, but specific approaches have met with differing levels of support. Within industry, investigators are actively exploring the benefits and pitfalls associated with adaptive designs (ADs). For example, a Drug Information Association (DIA) working group on ADs has engaged regulatory agencies in discussions. Many researchers working on publicly funded clinical trials, however, are not yet fully engaged in this discussion. We organized the Scientific Advances in Adaptive Clinical Trial Designs Workshop to begin a conversation about using ADs in publicly funded research. Held in November of 2009, the 1½-day workshop brought together representatives from the National Institutes of Health (NIH), the Food and Drug Administration (FDA), the European Medicines Agency (EMA), the pharmaceutical industry, nonprofit foundations, the patient advocacy community, and academia. The workshop offered a forum for participants to address issues of ADs that arise at the planning, designing, and execution stages of clinical trials, and to hear the perspectives of influential members of the clinical trials community. The participants also set forth recommendations for guiding action to promote the appropriate use of ADs. These recommendations have since been presented, discussed, and vetted in a number of venues including the University of Pennsylvania Conference on Statistical Issues in Clinical Trials and the Society for Clinical Trials annual meeting. To provide a brief overview of ADs, describe the rationale behind conducting the workshop, and summarize the main recommendations that were produced as a result of this workshop. There is a growing interest in the use of adaptive clinical trial designs. However, a number of logistical barriers need to be addressed in order to obtain the potential advantages of an AD. Currently, the pharmaceutical industry is well ahead of academic trialists with respect to addressing these barriers. Academic trialists will need to address important issues such as education, infrastructure, modifications to existing funding models, and the impact on Data and Safety Monitoring Boards (DSMB) in order to achieve the possible benefits of adaptive clinical trial designs.

A Cluster-Randomized Controlled Trial of a Simplified Multifaceted Management Program for Individuals at High Cardiovascular Risk (SimCard Trial) in Rural Tibet, China and Haryana, India

PubMed Central

Tian, Maoyi; Ajay, Vamadevan S.; Dunzhu, Danzeng; Hameed, Safraj S.; Li, Xian; Liu, Zhong; Li, Cong; Chen, Hao; Cho, KaWing; Li, Ruilai; Zhao, Xingshan; Jindal, Devraj; Rawal, Ishita; Ali, Mohammed K.; Peterson, Eric D.; Ji, Jiachao; Amarchand, Ritvik; Krishnan, Anand; Tandon, Nikhil; Xu, Li-Qun; Wu, Yangfeng; Prabhakaran, Dorairaj; Yan, Lijing L.

2015-01-01

Background In rural areas in China and India, cardiovascular disease burden is high but economic and healthcare resources are limited. This study aims to develop and evaluate a simplified cardiovascular management program (SimCard) delivered by community health workers (CHWs) with the aid of a smartphone-based electronic decision support system. Methods and Results The SimCard study was a yearlong cluster-randomized controlled trial conducted in 47 villages (27 in China and 20 in India). 2,086 ‘high cardiovascular risk’ individuals (aged 40 years or older with self-reported history of coronary heart disease, stroke, diabetes, and/or measured systolic blood pressure ≥160 mmHg) were recruited. Participants in the intervention villages were managed by CHWs through an Android-powered “app” on a monthly basis focusing on two medication use and two lifestyle modifications. Compared with the control group, the intervention group had a 25.5% (P<0.001) higher net increase in the primary outcome of the proportion of patient-reported anti-hypertensive medication use pre-and-post intervention. There were also significant differences in certain secondary outcomes: aspirin use (net difference 17.1%, P<0.001) and systolic blood pressure (−2.7 mmHg, P=0.04). However, no significant changes were observed in the lifestyle factors. The intervention was culturally tailored and country-specific results revealed important differences between the regions. Conclusions The results indicate that the simplified cardiovascular management program improved quality of primary care and clinical outcomes in resource-poor settings in China and India. Larger trials in more places are needed to ascertain potential impacts on mortality and morbidity outcomes. Clinical Trial Registration Information clinicaltrials.gov. Identifier: NCT01503814. PMID:26187183

Aripiprazole Lauroxil Compared with Paliperidone Palmitate in Patients with Schizophrenia: An Indirect Treatment Comparison.

PubMed

Cameron, Chris; Zummo, Jacqueline; Desai, Dharmik N; Drake, Christine; Hutton, Brian; Kotb, Ahmed; Weiden, Peter J

Aripiprazole lauroxil (AL) is a long-acting injectable atypical antipsychotic recently approved for treatment of schizophrenia on the basis of a large-scale trial of two doses of AL versus placebo. There are no direct-comparison studies with paliperidone palmitate (PP; long-acting antipsychotic used most often in acute settings) for the acute psychotic episode. To indirectly compare efficacy and safety of the pivotal AL study with all PP studies meeting indirect comparison criteria. Systematic searches of MEDLINE, Embase, Cochrane CENTRAL, PsycINFO, ClinicalTrials.gov, International Clinical Trials Registry Platform, and gray literature were performed to identify randomized controlled trials of PP with similar designs to the AL trial. Bayesian network meta-analysis compared treatments with respect to symptom response and tolerability issues including weight gain, akathisia, parkinsonism, and likelihood of treatment-emergent adverse events. Three appropriate PP studies were identified for indirect comparison. Both doses of AL (441 mg and 882 mg monthly) were used and compared with two efficacious doses of PP (156 mg and 234 mg monthly). All four active-treatment conditions were associated with comparable reductions in acute symptoms (Positive and Negative Syndrome Scale) versus placebo and were of similar magnitude (range of mean difference -8.12 to -12.01, with overlapping 95% credible intervals). Between-group comparisons of active-treatment arms were associated with summary estimates of magnitude near 0. No clinically meaningful differences in selected safety or tolerability parameter incidence were found between active treatments. These results suggest that both AL and PP are effective for treatment of adults experiencing acute exacerbation of schizophrenia. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Network analysis of the genomic basis of the placebo effect

PubMed Central

Wang, Rui-Sheng; Hall, Kathryn T.; Giulianini, Franco; Passow, Dani; Kaptchuk, Ted J.

2017-01-01

The placebo effect is a phenomenon in which patients who are given an inactive treatment (e.g., inert pill) show a perceived or actual improvement in a medical condition. Placebo effects in clinical trials have been investigated for many years especially because placebo treatments often serve as the control arm of randomized clinical trial designs. Recent observations suggest that placebo effects may be modified by genetics. This observation has given rise to the term “placebome,” which refers to a group of genome-related mediators that affect an individual’s response to placebo treatments. In this study, we conduct a network analysis of the placebome and identify a placebome module in the comprehensive human interactome using a seed-connector algorithm. The placebome module is significantly enriched with neurotransmitter signaling pathways and brain-specific proteins. We validate the placebome module using a large cohort of the Women’s Genome Health Study (WGHS) trial and demonstrate that the placebome module is significantly enriched with genes whose SNPs modify the outcome in the placebo arm of the trial. To gain insights into placebo effects in different diseases and drug treatments, we use a network proximity measure to examine the closeness of the placebome module to different disease modules and drug target modules. The results demonstrate that the network proximity of the placebome module to disease modules in the interactome significantly correlates with the strength of the placebo effect in the corresponding diseases. The proximity of the placebome module to molecular pathways affected by certain drug classes indicates the existence of placebo-drug interactions. This study is helpful for understanding the molecular mechanisms mediating the placebo response, and sets the stage for minimizing its effects in clinical trials and for developing therapeutic strategies that intentionally engage it. PMID:28570268

Comparison of fMRI analysis methods for heterogeneous BOLD responses in block design studies

PubMed Central

Bernal-Casas, David; Fang, Zhongnan; Lee, Jin Hyung

2017-01-01

A large number of fMRI studies have shown that the temporal dynamics of evoked BOLD responses can be highly heterogeneous. Failing to model heterogeneous responses in statistical analysis can lead to significant errors in signal detection and characterization and alter the neurobiological interpretation. However, to date it is not clear that, out of a large number of options, which methods are robust against variability in the temporal dynamics of BOLD responses in block-design studies. Here, we used rodent optogenetic fMRI data with heterogeneous BOLD responses and simulations guided by experimental data as a means to investigate different analysis methods’ performance against heterogeneous BOLD responses. Evaluations are carried out within the general linear model (GLM) framework and consist of standard basis sets as well as independent component analysis (ICA). Analyses show that, in the presence of heterogeneous BOLD responses, conventionally used GLM with a canonical basis set leads to considerable errors in the detection and characterization of BOLD responses. Our results suggest that the 3rd and 4th order gamma basis sets, the 7th to 9th order finite impulse response (FIR) basis sets, the 5th to 9th order B-spline basis sets, and the 2nd to 5th order Fourier basis sets are optimal for good balance between detection and characterization, while the 1st order Fourier basis set (coherence analysis) used in our earlier studies show good detection capability. ICA has mostly good detection and characterization capabilities, but detects a large volume of spurious activation with the control fMRI data. PMID:27993672

[Methodological quality evaluation of randomized controlled trials for traditional Chinese medicines for treatment of sub-health].

PubMed

Zhao, Jun; Liao, Xing; Zhao, Hui; Li, Zhi-Geng; Wang, Nan-Yue; Wang, Li-Min

2016-11-01

To evaluate the methodological quality of the randomized controlled trials(RCTs) for traditional Chinese medicines for treatment of sub-health, in order to provide a scientific basis for the improvement of clinical trials and systematic review. Such databases as CNKI, CBM, VIP, Wanfang, EMbase, Medline, Clinical Trials, Web of Science and Cochrane Library were searched for RCTS for traditional Chinese medicines for treatment of sub-health between the time of establishment and February 29, 2016. Cochrane Handbook 5.1 was used to screen literatures and extract data, and CONSORT statement and CONSORT for traditional Chinese medicine statement were adopted as the basis for quality evaluation. Among the 72 RCTs included in this study, 67 (93.05%) trials described the inter-group baseline data comparability, 39(54.17%) trials described the unified diagnostic criteria, 28(38.89%) trials described the unified standards of efficacy, 4 (5.55%) trials mentioned the multi-center study, 19(26.38%) trials disclosed the random distribution method, 6(8.33%) trials used the random distribution concealment, 15(20.83%) trials adopted the method of blindness, 3(4.17%) study reported the sample size estimation in details, 5 (6.94%) trials showed a sample size of more than two hundred, 19(26.38%) trials reported the number of withdrawal, defluxion cases and those lost to follow-up, but only 2 trials adopted the ITT analysis,10(13.89%) trials reported the follow-up results, none of the trial reported the test registration and the test protocol, 48(66.7%) trials reported all of the indicators of expected outcomes, 26(36.11%) trials reported the adverse reactions and adverse events, and 4(5.56%) trials reported patient compliance. The overall quality of these randomized controlled trials for traditional Chinese medicines for treatment of sub-health is low, with methodological defects in different degrees. Therefore, it is still necessary to emphasize the correct application of principles such as blindness, randomization and control in RCTs, while requiring reporting in accordance with international standards. Copyright© by the Chinese Pharmaceutical Association.

Conventional and Explicitly Correlated ab Initio Benchmark Study on Water Clusters: Revision of the BEGDB and WATER27 Data Sets.

PubMed

Manna, Debashree; Kesharwani, Manoj K; Sylvetsky, Nitai; Martin, Jan M L

2017-07-11

Benchmark ab initio energies for BEGDB and WATER27 data sets have been re-examined at the MP2 and CCSD(T) levels with both conventional and explicitly correlated (F12) approaches. The basis set convergence of both conventional and explicitly correlated methods has been investigated in detail, both with and without counterpoise corrections. For the MP2 and CCSD-MP2 contributions, rapid basis set convergence observed with explicitly correlated methods is compared to conventional methods. However, conventional, orbital-based calculations are preferred for the calculation of the (T) term, since it does not benefit from F12. CCSD(F12*) converges somewhat faster with the basis set than CCSD-F12b for the CCSD-MP2 term. The performance of various DFT methods is also evaluated for the BEGDB data set, and results show that Head-Gordon's ωB97X-V and ωB97M-V functionals outperform all other DFT functionals. Counterpoise-corrected DSD-PBEP86 and raw DSD-PBEPBE-NL also perform well and are close to MP2 results. In the WATER27 data set, the anionic (deprotonated) water clusters exhibit unacceptably slow basis set convergence with the regular cc-pVnZ-F12 basis sets, which have only diffuse s and p functions. To overcome this, we have constructed modified basis sets, denoted aug-cc-pVnZ-F12 or aVnZ-F12, which have been augmented with diffuse functions on the higher angular momenta. The calculated final dissociation energies of BEGDB and WATER27 data sets are available in the Supporting Information. Our best calculated dissociation energies can be reproduced through n-body expansion, provided one pushes to the basis set and electron correlation limit for the two-body term; for the three-body term, post-MP2 contributions (particularly CCSD-MP2) are important for capturing the three-body dispersion effects. Terms beyond four-body can be adequately captured at the MP2-F12 level.

Neoadjuvant chemotherapy regimens in treatment of breast cancer: a systematic review and network meta-analysis protocol.

PubMed

Pathak, Mona; Dwivedi, Sada Nand; Deo, S V S; Thakur, Bhaskar; Sreenivas, Vishnubhatla; Rath, G K

2018-06-26

Neoadjuvant chemotherapy (NACT), a standard of care for locally advanced breast cancer patients, is widely used for early breast cancer patients also. The varying role of regimens used as NACT needs to be investigated. Despite availability of some randomized controlled trials (RCTs), it is unclear which treatment regimen suits best. Further, there is no study comparing all the three regimens. Accordingly, present study will compare the efficacy of anthracyclines, taxanes, and targeted therapy administered in neoadjuvant setting on the basis of oncological outcomes and functional outcomes. Online databases PubMed and Cochrane Register of Controlled Trials will be searched to acquire eligible studies. Further, content of relevant journals, references of relevant articles, and proceedings of major related conference will also be searched. The RCTs comparing any of abovementioned regimen as NACT on breast cancer patients will be eligible. Two reviewers independently and in duplicate will screen the records on the basis of title and abstract and complete full-text review to determine eligibility. Similarly, data extraction and risk of bias assessment will be done by two independent reviewers. The pair-wise meta-analysis as well as network meta-analysis will be conducted to assess the relative efficacy of anthracyclines, taxanes, and targeted therapy regimens. The present systematic review will improve the understanding of the relative efficacies of the three treatment regimens and possibly guide the clinical practices by providing the current best evidence on the efficacy of various regimens of NACT in the management of breast cancer patients. PROSPERO ( CRD42016027236 ).

A Meshless Method Using Radial Basis Functions for Beam Bending Problems

NASA Technical Reports Server (NTRS)

Raju, I. S.; Phillips, D. R.; Krishnamurthy, T.

2004-01-01

A meshless local Petrov-Galerkin (MLPG) method that uses radial basis functions (RBFs) as trial functions in the study of Euler-Bernoulli beam problems is presented. RBFs, rather than generalized moving least squares (GMLS) interpolations, are used to develop the trial functions. This choice yields a computationally simpler method as fewer matrix inversions and multiplications are required than when GMLS interpolations are used. Test functions are chosen as simple weight functions as they are in the conventional MLPG method. Compactly and noncompactly supported RBFs are considered. Noncompactly supported cubic RBFs are found to be preferable. Patch tests, mixed boundary value problems, and problems with complex loading conditions are considered. Results obtained from the radial basis MLPG method are either of comparable or better accuracy than those obtained when using the conventional MLPG method.

On the Use of a Mixed Gaussian/Finite-Element Basis Set for the Calculation of Rydberg States

NASA Technical Reports Server (NTRS)

Thuemmel, Helmar T.; Langhoff, Stephen (Technical Monitor)

1996-01-01

Configuration-interaction studies are reported for the Rydberg states of the helium atom using mixed Gaussian/finite-element (GTO/FE) one particle basis sets. Standard Gaussian valence basis sets are employed, like those, used extensively in quantum chemistry calculations. It is shown that the term values for high-lying Rydberg states of the helium atom can be obtained accurately (within 1 cm -1), even for a small GTO set, by augmenting the n-particle space with configurations, where orthonormalized interpolation polynomials are singly occupied.

Attention-based image similarity measure with application to content-based information retrieval

NASA Astrophysics Data System (ADS)

Stentiford, Fred W. M.

2003-01-01

Whilst storage and capture technologies are able to cope with huge numbers of images, image retrieval is in danger of rendering many repositories valueless because of the difficulty of access. This paper proposes a similarity measure that imposes only very weak assumptions on the nature of the features used in the recognition process. This approach does not make use of a pre-defined set of feature measurements which are extracted from a query image and used to match those from database images, but instead generates features on a trial and error basis during the calculation of the similarity measure. This has the significant advantage that features that determine similarity can match whatever image property is important in a particular region whether it be a shape, a texture, a colour or a combination of all three. It means that effort is expended searching for the best feature for the region rather than expecting that a fixed feature set will perform optimally over the whole area of an image and over every image in a database. The similarity measure is evaluated on a problem of distinguishing similar shapes in sets of black and white symbols.

Recent progress in relapsed multiple myeloma therapy: implications for treatment decisions.

PubMed

Moreau, Philippe; de Wit, Edwin

2017-10-01

The availability of novel therapies for the treatment of multiple myeloma has had a dramatic impact on the depth of response that can be expected on initial treatment. Despite these advances, disease relapse remains inevitable in most patients and brings with it a different set of priorities for therapy. The most recent wave of novel agents may have a particular impact in the relapsed setting. In this review, we examine the evidence currently available from clinical trials for the use of novel agents, particularly in the formation of triplet therapy. We consider data supporting the addition of the proteasome inhibitors carfilzomib and ixazomib, or the monoclonal antibodies elotuzumab or daratumumab, to a treatment backbone of lenalidomide and dexamethasone. The clinical data set is less well developed for the addition of a third agent to the combination of bortezomib and dexamethasone; nonetheless, data are presented supporting the addition of the histone deacetylase inhibitor panobinostat, or elotuzumab or daratumumab. While acknowledging the lack of head-to-head data on which to base comparisons between the numerous regimens, we collate the latest data in order to provide a basis on which to make clinical decisions in this rapidly advancing field. © 2017 John Wiley & Sons Ltd.

Auditory proactive interference in monkeys: The role of stimulus set size and intertrial interval

PubMed Central

Bigelow, James; Poremba, Amy

2013-01-01

We conducted two experiments to examine the influence of stimulus set size (the number of stimuli that are used throughout the session) and intertrial interval (ITI, the elapsed time between trials) in auditory short-term memory in monkeys. We used an auditory delayed matching-to-sample task wherein the animals had to indicate whether two sounds separated by a 5-s retention interval were the same (match trials) or different (non-match trials). In Experiment 1, we randomly assigned a stimulus set size of 2, 4, 8, 16, 32, 64, or 192 (trial unique) for each session of 128 trials. Consistent with previous visual studies, overall accuracy was consistently lower when smaller stimulus set sizes were used. Further analyses revealed that these effects were primarily caused by an increase in incorrect “same” responses on non-match trials. In Experiment 2, we held the stimulus set size constant at four for each session and alternately set the ITI at 5, 10, or 20 s. Overall accuracy improved by increasing the ITI from 5 to 10 s, but the 10 and 20 s conditions were the same. As in Experiment 1, the overall decrease in accuracy during the 5-s condition was caused by a greater number of false “match” responses on non-match trials. Taken together, Experiments 1 and 2 show that auditory short-term memory in monkeys is highly susceptible to PI caused by stimulus repetition. Additional analyses from Experiment 1 suggest that monkeys may make same/different judgments based on a familiarity criterion that is adjusted by error-related feedback. PMID:23526232

Drug-resistant tuberculosis clinical trials: proposed core research definitions in adults.

PubMed

Furin, J; Alirol, E; Allen, E; Fielding, K; Merle, C; Abubakar, I; Andersen, J; Davies, G; Dheda, K; Diacon, A; Dooley, K E; Dravnice, G; Eisenach, K; Everitt, D; Ferstenberg, D; Goolam-Mahomed, A; Grobusch, M P; Gupta, R; Harausz, E; Harrington, M; Horsburgh, C R; Lienhardt, C; McNeeley, D; Mitnick, C D; Nachman, S; Nahid, P; Nunn, A J; Phillips, P; Rodriguez, C; Shah, S; Wells, C; Thomas-Nyang'wa, B; du Cros, P

2016-03-01

Drug-resistant tuberculosis (DR-TB) is a growing public health problem, and for the first time in decades, new drugs for the treatment of this disease have been developed. These new drugs have prompted strengthened efforts in DR-TB clinical trials research, and there are now multiple ongoing and planned DR-TB clinical trials. To facilitate comparability and maximise policy impact, a common set of core research definitions is needed, and this paper presents a core set of efficacy and safety definitions as well as other important considerations in DR-TB clinical trials work. To elaborate these definitions, a search of clinical trials registries, published manuscripts and conference proceedings was undertaken to identify groups conducting trials of new regimens for the treatment of DR-TB. Individuals from these groups developed the core set of definitions presented here. Further work is needed to validate and assess the utility of these definitions but they represent an important first step to ensure there is comparability in clinical trials on multidrug-resistant TB.

Perturbation corrections to Koopmans' theorem. V - A study with large basis sets

NASA Technical Reports Server (NTRS)

Chong, D. P.; Langhoff, S. R.

1982-01-01

The vertical ionization potentials of N2, F2 and H2O were calculated by perturbation corrections to Koopmans' theorem using six different basis sets. The largest set used includes several sets of polarization functions. Comparison is made with measured values and with results of computations using Green's functions.

A new basis set for molecular bending degrees of freedom.

PubMed

Jutier, Laurent

2010-07-21

We present a new basis set as an alternative to Legendre polynomials for the variational treatment of bending vibrational degrees of freedom in order to highly reduce the number of basis functions. This basis set is inspired from the harmonic oscillator eigenfunctions but is defined for a bending angle in the range theta in [0:pi]. The aim is to bring the basis functions closer to the final (ro)vibronic wave functions nature. Our methodology is extended to complicated potential energy surfaces, such as quasilinearity or multiequilibrium geometries, by using several free parameters in the basis functions. These parameters allow several density maxima, linear or not, around which the basis functions will be mainly located. Divergences at linearity in integral computations are resolved as generalized Legendre polynomials. All integral computations required for the evaluation of molecular Hamiltonian matrix elements are given for both discrete variable representation and finite basis representation. Convergence tests for the low energy vibronic states of HCCH(++), HCCH(+), and HCCS are presented.

Setting up a clinical trial for a novel disease: a case study of the Doxycycline for the Treatment of Nodding Syndrome Trial – challenges, enablers and lessons learned

PubMed Central

Anguzu, Ronald; Akun, Pamela R; Ogwang, Rodney; Shour, Abdul Rahman; Sekibira, Rogers; Ningwa, Albert; Nakamya, Phellister; Abbo, Catherine; Mwaka, Amos D; Opar, Bernard; Idro, Richard

2018-01-01

ABSTRACT A large amount of preparation goes into setting up trials. Different challenges and lessons are experienced. Our trial, testing a treatment for nodding syndrome, an acquired neurological disorder of unknown cause affecting thousands of children in Eastern Africa, provides a unique case study. As part of a study to determine the aetiology, understand pathogenesis and develop specific treatment, we set up a clinical trial in a remote district hospital in Uganda. This paper describes our experiences and documents supportive structures (enablers), challenges faced and lessons learned during set-up of the trial. Protocol development started in September 2015 with phased recruitment of a critical study team. The team spent 12 months preparing trial documents, procurement and training on procedures. Potential recruitment sites were pre-visited, and district and local leaders met as key stakeholders. Key enablers were supportive local leadership and investment by the district and Ministry of Health. The main challenges were community fears about nodding syndrome, adverse experiences of the community during previous research and political involvement. Other challenges included the number and delays in protocol approvals and lengthy procurement processes. This hard-to-reach area has frequent power and Internet fluctuations, which may affect cold chains for study samples, communication and data management. These concerns decreased with a pilot community engagement programme. Experiences and lessons learnt can reduce the duration of processes involved in trial-site set-up. A programme of community engagement and local leader involvement may be key to the success of a trial and in reducing community opposition towards participation in research. PMID:29382251

Setting up a clinical trial for a novel disease: a case study of the Doxycycline for the Treatment of Nodding Syndrome Trial - challenges, enablers and lessons learned.

PubMed

Anguzu, Ronald; Akun, Pamela R; Ogwang, Rodney; Shour, Abdul Rahman; Sekibira, Rogers; Ningwa, Albert; Nakamya, Phellister; Abbo, Catherine; Mwaka, Amos D; Opar, Bernard; Idro, Richard

2018-01-01

A large amount of preparation goes into setting up trials. Different challenges and lessons are experienced. Our trial, testing a treatment for nodding syndrome, an acquired neurological disorder of unknown cause affecting thousands of children in Eastern Africa, provides a unique case study. As part of a study to determine the aetiology, understand pathogenesis and develop specific treatment, we set up a clinical trial in a remote district hospital in Uganda. This paper describes our experiences and documents supportive structures (enablers), challenges faced and lessons learned during set-up of the trial. Protocol development started in September 2015 with phased recruitment of a critical study team. The team spent 12 months preparing trial documents, procurement and training on procedures. Potential recruitment sites were pre-visited, and district and local leaders met as key stakeholders. Key enablers were supportive local leadership and investment by the district and Ministry of Health. The main challenges were community fears about nodding syndrome, adverse experiences of the community during previous research and political involvement. Other challenges included the number and delays in protocol approvals and lengthy procurement processes. This hard-to-reach area has frequent power and Internet fluctuations, which may affect cold chains for study samples, communication and data management. These concerns decreased with a pilot community engagement programme. Experiences and lessons learnt can reduce the duration of processes involved in trial-site set-up. A programme of community engagement and local leader involvement may be key to the success of a trial and in reducing community opposition towards participation in research.

Challenges and impact of conducting vaccine trials in Asia and Africa

PubMed Central

Kochhar, Sonali

2013-01-01

Immunization is one of the most beneficial and cost-effective disease prevention measures. There are global efforts to develop new vaccines for disease control. The vaccine clinical trials must be conducted in the countries where they will be used. This has led to vaccine trials being conducted across Asia and Africa where there is a high burden of infectious diseases. The setup and successful conduct of International standard GCP vaccine trials across trial centers located in resource constrained settings are challenging. The challenges, ethical considerations and impact of the implementation of clinical trials in low-resource settings are highlighted here to help vaccine development programs successfully conduct such trials. PMID:23321645

Conflict Adaptation Depends on Task Structure

ERIC Educational Resources Information Center

Akcay, Caglar; Hazeltine, Eliot

2008-01-01

The dependence of the Simon effect on the correspondence of the previous trial can be explained by the conflict-monitoring theory, which holds that a control system adjusts automatic activation from irrelevant stimulus information (conflict adaptation) on the basis of the congruency of the previous trial. The authors report on 4 experiments…

Biological Basis for Chemoprevention of Ovarian Cancer

DTIC Science & Technology

2000-10-01

potent apoptotic effect on ovarian epithelial cells, the use of levonorgestrel in chemoprevention of ovarian cancer is being explored in chickens and women...A chemoprevention trial is ongoing in chickens and we will begin a trial to determine whether levonorgestrel induces apoptosis in the ovarian epithelium of women undergoing oophorectomy.

Progress on core outcome sets for critical care research.

PubMed

Blackwood, Bronagh; Marshall, John; Rose, Louise

2015-10-01

Appropriate selection and definition of outcome measures are essential for clinical trials to be maximally informative. Core outcome sets (an agreed, standardized collection of outcomes measured and reported in all trials for a specific clinical area) were developed due to established inconsistencies in trial outcome selection. This review discusses the rationale for, and methods of, core outcome set development, as well as current initiatives in critical care. Recent systematic reviews of reported outcomes and measurement instruments relevant to the critically ill highlight inconsistencies in outcome selection, definition, and measurement, thus establishing the need for core outcome sets. Current critical care initiatives include development of core outcome sets for trials aimed at reducing mechanical ventilation duration; rehabilitation following critical illness; long-term outcomes in acute respiratory failure; and epidemic and pandemic studies of severe acute respiratory infection. Development and utilization of core outcome sets for studies relevant to the critically ill is in its infancy compared to other specialties. Notwithstanding, core outcome set development frameworks and guidelines are available, several sets are in various stages of development, and there is strong support from international investigator-led collaborations including the International Forum for Acute Care Trialists.

Feasibility study of a single-blind randomised controlled trial of an occupational therapy intervention.

PubMed

Gantschnig, Brigitte E; Nilsson, Ingeborg; Fisher, Anne G; Künzle, Christoph; Page, Julie

2016-07-01

Several factors facilitate or hinder efficacy research in occupational therapy. Strategies are needed, therefore, to support the successful implementation of trials. To assess the feasibility of conducting a randomised controlled trial (RCT). The main feasibility objectives of this study were to assess the process, resources, management, and scientific basis of a trial RCT. A total of 10 occupational therapists, between the ages of 30 and 55 (M 43.4; SD 8.3) with seven to 26 years' (M 14.3; SD 6.1) experience, participated in this study. Qualitative data collected included minutes of meetings, reports, and field notes. The data were analysed based on the principles of content analysis, using feasibility objectives as the main categories. Data analysis revealed strengths in relation to retention and inclusion criteria of participants, the study protocol, study organisation, and the competence of researchers. Weaknesses were found related to recruitment, randomisation, data collection, time for training and communication, commitment, and design. The findings indicated that there are several factors which had a considerable impact on the implementation of an RCT in practice. However, it was useful to assess methods and procedures of the trial RCT as a basis to refine research plans.

The CONSENSUS study: protocol for a mixed methods study to establish which outcomes should be included in a core outcome set for oropharyngeal cancer.

PubMed

Waters, Aoife Mi; Tudur Smith, Catrin; Young, Bridget; Jones, Terry M

2014-05-13

The incidence of oropharyngeal cancer is increasing in the developed world. This has led to a large rise in research activity and clinical trials in this area, yet there is no consensus on which outcomes should be measured. As a result, the outcomes measured often differ between trials of comparable interventions, making the combination or comparison of results between trials impossible. Outcomes may also be 'cherry-picked', such that favourable results are reported, and less favourable results withheld. The development of a minimum outcome reporting standard, known as a core outcome set, goes some way to addressing these problems. Core outcome sets are ideally developed using a patient-centred approach so that the outcomes measured are relevant to patients and clinical practice. Core outcome sets drive up the quality and relevance of research by ensuring that the right outcomes are consistently measured and reported in trials in specific areas of health or healthcare. This is a mixed methods study involving three phases to develop a core outcome set for oropharyngeal cancer clinical trials. Firstly, a systematic review will establish which outcomes are measured in published oropharyngeal cancer randomised controlled trials (RCTs). Secondly, qualitative interviews with patients and carers in the UK and the USA will aim to establish which outcomes are important to these stakeholders. Data from these first two stages will be used to develop a comprehensive list of outcomes to be considered for inclusion in the core outcome set. In the third stage, patients and clinicians will participate in an iterative consensus exercise known as a Delphi study to refine the contents of the core outcome set. This protocol lays out the methodology to be implemented in the CONSENSUS study. A core outcome set defines a minimum outcome reporting standard for clinical trials in a particular area of health or healthcare. Its consistent implementation in oropharyngeal cancer clinical trials will improve the quality and relevance of research. This study is registered at the National Institute for Health Research (NIHR) Clinical Research Network (CRN) portfolio, ID 13823 (17 January 2013).

Extrapolating MP2 and CCSD explicitly correlated correlation energies to the complete basis set limit with first and second row correlation consistent basis sets

NASA Astrophysics Data System (ADS)

Hill, J. Grant; Peterson, Kirk A.; Knizia, Gerald; Werner, Hans-Joachim

2009-11-01

Accurate extrapolation to the complete basis set (CBS) limit of valence correlation energies calculated with explicitly correlated MP2-F12 and CCSD(T)-F12b methods have been investigated using a Schwenke-style approach for molecules containing both first and second row atoms. Extrapolation coefficients that are optimal for molecular systems containing first row elements differ from those optimized for second row analogs, hence values optimized for a combined set of first and second row systems are also presented. The new coefficients are shown to produce excellent results in both Schwenke-style and equivalent power-law-based two-point CBS extrapolations, with the MP2-F12/cc-pV(D,T)Z-F12 extrapolations producing an average error of just 0.17 mEh with a maximum error of 0.49 for a collection of 23 small molecules. The use of larger basis sets, i.e., cc-pV(T,Q)Z-F12 and aug-cc-pV(Q,5)Z, in extrapolations of the MP2-F12 correlation energy leads to average errors that are smaller than the degree of confidence in the reference data (˜0.1 mEh). The latter were obtained through use of very large basis sets in MP2-F12 calculations on small molecules containing both first and second row elements. CBS limits obtained from optimized coefficients for conventional MP2 are only comparable to the accuracy of the MP2-F12/cc-pV(D,T)Z-F12 extrapolation when the aug-cc-pV(5+d)Z and aug-cc-pV(6+d)Z basis sets are used. The CCSD(T)-F12b correlation energy is extrapolated as two distinct parts: CCSD-F12b and (T). While the CCSD-F12b extrapolations with smaller basis sets are statistically less accurate than those of the MP2-F12 correlation energies, this is presumably due to the slower basis set convergence of the CCSD-F12b method compared to MP2-F12. The use of larger basis sets in the CCSD-F12b extrapolations produces correlation energies with accuracies exceeding the confidence in the reference data (also obtained in large basis set F12 calculations). It is demonstrated that the use of the 3C(D) Ansatz is preferred for MP2-F12 CBS extrapolations. Optimal values of the geminal Slater exponent are presented for the diagonal, fixed amplitude Ansatz in MP2-F12 calculations, and these are also recommended for CCSD-F12b calculations.

Randomization Methods in Emergency Setting Trials: A Descriptive Review

ERIC Educational Resources Information Center

Corbett, Mark Stephen; Moe-Byrne, Thirimon; Oddie, Sam; McGuire, William

2016-01-01

Background: Quasi-randomization might expedite recruitment into trials in emergency care settings but may also introduce selection bias. Methods: We searched the Cochrane Library and other databases for systematic reviews of interventions in emergency medicine or urgent care settings. We assessed selection bias (baseline imbalances) in prognostic…

37 CFR 41.204 - Notice of basis for relief.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 false Notice of basis for relief. 41.204 Section 41.204 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE PRACTICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Patent Interferences § 41.204 Notice...

37 CFR 41.204 - Notice of basis for relief.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Notice of basis for relief. 41.204 Section 41.204 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE PRACTICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Patent Interferences § 41.204 Notice...

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. |

Predicting individual action switching in covert and continuous interactive tasks using the fluid events model

DOE PAGES

Radvansky, Gabriel A.; D’Mello, Sidney K.; Abbott, Robert G.; ...

2016-01-27

The Fluid Events Model is aimed at predicting changes in the actions people take on a moment-by-moment basis. In contrast with other research on action selection, this work does not investigate why some course of action was selected, but rather the likelihood of discontinuing the current course of action and selecting another in the near future. This is done using both task-based and experience-based factors. Prior work evaluated this model in the context of trial-by-trial, independent, interactive events, such as choosing how to copy a figure of a line drawing. In this paper, we extend this model to more covertmore » event experiences, such as reading narratives, as well as to continuous interactive events, such as playing a video game. To this end, the model was applied to existing data sets of reading time and event segmentation for written and picture stories. It was also applied to existing data sets of performance in a strategy board game, an aerial combat game, and a first person shooter game in which a participant’s current state was dependent on prior events. The results revealed that the model predicted behavior changes well, taking into account both the theoretically defined structure of the described events, as well as a person’s prior experience. Hence, theories of event cognition can benefit from efforts that take into account not only how events in the world are structured, but also how people experience those events.« less

Predicting Individual Action Switching in Covert and Continuous Interactive Tasks Using the Fluid Events Model

PubMed Central

Radvansky, Gabriel A.; D’Mello, Sidney K.; Abbott, Robert G.; Bixler, Robert E.

2016-01-01

The Fluid Events Model is aimed at predicting changes in the actions people take on a moment-by-moment basis. In contrast with other research on action selection, this work does not investigate why some course of action was selected, but rather the likelihood of discontinuing the current course of action and selecting another in the near future. This is done using both task-based and experience-based factors. Prior work evaluated this model in the context of trial-by-trial, independent, interactive events, such as choosing how to copy a figure of a line drawing. In this paper, we extend this model to more covert event experiences, such as reading narratives, as well as to continuous interactive events, such as playing a video game. To this end, the model was applied to existing data sets of reading time and event segmentation for written and picture stories. It was also applied to existing data sets of performance in a strategy board game, an aerial combat game, and a first person shooter game in which a participant’s current state was dependent on prior events. The results revealed that the model predicted behavior changes well, taking into account both the theoretically defined structure of the described events, as well as a person’s prior experience. Thus, theories of event cognition can benefit from efforts that take into account not only how events in the world are structured, but also how people experience those events. PMID:26858673

Predicting Individual Action Switching in Covert and Continuous Interactive Tasks Using the Fluid Events Model.

PubMed

Radvansky, Gabriel A; D'Mello, Sidney K; Abbott, Robert G; Bixler, Robert E

2016-01-01

The Fluid Events Model is aimed at predicting changes in the actions people take on a moment-by-moment basis. In contrast with other research on action selection, this work does not investigate why some course of action was selected, but rather the likelihood of discontinuing the current course of action and selecting another in the near future. This is done using both task-based and experience-based factors. Prior work evaluated this model in the context of trial-by-trial, independent, interactive events, such as choosing how to copy a figure of a line drawing. In this paper, we extend this model to more covert event experiences, such as reading narratives, as well as to continuous interactive events, such as playing a video game. To this end, the model was applied to existing data sets of reading time and event segmentation for written and picture stories. It was also applied to existing data sets of performance in a strategy board game, an aerial combat game, and a first person shooter game in which a participant's current state was dependent on prior events. The results revealed that the model predicted behavior changes well, taking into account both the theoretically defined structure of the described events, as well as a person's prior experience. Thus, theories of event cognition can benefit from efforts that take into account not only how events in the world are structured, but also how people experience those events.

Predicting individual action switching in covert and continuous interactive tasks using the fluid events model

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

Radvansky, Gabriel A.; D’Mello, Sidney K.; Abbott, Robert G.

The Fluid Events Model is aimed at predicting changes in the actions people take on a moment-by-moment basis. In contrast with other research on action selection, this work does not investigate why some course of action was selected, but rather the likelihood of discontinuing the current course of action and selecting another in the near future. This is done using both task-based and experience-based factors. Prior work evaluated this model in the context of trial-by-trial, independent, interactive events, such as choosing how to copy a figure of a line drawing. In this paper, we extend this model to more covertmore » event experiences, such as reading narratives, as well as to continuous interactive events, such as playing a video game. To this end, the model was applied to existing data sets of reading time and event segmentation for written and picture stories. It was also applied to existing data sets of performance in a strategy board game, an aerial combat game, and a first person shooter game in which a participant’s current state was dependent on prior events. The results revealed that the model predicted behavior changes well, taking into account both the theoretically defined structure of the described events, as well as a person’s prior experience. Hence, theories of event cognition can benefit from efforts that take into account not only how events in the world are structured, but also how people experience those events.« less

An Alternate Set of Basis Functions for the Electromagnetic Solution of Arbitrarily-Shaped, Three-Dimensional, Closed, Conducting Bodies Using Method of Moments

NASA Technical Reports Server (NTRS)

Mackenzie, Anne I.; Baginski, Michael E.; Rao, Sadasiva M.

2008-01-01

In this work, we present an alternate set of basis functions, each defined over a pair of planar triangular patches, for the method of moments solution of electromagnetic scattering and radiation problems associated with arbitrarily-shaped, closed, conducting surfaces. The present basis functions are point-wise orthogonal to the pulse basis functions previously defined. The prime motivation to develop the present set of basis functions is to utilize them for the electromagnetic solution of dielectric bodies using a surface integral equation formulation which involves both electric and magnetic cur- rents. However, in the present work, only the conducting body solution is presented and compared with other data.

Genetic and Environmental Pathways in Type 1 Diabetes Complications

DTIC Science & Technology

2010-09-26

setting? In the event that the project identifies a set of strongly predictive biomarkers an appropriate next step would be to approach TrialNet (see...http://www.diabetestrialnet.org). The TrialNet organization is a multi center study with the goal of identifying subjects for T1D prevention and...intervention trials. Children’s Hospital of Pittsburgh (CHP) is already acting as a clinical center for the TrialNet natural history study (Mahon et al

Interventions for promoting habitual exercise in people living with and beyond cancer.

PubMed

Bourke, Liam; Homer, Kate E; Thaha, Mohamed A; Steed, Liz; Rosario, Derek J; Robb, Karen A; Saxton, John M; Taylor, Stephanie J C

2013-09-24

The beneficial effects of regular exercise for people living with or beyond cancer are becoming apparent. However, how to promote exercise behaviour in sedentary cancer cohorts is not as well understood. A large majority of people living with or recovering from cancer do not meet exercise recommendations. Hence, reviewing the evidence on how to promote and sustain exercise behaviour is important. To assess the effects of interventions to promote exercise behaviour in sedentary people living with and beyond cancer and to address the following questions: Which interventions are most effective in improving aerobic fitness and skeletal muscle strength and endurance? What adverse effects are attributed to different exercise interventions? Which interventions are most effective in improving exercise behaviour amongst patients with different cancers? Which interventions are most likely to promote long-term (12 months or longer) exercise behaviour? What frequency of contact with exercise professionals is associated with increased exercise behaviour? What theoretical basis is most often associated with increased exercise behaviour? What behaviour change techniques are most often associated with increased exercise behaviour? We searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 8, 2012), MEDLINE, EMBASE, AMED, CINAHL, PsycLIT/PsycINFO, SportDiscus and PEDro from inception to August 2012. We also searched the grey literature, wrote to leading experts in the field, wrote to charities and searched reference lists of other recent systematic reviews. We included only randomised controlled trials (RCTs) that compared an exercise intervention with a usual care approach in sedentary people over the age of 18 with a homogenous primary cancer diagnosis. Two review authors working independently (LB and KH) screened all titles and abstracts to identify studies that might meet the inclusion criteria, or that cannot be safely excluded without assessment of the full text (e.g. when no abstract is available). All eligible papers were formally abstracted by at least two members of the review author team working independently (LB and KH) and using the data collection form. When possible, and if appropriate, we performed a fixed-effect meta-analysis of study outcomes. For continuous outcomes (e.g. cardiorespiratory fitness), we extracted the final value, the standard deviation of the outcome of interest and the number of participants assessed at follow-up in each treatment arm, to estimate standardised mean difference (SMD) between treatment arms. SMD was used, as investigators used heterogeneous methods to assess individual outcomes. If a meta-analysis was not possible or was not appropriate, we synthesised studies as a narrative. Fourteen trials were included in this review, involving a total of 648 participants. Only studies involving breast, prostate or colorectal cancer were identified as eligible. Just six trials incorporated a target level of exercise that could meet current recommendations. Only three trials were identified that attempted to objectively validate independent exercise behaviour with accelerometers or heart rate monitoring. Adherence to exercise interventions, which is crucial for understanding treatment dose, is often poorly reported. It is important to note that the fundamental metrics of exercise behaviour (i.e. frequency, intensity and duration, repetitions, sets and intensity of resistance training), although easy to devise and report, are seldom included in published clinical trials.None of the included trials reported that 75% or greater adherence (the stated primary outcome for this review) of the intervention group met current aerobic exercise recommendations at any given follow-up. Just two trials reported six weeks of resistance exercise behaviour that would meet the guideline recommendations. However, three trials reported adherence of 75% or greater to an aerobic exercise goal that was less than the current guideline recommendation of 150 minutes per week. All three incorporated both supervised and independent exercise components as part of the intervention, and none placed restrictions on the control group in terms of exercise behaviour. These three trials shared programme set goals and the following behaviour change techniques: generalisation of a target behaviour; prompting of self-monitoring of behaviour; and prompting of practise. Despite the uncertainty surrounding adherence in many of the included trials, interventions caused improvements in aerobic exercise tolerance at 8 to 12 weeks (from 7 studies, SMD 0.73, 95% confidence interval (CI) 0.51 to 0.95) in intervention participants compared with controls. At six months, aerobic exercise tolerance was also improved (from 5 studies, SMD 0.70, 95% CI 0.45 to 0.94), but it should be noted that four of the five trials used in this analysis had a high risk of bias, hence caution is warranted in interpretation of results. Attrition over the course of these interventions is typically low (median 6%). Interventions to promote exercise in cancer survivors who report better levels of adherence share some common behaviour change techniques. These involve setting programme goals, prompting practise and self-monitoring and encouraging participants to attempt to generalise behaviours learned in supervised exercise environments to other, non-supervised contexts. However, expecting most sedentary survivors to achieve current guideline recommendations of at least 150 minutes per week of aerobic exercise is likely to be unrealistic. As with all well-designed exercise programmes in any context, prescriptions should be designed around individual capabilities, and frequency, duration and intensity or sets, repetitions, intensity or resistance training should be generated on this basis.

Correction of energy-dependent systematic errors in dual-energy X-ray CT using a basis material coefficients transformation method

NASA Astrophysics Data System (ADS)

Goh, K. L.; Liew, S. C.; Hasegawa, B. H.

1997-12-01

Computer simulation results from our previous studies showed that energy dependent systematic errors exist in the values of attenuation coefficient synthesized using the basis material decomposition technique with acrylic and aluminum as the basis materials, especially when a high atomic number element (e.g., iodine from radiographic contrast media) was present in the body. The errors were reduced when a basis set was chosen from materials mimicking those found in the phantom. In the present study, we employed a basis material coefficients transformation method to correct for the energy-dependent systematic errors. In this method, the basis material coefficients were first reconstructed using the conventional basis materials (acrylic and aluminum) as the calibration basis set. The coefficients were then numerically transformed to those for a more desirable set materials. The transformation was done at the energies of the low and high energy windows of the X-ray spectrum. With this correction method using acrylic and an iodine-water mixture as our desired basis set, computer simulation results showed that accuracy of better than 2% could be achieved even when iodine was present in the body at a concentration as high as 10% by mass. Simulation work had also been carried out on a more inhomogeneous 2D thorax phantom of the 3D MCAT phantom. The results of the accuracy of quantitation were presented here.

Dispersion corrected hartree-fock and density functional theory for organic crystal structure prediction.

PubMed

Brandenburg, Jan Gerit; Grimme, Stefan

2014-01-01

We present and evaluate dispersion corrected Hartree-Fock (HF) and Density Functional Theory (DFT) based quantum chemical methods for organic crystal structure prediction. The necessity of correcting for missing long-range electron correlation, also known as van der Waals (vdW) interaction, is pointed out and some methodological issues such as inclusion of three-body dispersion terms are discussed. One of the most efficient and widely used methods is the semi-classical dispersion correction D3. Its applicability for the calculation of sublimation energies is investigated for the benchmark set X23 consisting of 23 small organic crystals. For PBE-D3 the mean absolute deviation (MAD) is below the estimated experimental uncertainty of 1.3 kcal/mol. For two larger π-systems, the equilibrium crystal geometry is investigated and very good agreement with experimental data is found. Since these calculations are carried out with huge plane-wave basis sets they are rather time consuming and routinely applicable only to systems with less than about 200 atoms in the unit cell. Aiming at crystal structure prediction, which involves screening of many structures, a pre-sorting with faster methods is mandatory. Small, atom-centered basis sets can speed up the computation significantly but they suffer greatly from basis set errors. We present the recently developed geometrical counterpoise correction gCP. It is a fast semi-empirical method which corrects for most of the inter- and intramolecular basis set superposition error. For HF calculations with nearly minimal basis sets, we additionally correct for short-range basis incompleteness. We combine all three terms in the HF-3c denoted scheme which performs very well for the X23 sublimation energies with an MAD of only 1.5 kcal/mol, which is close to the huge basis set DFT-D3 result.

Comparison of fMRI analysis methods for heterogeneous BOLD responses in block design studies.

PubMed

Liu, Jia; Duffy, Ben A; Bernal-Casas, David; Fang, Zhongnan; Lee, Jin Hyung

2017-02-15

A large number of fMRI studies have shown that the temporal dynamics of evoked BOLD responses can be highly heterogeneous. Failing to model heterogeneous responses in statistical analysis can lead to significant errors in signal detection and characterization and alter the neurobiological interpretation. However, to date it is not clear that, out of a large number of options, which methods are robust against variability in the temporal dynamics of BOLD responses in block-design studies. Here, we used rodent optogenetic fMRI data with heterogeneous BOLD responses and simulations guided by experimental data as a means to investigate different analysis methods' performance against heterogeneous BOLD responses. Evaluations are carried out within the general linear model (GLM) framework and consist of standard basis sets as well as independent component analysis (ICA). Analyses show that, in the presence of heterogeneous BOLD responses, conventionally used GLM with a canonical basis set leads to considerable errors in the detection and characterization of BOLD responses. Our results suggest that the 3rd and 4th order gamma basis sets, the 7th to 9th order finite impulse response (FIR) basis sets, the 5th to 9th order B-spline basis sets, and the 2nd to 5th order Fourier basis sets are optimal for good balance between detection and characterization, while the 1st order Fourier basis set (coherence analysis) used in our earlier studies show good detection capability. ICA has mostly good detection and characterization capabilities, but detects a large volume of spurious activation with the control fMRI data. Copyright © 2016 Elsevier Inc. All rights reserved.

Point Set Denoising Using Bootstrap-Based Radial Basis Function.

PubMed

Liew, Khang Jie; Ramli, Ahmad; Abd Majid, Ahmad

2016-01-01

This paper examines the application of a bootstrap test error estimation of radial basis functions, specifically thin-plate spline fitting, in surface smoothing. The presence of noisy data is a common issue of the point set model that is generated from 3D scanning devices, and hence, point set denoising is one of the main concerns in point set modelling. Bootstrap test error estimation, which is applied when searching for the smoothing parameters of radial basis functions, is revisited. The main contribution of this paper is a smoothing algorithm that relies on a bootstrap-based radial basis function. The proposed method incorporates a k-nearest neighbour search and then projects the point set to the approximated thin-plate spline surface. Therefore, the denoising process is achieved, and the features are well preserved. A comparison of the proposed method with other smoothing methods is also carried out in this study.

Rank-order-selective neurons form a temporal basis set for the generation of motor sequences.

PubMed

Salinas, Emilio

2009-04-08

Many behaviors are composed of a series of elementary motor actions that must occur in a specific order, but the neuronal mechanisms by which such motor sequences are generated are poorly understood. In particular, if a sequence consists of a few motor actions, a primate can learn to replicate it from memory after practicing it for just a few trials. How do the motor and premotor areas of the brain assemble motor sequences so fast? The network model presented here reveals part of the solution to this problem. The model is based on experiments showing that, during the performance of motor sequences, some cortical neurons are always activated at specific times, regardless of which motor action is being executed. In the model, a population of such rank-order-selective (ROS) cells drives a layer of downstream motor neurons so that these generate specific movements at different times in different sequences. A key ingredient of the model is that the amplitude of the ROS responses must be modulated by sequence identity. Because of this modulation, which is consistent with experimental reports, the network is able not only to produce multiple sequences accurately but also to learn a new sequence with minimal changes in connectivity. The ROS neurons modulated by sequence identity thus serve as a basis set for constructing arbitrary sequences of motor responses downstream. The underlying mechanism is analogous to the mechanism described in parietal areas for generating coordinate transformations in the spatial domain.

RANK-ORDER-SELECTIVE NEURONS FORM A TEMPORAL BASIS SET FOR THE GENERATION OF MOTOR SEQUENCES

PubMed Central

Salinas, Emilio

2009-01-01

Many behaviors are composed of a series of elementary motor actions that must occur in a specific order, but the neuronal mechanisms by which such motor sequences are generated are poorly understood. In particular, if a sequence consists of a few motor actions, a primate can learn to replicate it from memory after practicing it for just a few trials. How do the motor and premotor areas of the brain assemble motor sequences so fast? The network model presented here reveals part of the solution to this problem. The model is based on experiments showing that, during the performance of motor sequences, some cortical neurons are always activated at specific times, regardless of which motor action is being executed. In the model, a population of such rank-order-selective (ROS) cells drives a layer of downstream motor neurons so that these generate specific movements at different times in different sequences. A key ingredient of the model is that the amplitude of the ROS responses must be modulated by sequence identity. Because of this modulation, which is consistent with experimental reports, the network is able not only to produce multiple sequences accurately but also to learn a new sequence with minimal changes in connectivity. The ROS neurons modulated by sequence identity thus serve as a basis set for constructing arbitrary sequences of motor responses downstream. The underlying mechanism is analogous to the mechanism described in parietal areas for generating coordinate transformations in the spatial domain. PMID:19357265

Systemic inflammatory responses to maximal versus submaximal lengthening contractions of the elbow flexors.

PubMed

Peake, Jonathan M; Nosaka, Kazunori; Muthalib, Makii; Suzuki, Katsuhiko

2006-01-01

We compared changes in markers of muscle damage and systemic inflammation after submaximal and maximal lengthening muscle contractions of the elbow flexors. Using a cross-over design, 10 healthy young men not involved in resistance training completed a submaximal trial (10 sets of 60 lengthening contractions at 10% maximum isometric strength, 1 min rest between sets), followed by a maximal trial (10 sets of three lengthening contractions at 100% maximum isometric strength, 3 min rest between sets). Lengthening contractions were performed on an isokinetic dynamometer. Opposite arms were used for the submaximal and maximal trials, and the trials were separated by a minimum of two weeks. Blood was sampled before, immediately after, 1 h, 3 h, and 1-4 d after each trial. Total leukocyte and neutrophil numbers, and the serum concentration of soluble tumor necrosis factor-alpha receptor 1 were elevated after both trials (P < 0.01), but there were no differences between the trials. Serum IL-6 concentration was elevated 3 h after the submaximal contractions (P < 0.01). The concentrations of serum tumor necrosis factor-alpha, IL-1 receptor antagonist, IL-10, granulocyte-colony stimulating factor and plasma C-reactive protein remained unchanged following both trials. Maximum isometric strength and range of motion decreased significantly (P < 0.001) after both trials, and were lower from 1-4 days after the maximal contractions compared to the submaximal contractions. Plasma myoglobin concentration and creatine kinase activity, muscle soreness and upper arm circumference all increased after both trials (P < 0.01), but were not significantly different between the trials. Therefore, there were no differences in markers of systemic inflammation, despite evidence of greater muscle damage following maximal versus submaximal lengthening contractions of the elbow flexors.

Algorithm for improving psychophysical threshold estimates by detecting sustained inattention in experiments using PEST.

PubMed

Rinderknecht, Mike D; Ranzani, Raffaele; Popp, Werner L; Lambercy, Olivier; Gassert, Roger

2018-05-10

Psychophysical procedures are applied in various fields to assess sensory thresholds. During experiments, sampled psychometric functions are usually assumed to be stationary. However, perception can be altered, for example by loss of attention to the presentation of stimuli, leading to biased data, which results in poor threshold estimates. The few existing approaches attempting to identify non-stationarities either detect only whether there was a change in perception, or are not suitable for experiments with a relatively small number of trials (e.g., [Formula: see text] 300). We present a method to detect inattention periods on a trial-by-trial basis with the aim of improving threshold estimates in psychophysical experiments using the adaptive sampling procedure Parameter Estimation by Sequential Testing (PEST). The performance of the algorithm was evaluated in computer simulations modeling inattention, and tested in a behavioral experiment on proprioceptive difference threshold assessment in 20 stroke patients, a population where attention deficits are likely to be present. Simulations showed that estimation errors could be reduced by up to 77% for inattentive subjects, even in sequences with less than 100 trials. In the behavioral data, inattention was detected in 14% of assessments, and applying the proposed algorithm resulted in reduced test-retest variability in 73% of these corrected assessments pairs. The novel algorithm complements existing approaches and, besides being applicable post hoc, could also be used online to prevent collection of biased data. This could have important implications in assessment practice by shortening experiments and improving estimates, especially for clinical settings.

Effectiveness of a structured motivational intervention including smoking cessation advice and spirometry information in the primary care setting: the ESPITAP study

PubMed Central

2011-01-01

Background There is current controversy about the efficacy of smoking cessation interventions that are based on information obtained by spirometry. The objective of this study is to evaluate the effectiveness in the primary care setting of structured motivational intervention to achieve smoking cessation, compared with usual clinical practice. Methods Design Multicentre randomized clinical trial with an intervention and a control group. Setting 12 primary care centres in the province of Tarragona (Spain). Subjects of study 600 current smokers aged between 35 and 70 years with a cumulative habit of more than 10 packs of cigarettes per year, attended in primary care for any reason and who did not meet any of the exclusion criteria for the study, randomly assigned to structured intervention or standard clinical attention. Intervention Usual advice to quit smoking by a general practitioner as well as a 20-minute personalized visit to provide detailed information about spirometry results, during which FEV1, FVC, FEF 25-75% and PEF measurements were discussed and interpreted in terms of theoretical values. Additional information included the lung age index (defined as the average age of a non-smoker with the same FEV1 as the study participant), comparing this with the chronological age to illustrate the pulmonary deterioration that results from smoking. Measurements Spirometry during the initial visit. Structured interview questionnaire administered at the primary care centre at the initial visit and at 12-month follow-up. Telephone follow-up interview at 6 months. At 12-month follow-up, expired CO was measured in patients who claimed to have quit smoking. Main variables Smoking cessation at 12 months. Analysis Data will be analyzed on the basis of "intention to treat" and the unit of analysis will be the individual smoker. Expected results Among active smokers treated in primary care we anticipate significantly higher smoking cessation in the intervention group than in the control group. Discussion Application of a motivational intervention based on structured information about spirometry results, improved abstinence rates among smokers seen in actual clinical practice conditions in primary care. Trial registration ClinicalTrial.gov, number NCT01194596. PMID:22078490

Activated protein C: biased for translation.

PubMed

Griffin, John H; Zlokovic, Berislav V; Mosnier, Laurent O

2015-05-07

The homeostatic blood protease, activated protein C (APC), can function as (1) an antithrombotic on the basis of inactivation of clotting factors Va and VIIIa; (2) a cytoprotective on the basis of endothelial barrier stabilization and anti-inflammatory and antiapoptotic actions; and (3) a regenerative on the basis of stimulation of neurogenesis, angiogenesis, and wound healing. Pharmacologic therapies using recombinant human and murine APCs indicate that APC provides effective acute or chronic therapies for a strikingly diverse range of preclinical injury models. APC reduces the damage caused by the following: ischemia/reperfusion in brain, heart, and kidney; pulmonary, kidney, and gastrointestinal inflammation; sepsis; Ebola virus; diabetes; and total lethal body radiation. For these beneficial effects, APC alters cell signaling networks and gene expression profiles by activating protease-activated receptors 1 and 3. APC's activation of these G protein-coupled receptors differs completely from thrombin's activation mechanism due to biased signaling via either G proteins or β-arrestin-2. To reduce APC-associated bleeding risk, APC variants were engineered to lack >90% anticoagulant activity but retain normal cell signaling. Such a neuroprotective variant, 3K3A-APC (Lys191-193Ala), has advanced to clinical trials for ischemic stroke. A rich data set of preclinical knowledge provides a solid foundation for potential translation of APC variants to future novel therapies. © 2015 by The American Society of Hematology.

Computational study of the electronic spectra of the rare gas fluorohydrides HRgF (Rg = Ar, Kr, Xe, Rn)

NASA Astrophysics Data System (ADS)

van Hoeve, Miriam D.; Klobukowski, Mariusz

2018-03-01

Simulation of the electronic spectra of HRgF (Rg = Ar, Kr, Xe, Rn) was carried out using the time-dependent density functional method, with the CAMB3LYP functional and several basis sets augmented with even-tempered diffuse functions. A full spectral assignment for the HRgF systems was done. The effect of the rare gas matrix on the HRgF (Rg = Ar and Kr) spectra was investigated and it was found that the matrix blue-shifted the spectra. Scalar relativistic effects on the spectra were also studied and it was found that while the excitation energies of HArF and HKrF were insignificantly affected by relativistic effects, most of the excitation energies of HXeF and HRnF were red-shifted. Spin-orbit coupling was found to significantly affect excitation energies in HRnF. Analysis of performance of the model core potential basis set relative to all-electron (AE) basis sets showed that the former basis set increased computational efficiency and gave results similar to those obtained with the AE basis set.

Midbond basis functions for weakly bound complexes

NASA Astrophysics Data System (ADS)

Shaw, Robert A.; Hill, J. Grant

2018-06-01

Weakly bound systems present a difficult problem for conventional atom-centred basis sets due to large separations, necessitating the use of large, computationally expensive bases. This can be remedied by placing a small number of functions in the region between molecules in the complex. We present compact sets of optimised midbond functions for a range of complexes involving noble gases, alkali metals and small molecules for use in high accuracy coupled -cluster calculations, along with a more robust procedure for their optimisation. It is shown that excellent results are possible with double-zeta quality orbital basis sets when a few midbond functions are added, improving both the interaction energy and the equilibrium bond lengths of a series of noble gas dimers by 47% and 8%, respectively. When used in conjunction with explicitly correlated methods, near complete basis set limit accuracy is readily achievable at a fraction of the cost that using a large basis would entail. General purpose auxiliary sets are developed to allow explicitly correlated midbond function studies to be carried out, making it feasible to perform very high accuracy calculations on weakly bound complexes.

Simple Test Functions in Meshless Local Petrov-Galerkin Methods

NASA Technical Reports Server (NTRS)

Raju, Ivatury S.

2016-01-01

Two meshless local Petrov-Galerkin (MLPG) methods based on two different trial functions but that use a simple linear test function were developed for beam and column problems. These methods used generalized moving least squares (GMLS) and radial basis (RB) interpolation functions as trial functions. These two methods were tested on various patch test problems. Both methods passed the patch tests successfully. Then the methods were applied to various beam vibration problems and problems involving Euler and Beck's columns. Both methods yielded accurate solutions for all problems studied. The simple linear test function offers considerable savings in computing efforts as the domain integrals involved in the weak form are avoided. The two methods based on this simple linear test function method produced accurate results for frequencies and buckling loads. Of the two methods studied, the method with radial basis trial functions is very attractive as the method is simple, accurate, and robust.

Hand-suture versus stapling for closure of loop ileostomy: HASTA-Trial: a study rationale and design for a randomized controlled trial

PubMed Central

2011-01-01

Background Colorectal cancer is the second most common tumor in developed countries, with a lifetime prevalence of 5%. About one third of these tumors are located in the rectum. Surgery in terms of low anterior resection with mesorectal excision is the central element in the treatment of rectal cancer being the only option for definite cure. Creating a protective diverting stoma prevents complications like anastomotic failure and meanwhile is the standard procedure. Bowel obstruction is one of the main and the clinically and economically most relevant complication following closure of loop ileostomy. The best surgical technique for closure of loop ileostomy has not been defined yet. Methods/Design A study protocol was developed on the basis of the only randomized controlled mono-center trial to solve clinical equipoise concerning the optimal surgical technique for closure of loop ileostomy after low anterior resection due to rectal cancer. The HASTA trial is a multi-center pragmatic randomized controlled surgical trial with two parallel groups to compare hand-suture versus stapling for closure of loop ileostomy. It will include 334 randomized patients undergoing closure of loop ileostomy after low anterior resection with protective ileostomy due to rectal cancer in approximately 20 centers consisting of German hospitals of all level of health care. The primary endpoint is the rate of bowel obstruction within 30 days after ileostomy closure. In addition, a set of surgical and general variables including quality of life will be analyzed with a follow-up of 12 months. An investigators meeting with a practical session will help to minimize performance bias and enforce protocol adherence. Centers are monitored centrally as well as on-site before and during recruitment phase to assure inclusion, treatment and follow up according to the protocol. Discussion Aim of the HASTA trial is to evaluate the efficacy of hand-suture versus stapling for closure of loop ileostomy in patients with rectal cancer. Trial registration German Clinical Trial Register Number: DRKS00000040 PMID:21303515

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.

Møller-Plesset perturbation energies and distances for HeC(20) extrapolated to the complete basis set limit.

PubMed

Varandas, A J C

2009-02-01

The potential energy surface for the C(20)-He interaction is extrapolated for three representative cuts to the complete basis set limit using second-order Møller-Plesset perturbation calculations with correlation consistent basis sets up to the doubly augmented variety. The results both with and without counterpoise correction show consistency with each other, supporting that extrapolation without such a correction provides a reliable scheme to elude the basis-set-superposition error. Converged attributes are obtained for the C(20)-He interaction, which are used to predict the fullerene dimer ones. Time requirements show that the method can be drastically more economical than the counterpoise procedure and even competitive with Kohn-Sham density functional theory for the title system.

Exact exchange-correlation potentials of singlet two-electron systems

NASA Astrophysics Data System (ADS)

Ryabinkin, Ilya G.; Ospadov, Egor; Staroverov, Viktor N.

2017-10-01

We suggest a non-iterative analytic method for constructing the exchange-correlation potential, v XC ( r ) , of any singlet ground-state two-electron system. The method is based on a convenient formula for v XC ( r ) in terms of quantities determined only by the system's electronic wave function, exact or approximate, and is essentially different from the Kohn-Sham inversion technique. When applied to Gaussian-basis-set wave functions, the method yields finite-basis-set approximations to the corresponding basis-set-limit v XC ( r ) , whereas the Kohn-Sham inversion produces physically inappropriate (oscillatory and divergent) potentials. The effectiveness of the procedure is demonstrated by computing accurate exchange-correlation potentials of several two-electron systems (helium isoelectronic series, H2, H3 + ) using common ab initio methods and Gaussian basis sets.

Effectiveness of Modular CBT for Child Anxiety in Elementary Schools

ERIC Educational Resources Information Center

Chiu, Angela W.; Langer, David A.; McLeod, Bryce D.; Har, Kim; Drahota, Amy; Galla, Brian M.; Jacobs, Jeffrey; Ifekwunigwe, Muriel; Wood, Jeffrey J.

2013-01-01

Most randomized controlled trials of cognitive-behavioral therapy (CBT) for children with anxiety disorders have evaluated treatment efficacy using recruited samples treated in research settings. Clinical trials in school settings are needed to determine if CBT can be effective when delivered in real world settings. This study evaluated a modular…

Correlation consistent basis sets for actinides. I. The Th and U atoms.

PubMed

Peterson, Kirk A

2015-02-21

New correlation consistent basis sets based on both pseudopotential (PP) and all-electron Douglas-Kroll-Hess (DKH) Hamiltonians have been developed from double- to quadruple-zeta quality for the actinide atoms thorium and uranium. Sets for valence electron correlation (5f6s6p6d), cc - pV nZ - PP and cc - pV nZ - DK3, as well as outer-core correlation (valence + 5s5p5d), cc - pwCV nZ - PP and cc - pwCV nZ - DK3, are reported (n = D, T, Q). The -PP sets are constructed in conjunction with small-core, 60-electron PPs, while the -DK3 sets utilized the 3rd-order Douglas-Kroll-Hess scalar relativistic Hamiltonian. Both series of basis sets show systematic convergence towards the complete basis set limit, both at the Hartree-Fock and correlated levels of theory, making them amenable to standard basis set extrapolation techniques. To assess the utility of the new basis sets, extensive coupled cluster composite thermochemistry calculations of ThFn (n = 2 - 4), ThO2, and UFn (n = 4 - 6) have been carried out. After accurately accounting for valence and outer-core correlation, spin-orbit coupling, and even Lamb shift effects, the final 298 K atomization enthalpies of ThF4, ThF3, ThF2, and ThO2 are all within their experimental uncertainties. Bond dissociation energies of ThF4 and ThF3, as well as UF6 and UF5, were similarly accurate. The derived enthalpies of formation for these species also showed a very satisfactory agreement with experiment, demonstrating that the new basis sets allow for the use of accurate composite schemes just as in molecular systems composed only of lighter atoms. The differences between the PP and DK3 approaches were found to increase with the change in formal oxidation state on the actinide atom, approaching 5-6 kcal/mol for the atomization enthalpies of ThF4 and ThO2. The DKH3 atomization energy of ThO2 was calculated to be smaller than the DKH2 value by ∼1 kcal/mol.

On the basis set convergence of electron–electron entanglement measures: helium-like systems

PubMed Central

Hofer, Thomas S.

2013-01-01

A systematic investigation of three different electron–electron entanglement measures, namely the von Neumann, the linear and the occupation number entropy at full configuration interaction level has been performed for the four helium-like systems hydride, helium, Li+ and Be2+ using a large number of different basis sets. The convergence behavior of the resulting energies and entropies revealed that the latter do in general not show the expected strictly monotonic increase upon increase of the one–electron basis. Overall, the three different entanglement measures show good agreement among each other, the largest deviations being observed for small basis sets. The data clearly demonstrates that it is important to consider the nature of the chemical system when investigating entanglement phenomena in the framework of Gaussian type basis sets: while in case of hydride the use of augmentation functions is crucial, the application of core functions greatly improves the accuracy in case of cationic systems such as Li+ and Be2+. In addition, numerical derivatives of the entanglement measures with respect to the nucleic charge have been determined, which proved to be a very sensitive probe of the convergence leading to qualitatively wrong results (i.e., the wrong sign) if too small basis sets are used. PMID:24790952

On the basis set convergence of electron-electron entanglement measures: helium-like systems.

PubMed

Hofer, Thomas S

2013-01-01

A systematic investigation of three different electron-electron entanglement measures, namely the von Neumann, the linear and the occupation number entropy at full configuration interaction level has been performed for the four helium-like systems hydride, helium, Li(+) and Be(2+) using a large number of different basis sets. The convergence behavior of the resulting energies and entropies revealed that the latter do in general not show the expected strictly monotonic increase upon increase of the one-electron basis. Overall, the three different entanglement measures show good agreement among each other, the largest deviations being observed for small basis sets. The data clearly demonstrates that it is important to consider the nature of the chemical system when investigating entanglement phenomena in the framework of Gaussian type basis sets: while in case of hydride the use of augmentation functions is crucial, the application of core functions greatly improves the accuracy in case of cationic systems such as Li(+) and Be(2+). In addition, numerical derivatives of the entanglement measures with respect to the nucleic charge have been determined, which proved to be a very sensitive probe of the convergence leading to qualitatively wrong results (i.e., the wrong sign) if too small basis sets are used.

78 FR 42529 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-16

... Stroke Special Emphasis Panel Stroke Trials Network NCCC SEP. Date: August 15, 2013. Time: 8:00 a.m. to...: National Institute of Neurological Disorders and Stroke Special Emphasis Panel Stroke Trial Network Sites... Related to Neurological Disorders; 93.854, Biological Basis Research in the Neurosciences, National...

Strategy Use and Strategy Choice in Fraction Magnitude Comparison

ERIC Educational Resources Information Center

Fazio, Lisa K.; DeWolf, Melissa; Siegler, Robert S.

2016-01-01

We examined, on a trial-by-trial basis, fraction magnitude comparison strategies of adults with more and less mathematical knowledge. College students with high mathematical proficiency used a large variety of strategies that were well tailored to the characteristics of the problems and that were guaranteed to yield correct performance if executed…

Orbital-Dependent Density Functionals for Chemical Catalysis

DTIC Science & Technology

2014-10-17

noncollinear density functional theory to show that the low-spin state of Mn3 in a model of the oxygen -evolving complex of photosystem II avoids...DK, which denotes the cc-pV5Z-DK basis set for 3d metals and hydrogen and the ma-cc- pV5Z-DK basis set for oxygen ) and to nonrelativistic all...cc-pV5Z basis set for oxygen ). As compared to NCBS-DK results, all ECP calculations perform worse than def2-TZVP all-electron relativistic

Electric dipole moment of diatomic molecules by configuration interaction. IV.

NASA Technical Reports Server (NTRS)

Green, S.

1972-01-01

The theory of basis set dependence in configuration interaction calculations is discussed, taking into account a perturbation model which is valid for small changes in the self-consistent field orbitals. It is found that basis set corrections are essentially additive through first order. It is shown that an error found in a previously published dipole moment calculation by Green (1972) for the metastable first excited state of CO was indeed due to an inadequate basis set as claimed.

The 'Outcome Reporting in Brief Intervention Trials: Alcohol' (ORBITAL) framework: protocol to determine a core outcome set for efficacy and effectiveness trials of alcohol screening and brief intervention.

PubMed

Shorter, G W; Heather, N; Bray, Jeremy W; Giles, E L; Holloway, A; Barbosa, C; Berman, A H; O'Donnell, A J; Clarke, M; Stockdale, K J; Newbury-Birch, D

2017-12-22

The evidence base to assess the efficacy and effectiveness of alcohol brief interventions (ABI) is weakened by variation in the outcomes measured and by inconsistent reporting. The 'Outcome Reporting in Brief Intervention Trials: Alcohol' (ORBITAL) project aims to develop a core outcome set (COS) and reporting guidance for its use in future trials of ABI in a range of settings. An international Special Interest Group was convened through INEBRIA (International Network on Brief Interventions for Alcohol and Other Drugs) to inform the development of a COS for trials of ABI. ORBITAL will incorporate a systematic review to map outcomes used in efficacy and effectiveness trials of ABI and their measurement properties, using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. This will support a multi-round Delphi study to prioritise outcomes. Delphi panellists will be drawn from a range of settings and stakeholder groups, and the Delphi study will also be used to determine if a single COS is relevant for all settings. A consensus meeting with key stakeholder representation will determine the final COS and associated guidance for its use in trials of ABI. ORBITAL will develop a COS for alcohol screening and brief intervention trials, with outcomes stratified into domains and guidance on outcome measurement instruments. The standardisation of ABI outcomes and their measurement will support the ongoing development of ABI studies and a systematic synthesis of emerging research findings. We will track the extent to which the COS delivers on this promise through an exploration of the use of the guidance in the decade following COS publication.

THE TESTOSTERONE TRIALS: THE DESIGN OF SEVEN COORDINATED TRIALS TO DETERMINE IF TESTOSTERONE TREATMENT BENEFITS ELDERLY MEN

PubMed Central

Snyder, Peter J; Ellenberg, Susan S; Cunningham, Glenn R; Matsumoto, Alvin M; Bhasin, Shalender; Barrett-Connor, Elizabeth; Gill, Thomas M; Farrar, John T; Cella, David; Rosen, Raymond C; Resnick, Susan M; Swerdloff, Ronald S; Cauley, Jane A; Cifelli, Denise; Fluharty, Laura; Pahor, Marco; Ensrud, Kristine E; Lewis, Cora E; Molitch, Mark E; Crandall, Jill P; Wang, Christina; Budoff, Matthew J; Wenger, Nanette K; Mohler, Emile R; Bild, Diane E; Cook, Nakela L; Keaveny, Tony M; Kopperdahl, David L; Lee, David; Schwartz, Ann V; Storer, Thomas W; Ershler, William B; Roy, Cindy N; Raffel, Leslie J; Romashkan, Sergei; Hadley, Evan

2014-01-01

Background The prevalence of low testosterone levels in men increases with age, as does the prevalence of decreased mobility, sexual function, self-perceived vitality, cognitive abilities, bone mineral density, and glucose tolerance, and of increased anemia and coronary artery disease. Similar changes occur in men who have low serum testosterone concentrations due to known pituitary or testicular disease, and testosterone treatment improves the abnormalities. Prior studies of the effect of testosterone treatment in elderly men, however, have produced equivocal results. Purpose To describe a coordinated set of clinical trials designed to avoid the pitfalls of prior studies and determine definitively if testosterone treatment of elderly men with low testosterone is efficacious in improving symptoms and objective measures of age-associated conditions. Methods We present the scientific and clinical rationale for the decisions made in the design of this trial. Results We designed The Testosterone Trials as a coordinated set of seven trials to determine if testosterone treatment of elderly men with low serum testosterone concentrations and also symptoms and objective evidence of impaired mobility and/or diminished libido and/or reduced vitality would be efficacious in improving mobility (Physical Function Trial), sexual function (Sexual Function Trial), fatigue (Vitality Trial), cognitive function (Cognitive Function Trial), hemoglobin (Anemia Trial), bone density (Bone Trial), and coronary artery plaque volume (Cardiovascular Trial). The scientific advantages of this coordination were common eligibility criteria, treatment and monitoring and the ability to pool safety data. The logistical advantages were a single steering committee, data coordinating center and data safety monitoring board (DSMB), the same clinical trial sites, and the possibility of men participating in multiple trials. The major consideration in subject selection was setting the eligibility criterion for serum testosterone low enough to ensure that the men were unequivocally testosterone deficient, but not so low as to preclude sufficient enrollment or eventual generalizability of the results. The major considerations in choosing primary end points for each trial were identifying those of the highest clinical importance and identifying the minimum clinically important differences between treatment arms for sample size estimation. Potential Limitations Setting the serum testosterone concentration sufficiently low to ensure that most men would be unequivocally testosterone deficient, as well as many other entry criteria, resulted in screening approximately 30 men in person to randomize one subject. Conclusions The Testosterone Trials were designed to determine definitively if testosterone treatment of elderly men with low testosterone would have any clinical benefit. Designing The Testosterone Trials as a coordinated set of seven trials afforded many important scientific and logistical advantages but required an intensive recruitment and screening effort. PMID:24686158

New Basis Functions for the Electromagnetic Solution of Arbitrarily-shaped, Three Dimensional Conducting Bodies Using Method of Moments

NASA Technical Reports Server (NTRS)

Mackenzie, Anne I.; Baginski, Michael E.; Rao, Sadasiva M.

2007-01-01

In this work, we present a new set of basis functions, de ned over a pair of planar triangular patches, for the solution of electromagnetic scattering and radiation problems associated with arbitrarily-shaped surfaces using the method of moments solution procedure. The basis functions are constant over the function subdomain and resemble pulse functions for one and two dimensional problems. Further, another set of basis functions, point-wise orthogonal to the first set, is also de ned over the same function space. The primary objective of developing these basis functions is to utilize them for the electromagnetic solution involving conducting, dielectric, and composite bodies. However, in the present work, only the conducting body solution is presented and compared with other data.

New Basis Functions for the Electromagnetic Solution of Arbitrarily-shaped, Three Dimensional Conducting Bodies using Method of Moments

NASA Technical Reports Server (NTRS)

Mackenzie, Anne I.; Baginski, Michael E.; Rao, Sadasiva M.

2008-01-01

In this work, we present a new set of basis functions, defined over a pair of planar triangular patches, for the solution of electromagnetic scattering and radiation problems associated with arbitrarily-shaped surfaces using the method of moments solution procedure. The basis functions are constant over the function subdomain and resemble pulse functions for one and two dimensional problems. Further, another set of basis functions, point-wise orthogonal to the first set, is also defined over the same function space. The primary objective of developing these basis functions is to utilize them for the electromagnetic solution involving conducting, dielectric, and composite bodies. However, in the present work, only the conducting body solution is presented and compared with other data.

Exposure Matching for Extrapolation of Efficacy in Pediatric Drug Development

PubMed Central

Mulugeta, Yeruk; Barrett, Jeffrey S.; Nelson, Robert; Eshete, Abel Tilahun; Mushtaq, Alvina; Yao, Lynne; Glasgow, Nicole; Mulberg, Andrew E.; Gonzalez, Daniel; Green, Dionna; Florian, Jeffry; Krudys, Kevin; Seo, Shirley; Kim, Insook; Chilukuri, Dakshina; Burckart, Gilbert J.

2017-01-01

During drug development, matching adult systemic exposures of drugs is a common approach for dose selection in pediatric patients when efficacy is partially or fully extrapolated. This is a systematic review of approaches used for matching adult systemic exposures as the basis for dose selection in pediatric trials submitted to the U.S. Food and Drug Administration (FDA) between 1998 and 2012. The trial design of pediatric pharmacokinetic (PK) studies and the pediatric and adult systemic exposure data were obtained from FDA publicly available databases containing reviews of pediatric trials. Exposure matching approaches that were used as the basis for pediatric dose selection were reviewed. The PK data from the adult and pediatric populations were used to quantify exposure agreement between the two patient populations. The main measures were the pediatric PK studies trial design elements and drug systemic exposures (adult and pediatric). There were 31 products (86 trials) with full or partial extrapolation of efficacy with an available PK assessment. Pediatric exposures had a range of mean Cmax and AUC ratios (pediatric/adult) of 0.63-4.19 and 0.36-3.60 respectively. Seven of the 86 trials (8.1%) had a pre-defined acceptance boundary used to match adult exposures. The key PK parameter was consistently predefined for antiviral and anti-infective products. Approaches to match exposure in children and adults varied across products. A consistent approach for systemic exposure matching and evaluating pediatric PK studies is needed to guide future pediatric trials. PMID:27040726

Necessary Contributions of Human Frontal Lobe Subregions to Reward Learning in a Dynamic, Multidimensional Environment.

PubMed

Vaidya, Avinash R; Fellows, Lesley K

2016-09-21

Real-world decisions are typically made between options that vary along multiple dimensions, requiring prioritization of the important dimensions to support optimal choice. Learning in this setting depends on attributing decision outcomes to the dimensions with predictive relevance rather than to dimensions that are irrelevant and nonpredictive. This attribution problem is computationally challenging, and likely requires an interplay between selective attention and reward learning. Both these processes have been separately linked to the prefrontal cortex, but little is known about how they combine to support learning the reward value of multidimensional stimuli. Here, we examined the necessary contributions of frontal lobe subregions in attributing feedback to relevant and irrelevant dimensions on a trial-by-trial basis in humans. Patients with focal frontal lobe damage completed a demanding reward learning task where options varied on three dimensions, only one of which predicted reward. Participants with left lateral frontal lobe damage attributed rewards to irrelevant dimensions, rather than the relevant dimension. Damage to the ventromedial frontal lobe also impaired learning about the relevant dimension, but did not increase reward attribution to irrelevant dimensions. The results argue for distinct roles for these two regions in learning the value of multidimensional decision options under dynamic conditions, with the lateral frontal lobe required for selecting the relevant dimension to associate with reward, and the ventromedial frontal lobe required to learn the reward association itself. The real world is complex and multidimensional; how do we attribute rewards to predictive features when surrounded by competing cues? Here, we tested the critical involvement of human frontal lobe subregions in a probabilistic, multidimensional learning environment, asking whether focal lesions affected trial-by-trial attribution of feedback to relevant and irrelevant dimensions. The left lateral frontal lobe was required for filtering option dimensions to allow appropriate feedback attribution, while the ventromedial frontal lobe was necessary for learning the value of features in the relevant dimension. These findings argue that selective attention and associative learning processes mediated by anatomically distinct frontal lobe subregions are both critical for adaptive choice in more complex, ecologically valid settings. Copyright © 2016 the authors 0270-6474/16/369843-16$15.00/0.

European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP): a randomized trial.

PubMed

Landolfi, R; Marchioli, R

1997-01-01

Thrombotic complications characterize the clinical course of polycythemia vera (PV) and represent the main cause of morbidity and mortality. However, uncertainty still exists as to the benefit/risk ratio of aspirin prophylaxis in this setting. In vivo platelet biosynthesis of thromboxane A2 is enhanced and can be suppressed by low-dose aspirin in PV, thus providing a rationale for assessing the efficacy and safety of a low-dose aspirin regimen in these patients. The Gruppo Italiano Studio Policitemia Vera has recently performed a pilot study on 112 patients randomized to receive aspirin, 40 mg daily, or placebo and followed for 16 +/- 6 months (mean +/- SD). This study showed that low-dose aspirin is well tolerated in PV patients, and that a large-scale efficacy trial is feasible in this setting. In this article we report the protocol of the European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) study, which is a randomized trial designed to assess the risk/benefit ratio of low-dose aspirin in PV. To estimate the size and the follow-up duration required for the ECLAP trial, a retrospective analysis of the clinical epidemiology of a large PV population has recently been completed by the Gruppo Italiano Studio Policitemia Vera. On this basis, approximately 3500 patients will be enrolled in the ECLAP study with a follow-up of 3 to 4 years. The uncertainty principle will be used as the main eligibility criterion: Polycythemic patients of any age, having no clear indication for or contraindication to aspirin treatment, will be randomized in a double-blind fashion to receive oral aspirin (100 mg daily) or placebo. According to current therapeutic recommendations, the basic treatment of randomized patients should be aimed at maintaining the hematocrit value < or = 45% in subjects aged < or = 50, and hematocrit < 45% as well as platelet count < 400 x 10(9)/L in patients aged > 50. Randomization will be stratified by participating center. The study is funded by the European Union BIOMED 2 program.

A core outcome set for clinical trials in acute diarrhoea.

PubMed

Karas, Jacek; Ashkenazi, Shai; Guarino, Alfredo; Lo Vecchio, Andrea; Shamir, Raanan; Vandenplas, Yvan; Szajewska, Hania

2015-04-01

Core outcome sets are the baseline for what should be measured in clinical research and, thus, should serve as a guide for what should be collected and reported. The Consensus Group on Outcome Measures Made in Pediatric Enteral Nutrition Clinical Trials, established in 2012, agreed that consensus on a core set of outcomes with agreed-upon definitions that should be measured and reported in clinical trials was needed. To achieve this goal, six working groups (WGs) were setup, including WG on acute diarrhoea, whose main goal was to develop a core outcome set for trials in acute diarrhoea. The first step identified how published outcomes related to acute diarrhoea were reported. The second focused on the methodology for determining which outcomes to measure in clinical trials. The third employed a two-phase questionnaire study using the Delphi technique to define clinically important outcomes to clinicians and parents. For therapeutic studies, the five most important outcome measures were diarrhoea duration, degree of dehydration, need for hospitalisation (or duration of hospitalisation for inpatients), the proportion of patients recovered by 48 h and adverse effects. The prophylactic core outcome set included prevention of diarrhoea, prevention of dehydration, prevention of hospitalisation and adverse effects. The outcome sets for therapy and prevention can be recommended for use in future trials of patients with gastroenteritis. Their envisioned goal is to decrease study heterogeneity and to ease the comparability of studies. WG's next step is to determine how to measure the outcomes included in the core set. 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.

Operational Space Weather Models: Trials, Tribulations and Rewards

NASA Astrophysics Data System (ADS)

Schunk, R. W.; Scherliess, L.; Sojka, J. J.; Thompson, D. C.; Zhu, L.

2009-12-01

There are many empirical, physics-based, and data assimilation models that can probably be used for space weather applications and the models cover the entire domain from the surface of the Sun to the Earth’s surface. At Utah State University we developed two physics-based data assimilation models of the terrestrial ionosphere as part of a program called Global Assimilation of Ionospheric Measurements (GAIM). One of the data assimilation models is now in operational use at the Air Force Weather Agency (AFWA) in Omaha, Nebraska. This model is a Gauss-Markov Kalman Filter (GAIM-GM) model, and it uses a physics-based model of the ionosphere and a Kalman filter as a basis for assimilating a diverse set of real-time (or near real-time) measurements. The physics-based model is the Ionosphere Forecast Model (IFM), which is global and covers the E-region, F-region, and topside ionosphere from 90 to 1400 km. It takes account of five ion species (NO+, O2+, N2+, O+, H+), but the main output of the model is a 3-dimensional electron density distribution at user specified times. The second data assimilation model uses a physics-based Ionosphere-Plasmasphere Model (IPM) and an ensemble Kalman filter technique as a basis for assimilating a diverse set of real-time (or near real-time) measurements. This Full Physics model (GAIM-FP) is global, covers the altitude range from 90 to 30,000 km, includes six ions (NO+, O2+, N2+, O+, H+, He+), and calculates the self-consistent ionospheric drivers (electric fields and neutral winds). The GAIM-FP model is scheduled for delivery in 2012. Both of these GAIM models assimilate bottom-side Ne profiles from a variable number of ionosondes, slant TEC from a variable number of ground GPS/TEC stations, in situ Ne from four DMSP satellites, line-of-sight UV emissions measured by satellites, and occultation data. Quality control algorithms for all of the data types are provided as an integral part of the GAIM models and these models take account of latent data (up to 3 hours). The trials, tribulations and rewards of constructing and maintaining operational data assimilation models will be discussed.

Atomic Cholesky decompositions: a route to unbiased auxiliary basis sets for density fitting approximation with tunable accuracy and efficiency.

PubMed

Aquilante, Francesco; Gagliardi, Laura; Pedersen, Thomas Bondo; Lindh, Roland

2009-04-21

Cholesky decomposition of the atomic two-electron integral matrix has recently been proposed as a procedure for automated generation of auxiliary basis sets for the density fitting approximation [F. Aquilante et al., J. Chem. Phys. 127, 114107 (2007)]. In order to increase computational performance while maintaining accuracy, we propose here to reduce the number of primitive Gaussian functions of the contracted auxiliary basis functions by means of a second Cholesky decomposition. Test calculations show that this procedure is most beneficial in conjunction with highly contracted atomic orbital basis sets such as atomic natural orbitals, and that the error resulting from the second decomposition is negligible. We also demonstrate theoretically as well as computationally that the locality of the fitting coefficients can be controlled by means of the decomposition threshold even with the long-ranged Coulomb metric. Cholesky decomposition-based auxiliary basis sets are thus ideally suited for local density fitting approximations.

Atomic Cholesky decompositions: A route to unbiased auxiliary basis sets for density fitting approximation with tunable accuracy and efficiency

NASA Astrophysics Data System (ADS)

Aquilante, Francesco; Gagliardi, Laura; Pedersen, Thomas Bondo; Lindh, Roland

2009-04-01

Cholesky decomposition of the atomic two-electron integral matrix has recently been proposed as a procedure for automated generation of auxiliary basis sets for the density fitting approximation [F. Aquilante et al., J. Chem. Phys. 127, 114107 (2007)]. In order to increase computational performance while maintaining accuracy, we propose here to reduce the number of primitive Gaussian functions of the contracted auxiliary basis functions by means of a second Cholesky decomposition. Test calculations show that this procedure is most beneficial in conjunction with highly contracted atomic orbital basis sets such as atomic natural orbitals, and that the error resulting from the second decomposition is negligible. We also demonstrate theoretically as well as computationally that the locality of the fitting coefficients can be controlled by means of the decomposition threshold even with the long-ranged Coulomb metric. Cholesky decomposition-based auxiliary basis sets are thus ideally suited for local density fitting approximations.

Standard requirements for GCP-compliant data management in multinational clinical trials

PubMed Central

2011-01-01

Background A recent survey has shown that data management in clinical trials performed by academic trial units still faces many difficulties (e.g. heterogeneity of software products, deficits in quality management, limited human and financial resources and the complexity of running a local computer centre). Unfortunately, no specific, practical and open standard for both GCP-compliant data management and the underlying IT-infrastructure is available to improve the situation. For that reason the "Working Group on Data Centres" of the European Clinical Research Infrastructures Network (ECRIN) has developed a standard specifying the requirements for high quality GCP-compliant data management in multinational clinical trials. Methods International, European and national regulations and guidelines relevant to GCP, data security and IT infrastructures, as well as ECRIN documents produced previously, were evaluated to provide a starting point for the development of standard requirements. The requirements were produced by expert consensus of the ECRIN Working group on Data Centres, using a structured and standardised process. The requirements were divided into two main parts: an IT part covering standards for the underlying IT infrastructure and computer systems in general, and a Data Management (DM) part covering requirements for data management applications in clinical trials. Results The standard developed includes 115 IT requirements, split into 15 separate sections, 107 DM requirements (in 12 sections) and 13 other requirements (2 sections). Sections IT01 to IT05 deal with the basic IT infrastructure while IT06 and IT07 cover validation and local software development. IT08 to IT015 concern the aspects of IT systems that directly support clinical trial management. Sections DM01 to DM03 cover the implementation of a specific clinical data management application, i.e. for a specific trial, whilst DM04 to DM12 address the data management of trials across the unit. Section IN01 is dedicated to international aspects and ST01 to the competence of a trials unit's staff. Conclusions The standard is intended to provide an open and widely used set of requirements for GCP-compliant data management, particularly in academic trial units. It is the intention that ECRIN will use these requirements as the basis for the certification of ECRIN data centres. PMID:21426576

Statement of Facts for 1982 City-Wide Mock Trial Competitions. Vincent Taylor, Plaintiff v. Lance Memorial Hospital for Women, Raymond Miller, M.D., and Dorothy Dillon, R.N., Defendants. No. MT-82.

ERIC Educational Resources Information Center

National Inst. for Citizen Education in the Law, Washington, DC.

Prepared by the District of Columbia Street Law Project for its 11th annual city-wide mock trial competition, this instructional handout provides material for a civil trial over a disputed discriminatory termination of employment. Vincent Taylor claims that the Lance Memorial Hospital for Women fired him on the basis of his sex. The hospital…

EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti‐neutrophil cytoplasm antibody‐associated vasculitis

PubMed Central

Hellmich, Bernhard; Flossmann, Oliver; Gross, Wolfgang L; Bacon, Paul; Cohen‐Tervaert, Jan Willem; Guillevin, Loic; Jayne, David; Mahr, Alfred; Merkel, Peter A; Raspe, Heiner; Scott, David G I; Witter, James; Yazici, Hasan; Luqmani, Raashid A

2007-01-01

Objectives To develop the European League Against Rheumatism (EULAR) recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis. Methods An expert consensus group was formed consisting of rheumatologists, nephrologists and specialists in internal medicine representing five European countries and the USA, a clinical epidemiologist and representatives from regulatory agencies. Using an evidence‐based and expert opinion‐based approach in accordance with the standardised EULAR operating procedures, the group identified nine topics for a systematic literature search through a modified Delphi technique. On the basis of research questions posed by the group, recommendations were derived for conducting clinical studies and/or clinical trials in systemic vasculitis. Results Based on the results of the literature research, the expert committee concluded that sufficient evidence to formulate guidelines on conducting clinical trials was available only for anti‐neutrophil cytoplasm antibody‐associated vasculitides (AAV). It was therefore decided to focus the recommendations on these diseases. Recommendations for conducting clinical trials in AAV were elaborated and are presented in this summary document. It was decided to consider vasculitis‐specific issues rather than general issues of trial methodology. The recommendations deal with the following areas related to clinical studies of vasculitis: definitions of disease, activity states, outcome measures, eligibility criteria, trial design including relevant end points, and biomarkers. A number of aspects of trial methodology were deemed important for future research. Conclusions On the basis of expert opinion, recommendations for conducting clinical trials in AAV were formulated. Furthermore, the expert committee identified a strong need for well‐designed research in non‐AAV systemic vasculitides. PMID:17170053

Generation of “Virtual” Control Groups for Single Arm Prostate Cancer Adjuvant Trials

PubMed Central

Koziol, James A.; Chen, Xin; Xia, Xiao-Qin; Wang, Yipeng; Skarecky, Douglas; Sutton, Manuel; Sawyers, Anne; Ruckle, Herbert; Carpenter, Philip M.; Wang-Rodriguez, Jessica; Jiang, Jun; Deng, Mingsen; Pan, Cong; Zhu, Jian-guo; McLaren, Christine E.; Gurley, Michael J.; Lee, Chung; McClelland, Michael; Ahlering, Thomas; Kattan, Michael W.; Mercola, Dan

2014-01-01

It is difficult to construct a control group for trials of adjuvant therapy (Rx) of prostate cancer after radical prostatectomy (RP) due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, … 95% chance of progression free survival (PFS) based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets) whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies. PMID:24465467

Generation of "virtual" control groups for single arm prostate cancer adjuvant trials.

PubMed

Jia, Zhenyu; Lilly, Michael B; Koziol, James A; Chen, Xin; Xia, Xiao-Qin; Wang, Yipeng; Skarecky, Douglas; Sutton, Manuel; Sawyers, Anne; Ruckle, Herbert; Carpenter, Philip M; Wang-Rodriguez, Jessica; Jiang, Jun; Deng, Mingsen; Pan, Cong; Zhu, Jian-Guo; McLaren, Christine E; Gurley, Michael J; Lee, Chung; McClelland, Michael; Ahlering, Thomas; Kattan, Michael W; Mercola, Dan

2014-01-01

It is difficult to construct a control group for trials of adjuvant therapy (Rx) of prostate cancer after radical prostatectomy (RP) due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, … 95% chance of progression free survival (PFS) based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets) whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies.

Systematically convergent basis sets for transition metals. I. All-electron correlation consistent basis sets for the 3d elements Sc-Zn

NASA Astrophysics Data System (ADS)

Balabanov, Nikolai B.; Peterson, Kirk A.

2005-08-01

Sequences of basis sets that systematically converge towards the complete basis set (CBS) limit have been developed for the first-row transition metal elements Sc-Zn. Two families of basis sets, nonrelativistic and Douglas-Kroll-Hess (-DK) relativistic, are presented that range in quality from triple-ζ to quintuple-ζ. Separate sets are developed for the description of valence (3d4s) electron correlation (cc-pVnZ and cc-pVnZ-DK; n =T,Q, 5) and valence plus outer-core (3s3p3d4s) correlation (cc-pwCVnZ and cc-pwCVnZ-DK; n =T,Q, 5), as well as these sets augmented by additional diffuse functions for the description of negative ions and weak interactions (aug-cc-pVnZ and aug-cc-pVnZ-DK). Extensive benchmark calculations at the coupled cluster level of theory are presented for atomic excitation energies, ionization potentials, and electron affinities, as well as molecular calculations on selected hydrides (TiH, MnH, CuH) and other diatomics (TiF, Cu2). In addition to observing systematic convergence towards the CBS limits, both 3s3p electron correlation and scalar relativity are calculated to strongly impact many of the atomic and molecular properties investigated for these first-row transition metal species.

Adapted Behavior Therapy for Persistently Depressed Primary Care Patients: An Open Trial

ERIC Educational Resources Information Center

Uebelacker, Lisa A.; Weisberg, Risa B.; Haggarty, Ryan; Miller, Ivan W.

2009-01-01

Major depressive disorder is commonly treated in primary care settings. Psychotherapy occurring in primary care should take advantage of the unique aspects of the setting and must adapt to the problems and limitations of the setting. In this open trial, the authors used a treatment development model to adapt behavior therapy for primary care…

Gaussian basis sets for use in correlated molecular calculations. XI. Pseudopotential-based and all-electron relativistic basis sets for alkali metal (K-Fr) and alkaline earth (Ca-Ra) elements

NASA Astrophysics Data System (ADS)

Hill, J. Grant; Peterson, Kirk A.

2017-12-01

New correlation consistent basis sets based on pseudopotential (PP) Hamiltonians have been developed from double- to quintuple-zeta quality for the late alkali (K-Fr) and alkaline earth (Ca-Ra) metals. These are accompanied by new all-electron basis sets of double- to quadruple-zeta quality that have been contracted for use with both Douglas-Kroll-Hess (DKH) and eXact 2-Component (X2C) scalar relativistic Hamiltonians. Sets for valence correlation (ms), cc-pVnZ-PP and cc-pVnZ-(DK,DK3/X2C), in addition to outer-core correlation [valence + (m-1)sp], cc-p(w)CVnZ-PP and cc-pwCVnZ-(DK,DK3/X2C), are reported. The -PP sets have been developed for use with small-core PPs [I. S. Lim et al., J. Chem. Phys. 122, 104103 (2005) and I. S. Lim et al., J. Chem. Phys. 124, 034107 (2006)], while the all-electron sets utilized second-order DKH Hamiltonians for 4s and 5s elements and third-order DKH for 6s and 7s. The accuracy of the basis sets is assessed through benchmark calculations at the coupled-cluster level of theory for both atomic and molecular properties. Not surprisingly, it is found that outer-core correlation is vital for accurate calculation of the thermodynamic and spectroscopic properties of diatomic molecules containing these elements.

Recommended Patient-Reported Core Set of Symptoms to Measure in Adult Cancer Treatment Trials

PubMed Central

Mitchell, Sandra A.; Dueck, Amylou C.; Basch, Ethan; Cella, David; Reilly, Carolyn Miller; Minasian, Lori M.; Denicoff, Andrea M.; O’Mara, Ann M.; Fisch, Michael J.; Chauhan, Cynthia; Aaronson, Neil K.; Coens, Corneel; Bruner, Deborah Watkins

2014-01-01

Background The National Cancer Institute’s Symptom Management and Health-Related Quality of Life Steering Committee held a clinical trials planning meeting (September 2011) to identify a core symptom set to be assessed across oncology trials for the purposes of better understanding treatment efficacy and toxicity and to facilitate cross-study comparisons. We report the results of an evidence-synthesis and consensus-building effort that culminated in recommendations for core symptoms to be measured in adult cancer clinical trials that include a patient-reported outcome (PRO). Methods We used a data-driven, consensus-building process. A panel of experts, including patient representatives, conducted a systematic review of the literature (2001–2011) and analyzed six large datasets. Results were reviewed at a multistakeholder meeting, and a final set was derived emphasizing symptom prevalence across diverse cancer populations, impact on health outcomes and quality of life, and attribution to either disease or anticancer treatment. Results We recommend that a core set of 12 symptoms—specifically fatigue, insomnia, pain, anorexia (appetite loss), dyspnea, cognitive problems, anxiety (includes worry), nausea, depression (includes sadness), sensory neuropathy, constipation, and diarrhea—be considered for inclusion in clinical trials where a PRO is measured. Inclusion of symptoms and other patient-reported endpoints should be well justified, hypothesis driven, and meaningful to patients. Conclusions This core set will promote consistent assessment of common and clinically relevant disease- and treatment-related symptoms across cancer trials. As such, it provides a foundation to support data harmonization and continued efforts to enhance measurement of patient-centered outcomes in cancer clinical trials and observational studies. PMID:25006191

Ab initio calculation of reaction energies. III. Basis set dependence of relative energies on the FH2 and H2CO potential energy surfaces

NASA Astrophysics Data System (ADS)

Frisch, Michael J.; Binkley, J. Stephen; Schaefer, Henry F., III

1984-08-01

The relative energies of the stationary points on the FH2 and H2CO nuclear potential energy surfaces relevant to the hydrogen atom abstraction, H2 elimination and 1,2-hydrogen shift reactions have been examined using fourth-order Møller-Plesset perturbation theory and a variety of basis sets. The theoretical absolute zero activation energy for the F+H2→FH+H reaction is in better agreement with experiment than previous theoretical studies, and part of the disagreement between earlier theoretical calculations and experiment is found to result from the use of assumed rather than calculated zero-point vibrational energies. The fourth-order reaction energy for the elimination of hydrogen from formaldehyde is within 2 kcal mol-1 of the experimental value using the largest basis set considered. The qualitative features of the H2CO surface are unchanged by expansion of the basis set beyond the polarized triple-zeta level, but diffuse functions and several sets of polarization functions are found to be necessary for quantitative accuracy in predicted reaction and activation energies. Basis sets and levels of perturbation theory which represent good compromises between computational efficiency and accuracy are recommended.

Adjuvant chemotherapy for soft tissue sarcoma.

PubMed

Casali, Paolo G

2015-01-01

Adjuvant chemotherapy is not standard treatment in soft tissue sarcoma (STS). However, when the risk of relapse is high, it is an option for shared decision making with the patient in conditions of uncertainty. This is because available evidence is conflicting, even if several randomized clinical trials have been performed for 4 decades and also have been pooled into meta-analyses. Indeed, available meta-analyses point to a benefit in the 5% to 10% range in terms of survival and distant relapse rate. Some local benefit also was suggested by some trials. Placing chemotherapy in the preoperative setting may help gain a local advantage in terms of the quality of surgical margins or decreased sequelae. This may be done within a personalized approach according to the clinical presentation. Attempts to personalize treatment on the basis of the variegated pathology and molecular biology of STS subgroups are ongoing as well, according to what is done in the medical treatment of advanced STS. Thus, decision making for adjuvant and neoadjuvant indications deserves personalization in clinical research and in clinical practice, taking profit from all multidisciplinary clinical skills available at a sarcoma reference center, though with a degree of subjectivity because of the limitations of available evidence.

Power and money in cluster randomized trials: when is it worth measuring a covariate?

PubMed

Moerbeek, Mirjam

2006-08-15

The power to detect a treatment effect in cluster randomized trials can be increased by increasing the number of clusters. An alternative is to include covariates into the regression model that relates treatment condition to outcome. In this paper, formulae are derived in order to evaluate both strategies on basis of their costs. It is shown that the strategy that uses covariates is more cost-efficient in detecting a treatment effect when the costs to measure these covariates are small and the correlation between the covariates and outcome is sufficiently large. The minimum required correlation depends on the cluster size, and the costs to recruit a cluster and to measure the covariate, relative to the costs to recruit a person. Measuring a covariate that varies at the person level only is recommended when cluster sizes are small and the costs to recruit and measure a cluster are large. Measuring a cluster level covariate is recommended when cluster sizes are large and the costs to recruit and measure a cluster are small. An illustrative example shows the use of the formulae in a practical setting. Copyright 2006 John Wiley & Sons, Ltd.

Implementation of an open adoption research data management system for clinical studies.

PubMed

Müller, Jan; Heiss, Kirsten Ingmar; Oberhoffer, Renate

2017-07-06

Research institutions need to manage multiple studies with individual data sets, processing rules and different permissions. So far, there is no standard technology that provides an easy to use environment to create databases and user interfaces for clinical trials or research studies. Therefore various software solutions are being used-from custom software, explicitly designed for a specific study, to cost intensive commercial Clinical Trial Management Systems (CTMS) up to very basic approaches with self-designed Microsoft ® databases. The technology applied to conduct those studies varies tremendously from study to study, making it difficult to evaluate data across various studies (meta-analysis) and keeping a defined level of quality in database design, data processing, displaying and exporting. Furthermore, the systems being used to collect study data are often operated redundantly to systems used in patient care. As a consequence the data collection in studies is inefficient and data quality may suffer from unsynchronized datasets, non-normalized database scenarios and manually executed data transfers. With OpenCampus Research we implemented an open adoption software (OAS) solution on an open source basis, which provides a standard environment for state-of-the-art research database management at low cost.

Use of Dried Capillary Blood Sampling for Islet Autoantibody Screening in Relatives: A Feasibility Study.

PubMed

Bingley, Polly J; Rafkin, Lisa E; Matheson, Della; Steck, Andrea K; Yu, Liping; Henderson, Courtney; Beam, Craig A; Boulware, David C

2015-12-01

Islet autoantibody testing provides the basis for assessment of risk of progression to type 1 diabetes. We set out to determine the feasibility and acceptability of dried capillary blood spot-based screening to identify islet autoantibody-positive relatives potentially eligible for inclusion in prevention trials. Dried blood spot (DBS) and venous samples were collected from 229 relatives participating in the TrialNet Pathway to Prevention Study. Both samples were tested for glutamic acid decarboxylase, islet antigen 2, and zinc transporter 8 autoantibodies, and venous samples were additionally tested for insulin autoantibodies and islet cell antibodies. We defined multiple autoantibody positive as two or more autoantibodies in venous serum and DBS screen positive if one or more autoantibodies were detected. Participant questionnaires compared the sample collection methods. Of 44 relatives who were multiple autoantibody positive in venous samples, 42 (95.5%) were DBS screen positive, and DBS accurately detected 145 of 147 autoantibody-negative relatives (98.6%). Capillary blood sampling was perceived as more painful than venous blood draw, but 60% of participants would prefer initial screening using home fingerstick with clinic visits only required if autoantibodies were found. Capillary blood sampling could facilitate screening for type 1 diabetes prevention studies.

Decoding spoken words using local field potentials recorded from the cortical surface

NASA Astrophysics Data System (ADS)

Kellis, Spencer; Miller, Kai; Thomson, Kyle; Brown, Richard; House, Paul; Greger, Bradley

2010-10-01

Pathological conditions such as amyotrophic lateral sclerosis or damage to the brainstem can leave patients severely paralyzed but fully aware, in a condition known as 'locked-in syndrome'. Communication in this state is often reduced to selecting individual letters or words by arduous residual movements. More intuitive and rapid communication may be restored by directly interfacing with language areas of the cerebral cortex. We used a grid of closely spaced, nonpenetrating micro-electrodes to record local field potentials (LFPs) from the surface of face motor cortex and Wernicke's area. From these LFPs we were successful in classifying a small set of words on a trial-by-trial basis at levels well above chance. We found that the pattern of electrodes with the highest accuracy changed for each word, which supports the idea that closely spaced micro-electrodes are capable of capturing neural signals from independent neural processing assemblies. These results further support using cortical surface potentials (electrocorticography) in brain-computer interfaces. These results also show that LFPs recorded from the cortical surface (micro-electrocorticography) of language areas can be used to classify speech-related cortical rhythms and potentially restore communication to locked-in patients.

Healing of donor site in bone-tendon-bone ACL reconstruction accelerated with plasma rich in growth factors: a randomized clinical trial.

PubMed

Seijas, Roberto; Rius, Marta; Ares, Oscar; García-Balletbó, Montserrat; Serra, Iván; Cugat, Ramón

2015-04-01

To determine whether the use of plasma rich in growth factors accelerates healing of the donor site in bone-tendon-bone anterior cruciate ligament (ACL) reconstruction (patellar graft). The use of the patellar graft presents post-operative problems such as anterior knee pain, which limits its use and leads to preference being taken for alternative grafts. A double-blind, randomized, clinical trial was performed comparing two groups of patients who underwent ACL reconstruction using patellar tendon graft and comparing the use of plasma rich in growth factors at the donor site after graft harvest in terms of local regeneration by ultrasound assessment. The plasma rich in growth factors group shows earlier donor site regeneration in comparison with the control group (2 months earlier), with significant differences in the first 4 months of the follow-up. The application of plasma rich in growth factors shows accelerated tissue regeneration processes with respect to the control group. This fact, together with the previously published with similar conclusions, can create a knowledge basis in order to set out new recovery guidelines following ACL reconstruction. Therapeutic study, Level I.

Calculations of molecular multipole electric moments of a series of exo-insaturated four-membered heterocycles, Y = CCH2CH2X

NASA Astrophysics Data System (ADS)

Romero, Angel H.

2017-10-01

The influence of ring puckering angle on the multipole moments of sixteen four-membered heterocycles (1-16) was theoretically estimated using MP2 and different DFTs in combination with the 6-31+G(d,p) basis set. To obtain an accurate evaluation, CCSD/cc-pVDZ level and, the MP2 and PBE1PBE methods in combination with the aug-cc-pVDZ and aug-cc-pVTZ basis sets were performed on the planar geometries of 1-16. In general, the DFT and MP2 approaches provided an identical dependence of the electrical properties with the puckering angle for 1-16. Quantitatively, the quality of the level of theory and basis sets affects significant the predictions of the multipole moments, in particular for the heterocycles containing C=O and C=S bonds. Convergence basis sets within the MP2 and PBE1PBE approximations are reached in the dipole moment calculations when the aug-cc-pVTZ basis set is used, while the quadrupole and octupole moment computations require a larger basis set than aug-cc-pVTZ. On the other hand, the multipole moments showed a strong dependence with the molecular geometry and the nature of the carbon-heteroatom bonds. Specifically, the C-X bond determines the behavior of the μ(ϕ), θ(ϕ) and Ώ(ϕ) functions, while the C=Y bond plays an important role in the magnitude of the studied properties.

A Poisson approach to the validation of failure time surrogate endpoints in individual patient data meta-analyses.

PubMed

Rotolo, Federico; Paoletti, Xavier; Burzykowski, Tomasz; Buyse, Marc; Michiels, Stefan

2017-01-01

Surrogate endpoints are often used in clinical trials instead of well-established hard endpoints for practical convenience. The meta-analytic approach relies on two measures of surrogacy: one at the individual level and one at the trial level. In the survival data setting, a two-step model based on copulas is commonly used. We present a new approach which employs a bivariate survival model with an individual random effect shared between the two endpoints and correlated treatment-by-trial interactions. We fit this model using auxiliary mixed Poisson models. We study via simulations the operating characteristics of this mixed Poisson approach as compared to the two-step copula approach. We illustrate the application of the methods on two individual patient data meta-analyses in gastric cancer, in the advanced setting (4069 patients from 20 randomized trials) and in the adjuvant setting (3288 patients from 14 randomized trials).

Building clinical trial capacity to develop a new treatment for multidrug-resistant tuberculosis.

PubMed

Tupasi, Thelma; Gupta, Rajesh; Danilovits, Manfred; Cirule, Andra; Sanchez-Garavito, Epifanio; Xiao, Heping; Cabrera-Rivero, Jose L; Vargas-Vasquez, Dante E; Gao, Mengqiu; Awad, Mohamed; Gentry, Leesa M; Geiter, Lawrence J; Wells, Charles D

2016-02-01

New drugs for infectious diseases often need to be evaluated in low-resource settings. While people working in such settings often provide high-quality care and perform operational research activities, they generally have less experience in conducting clinical trials designed for drug approval by stringent regulatory authorities. We carried out a capacity-building programme during a multi-centre randomized controlled trial of delamanid, a new drug for the treatment of multidrug-resistant tuberculosis. The programme included: (i) site identification and needs assessment; (ii) achieving International Conference on Harmonization - Good Clinical Practice (ICH-GCP) standards; (iii) establishing trial management; and (iv) increasing knowledge of global and local regulatory issues. Trials were conducted at 17 sites in nine countries (China, Egypt, Estonia, Japan, Latvia, Peru, the Philippines, the Republic of Korea and the United States of America). Eight of the 10 sites in low-resource settings had no experience in conducting the requisite clinical trials. Extensive capacity-building was done in all 10 sites. The programme resulted in improved local capacity in key areas such as trial design, data safety and monitoring, trial conduct and laboratory services. Clinical trials designed to generate data for regulatory approval require additional efforts beyond traditional research-capacity strengthening. Such capacity-building approaches provide an opportunity for product development partnerships to improve health systems beyond the direct conduct of the specific trial.

The Relationship between Zinc Intake and Serum/Plasma Zinc Concentration in Children: A Systematic Review and Dose-Response Meta-Analysis

PubMed Central

Moran, Victoria Hall; Stammers, Anna-Louise; Medina, Marisol Warthon; Patel, Sujata; Dykes, Fiona; Souverein, Olga W.; Dullemeijer, Carla; Pérez-Rodrigo, Carmen; Serra-Majem, Lluis; Nissensohn, Mariela; Lowe, Nicola M.

2012-01-01

Recommendations for zinc intake during childhood vary widely across Europe. The EURRECA project attempts to consolidate the basis for the definition of micronutrient requirements, taking into account relationships among intake, status and health outcomes, in order to harmonise these recommendations. Data on zinc intake and biomarkers of zinc status reported in randomised controlled trials (RCTs) can provide estimates of dose-response relationships which may be used for underpinning zinc reference values. This systematic review included all RCTs of apparently healthy children aged 1–17 years published by February 2010 which provided data on zinc intake and biomarkers of zinc status. An intake-status regression coefficient () was calculated for each individual study and calculated the overall pooled and SE () using random effects meta-analysis on a double log scale. The pooled dose-response relationship between zinc intake and zinc status indicated that a doubling of the zinc intake increased the serum/plasma zinc status by 9%. This evidence can be utilised, together with currently used balance studies and repletion/depletion studies, when setting zinc recommendations as a basis for nutrition policies. PMID:23016120

Delivering an Optimised Behavioural Intervention (OBI) to people with low back pain with high psychological risk; results and lessons learnt from a feasibility randomised controlled trial of Contextual Cognitive Behavioural Therapy (CCBT) vs. Physiotherapy.

PubMed

Pincus, Tamar; Anwar, Shamaila; McCracken, Lance M; McGregor, Alison; Graham, Liz; Collinson, Michelle; McBeth, John; Watson, Paul; Morley, Stephen; Henderson, Juliet; Farrin, Amanda J

2015-06-16

Low Back Pain (LBP) remains a common and costly problem. Psychological obstacles to recovery have been identified, but psychological and behavioural interventions have produced only moderate improvements. Reviews of trials have suggested that the interventions lack clear theoretical basis, are often compromised by low dose, lack of fidelity, and delivery by non-experts. In addition, interventions do not directly target known risk mechanisms. We identified a theory driven intervention (Contexual Cognitive Behavioural Therapy, CCBT) that directly targets an evidence-based risk mechanism (avoidance and ensured dose and delivery were optimised. This feasibility study was designed to test the credibility and acceptability of optimised CCBT against physiotherapy for avoidant LBP patients, and to test recruitment, delivery of the intervention and response rates prior to moving to a full definitive trial. A randomised controlled feasibility trial with patients randomised to receive CCBT or physiotherapy. CCBT was delivered by trained supervised psychologists on a one to one basis and comprised up to 8 one-hour sessions. Physiotherapy comprised back to fitness group exercises with at least 60 % of content exercise-based. Patients were eligible to take part if they had back pain for more than 3 months, and scored above a threshold indicating fear avoidance, catastrophic beliefs and distress. 89 patients were recruited. Uptake rates were above those predicted. Scores for credibility and acceptability of the interventions met the set criteria. Response rates at three and six months fell short of the 75 % target. Problems associated with poor response rates were identified and successfully resolved, rates increased to 77 % at 3 months, and 68 % at 6 months. Independent ratings of treatment sessions indicated that CCBT was delivered to fidelity. Numbers were too small for formal analysis. Although average scores for acceptance were higher in the CCBT group than in the group attending physiotherapy (increase of 7.9 versus 5.1) and change in disability and pain from baseline to 6 months were greater in the CCBT group than in the physiotherapy group, these findings should be interpreted with caution. CCBT is a credible and acceptable intervention for LBP patients who exhibit psychological obstacles to recovery. ISRCTN43733490 , registered 15/12/2010.

Antiviral therapeutics for the treatment of Ebola virus infection.

PubMed

Cardile, Anthony P; Downey, Lydia G; Wiseman, Perry D; Warren, Travis K; Bavari, Sina

2016-10-01

There have been significant developments in Ebola virus therapeutics. While the efficacy of several products was evaluated in the recent West Africa outbreak, a licensed treatment for EBOV disease remains elusive. Factors that negatively impacted the execution of clinical trials included an overall lack of world readiness to conduct clinical trials in an outbreak setting, ethical concerns limiting implementation of the randomized controlled trials in an outbreak setting, and a decline in case numbers by the time resources were mobilized to conduct clinical trials. We summarize relevant therapeutics that underwent clinical trials during the West Africa outbreak and highlight promising candidates under advanced development. Published by Elsevier Ltd.

Straightening the Hierarchical Staircase for Basis Set Extrapolations: A Low-Cost Approach to High-Accuracy Computational Chemistry

NASA Astrophysics Data System (ADS)

Varandas, António J. C.

2018-04-01

Because the one-electron basis set limit is difficult to reach in correlated post-Hartree-Fock ab initio calculations, the low-cost route of using methods that extrapolate to the estimated basis set limit attracts immediate interest. The situation is somewhat more satisfactory at the Hartree-Fock level because numerical calculation of the energy is often affordable at nearly converged basis set levels. Still, extrapolation schemes for the Hartree-Fock energy are addressed here, although the focus is on the more slowly convergent and computationally demanding correlation energy. Because they are frequently based on the gold-standard coupled-cluster theory with single, double, and perturbative triple excitations [CCSD(T)], correlated calculations are often affordable only with the smallest basis sets, and hence single-level extrapolations from one raw energy could attain maximum usefulness. This possibility is examined. Whenever possible, this review uses raw data from second-order Møller-Plesset perturbation theory, as well as CCSD, CCSD(T), and multireference configuration interaction methods. Inescapably, the emphasis is on work done by the author's research group. Certain issues in need of further research or review are pinpointed.

Reconciling the influence of task-set switching and motor inhibition processes on stop signal after-effects.

PubMed

Anguera, Joaquin A; Lyman, Kyle; Zanto, Theodore P; Bollinger, Jacob; Gazzaley, Adam

2013-01-01

Executive response functions can be affected by preceding events, even if they are no longer associated with the current task at hand. For example, studies utilizing the stop signal task have reported slower response times to "GO" stimuli when the preceding trial involved the presentation of a "STOP" signal. However, the neural mechanisms that underlie this behavioral after-effect are unclear. To address this, behavioral and electroencephalography (EEG) measures were examined in 18 young adults (18-30 years) on "GO" trials following a previously "Successful Inhibition" trial (pSI), a previously "Failed Inhibition" trial (pFI), and a previous "GO" trial (pGO). Like previous research, slower response times were observed during both pSI and pFI trials (i.e., "GO" trials that were preceded by a successful and unsuccessful inhibition trial, respectively) compared to pGO trials (i.e., "GO" trials that were preceded by another "GO" trial). Interestingly, response time slowing was greater during pSI trials compared to pFI trials, suggesting executive control is influenced by both task set switching and persisting motor inhibition processes. Follow-up behavioral analyses indicated that these effects resulted from between-trial control adjustments rather than repetition priming effects. Analyses of inter-electrode coherence (IEC) and inter-trial coherence (ITC) indicated that both pSI and pFI trials showed greater phase synchrony during the inter-trial interval compared to pGO trials. Unlike the IEC findings, differential ITC was present within the beta and alpha frequency bands in line with the observed behavior (pSI > pFI > pGO), suggestive of more consistent phase synchrony involving motor inhibition processes during the ITI at a regional level. These findings suggest that between-trial control adjustments involved with task-set switching and motor inhibition processes influence subsequent performance, providing new insights into the dynamic nature of executive control.

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

McKemmish, Laura K., E-mail: laura.mckemmish@gmail.com; Research School of Chemistry, Australian National University, Canberra

Algorithms for the efficient calculation of two-electron integrals in the newly developed mixed ramp-Gaussian basis sets are presented, alongside a Fortran90 implementation of these algorithms, RAMPITUP. These new basis sets have significant potential to (1) give some speed-up (estimated at up to 20% for large molecules in fully optimised code) to general-purpose Hartree-Fock (HF) and density functional theory quantum chemistry calculations, replacing all-Gaussian basis sets, and (2) give very large speed-ups for calculations of core-dependent properties, such as electron density at the nucleus, NMR parameters, relativistic corrections, and total energies, replacing the current use of Slater basis functions or verymore » large specialised all-Gaussian basis sets for these purposes. This initial implementation already demonstrates roughly 10% speed-ups in HF/R-31G calculations compared to HF/6-31G calculations for large linear molecules, demonstrating the promise of this methodology, particularly for the second application. As well as the reduction in the total primitive number in R-31G compared to 6-31G, this timing advantage can be attributed to the significant reduction in the number of mathematically complex intermediate integrals after modelling each ramp-Gaussian basis-function-pair as a sum of ramps on a single atomic centre.« less

Evaluating the design and reporting of pragmatic trials in osteoarthritis research.

PubMed

Ali, Shabana Amanda; Kloseck, Marita; Lee, Karen; Walsh, Kathleen Ellen; MacDermid, Joy C; Fitzsimmons, Deborah

2018-01-01

Among the challenges in health research is translating interventions from controlled experimental settings to clinical and community settings where chronic disease is managed daily. Pragmatic trials offer a method for testing interventions in real-world settings but are seldom used in OA research. The aim of this study was to evaluate the literature on pragmatic trials in OA research up to August 2016 in order to identify strengths and weaknesses in the design and reporting of these trials. We used established guidelines to assess the degree to which 61 OA studies complied with pragmatic trial design and reporting. We assessed design according to the pragmatic-explanatory continuum indicator summary and reporting according to the pragmatic trials extension of the CONsolidated Standards of Reporting Trials guidelines. None of the pragmatic trials met all 11 criteria evaluated and most of the trials met between 5 and 8 of the criteria. Criteria most often unmet pertained to practitioner expertise (by requiring specialists) and criteria most often met pertained to primary outcome analysis (by using intention-to-treat analysis). Our results suggest a lack of highly pragmatic trials in OA research. We identify this as a point of opportunity to improve research translation, since optimizing the design and reporting of pragmatic trials can facilitate implementation of evidence-based interventions for OA care. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Quantum Mechanical Calculations of Monoxides of Silicon Carbide Molecules

DTIC Science & Technology

2003-03-01

Data for CO Final Energy Charge Mult Basis Set (hart) EA (eV) ZPE (hart) EA (eV) w/ ZPE 0 1 DVZ -112.6850703739 2.02121 -1 2 DVZ...Energy Charge Mult Basis Set (hart) EA (eV) ZPE (hart) EA (eV) w/ ZPE 0 1 DVZ -363.7341927429 0.617643 -1 2 DVZ -363.7114852831 0 3 DVZ...Input Geometry Output Geometry Basis Set Final Energy (hart) EA (eV) ZPE (hart) EA (eV) w/ ZPE -1 2 O-C-Si Linear O-C-Si Linear DZV -401.5363

Relativistic well-tempered Gaussian basis sets for helium through mercury. Breit interaction included

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

Okada, S.; Shinada, M.; Matsuoka, O.

1990-10-01

A systematic calculation of new relativistic Gaussian basis sets is reported. The new basis sets are similar to the previously reported ones (J. Chem. Phys. {bold 91}, 4193 (1989)), but, in the calculation, the Breit interaction has been explicitly included besides the Dirac--Coulomb Hamiltonian. They have been adopted for the calculation of the self-consistent field effect on the Breit interaction energies and are expected to be useful for the studies on higher-order effects such as the electron correlations and other quantum electrodynamical effects.

Parallel Douglas-Kroll Energy and Gradients in NWChem. Estimating Scalar Relativistic Effects Using Douglas-Kroll Contracted Basis Sets.

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

De Jong, Wibe A.; Harrison, Robert J.; Dixon, David A.

A parallel implementation of the spin-free one-electron Douglas-Kroll(-Hess) Hamiltonian (DKH) in NWChem is discussed. An efficient and accurate method to calculate DKH gradients is introduced. It is shown that the use of standard (non-relativistic) contracted basis set can produce erroneous results for elements beyond the first row elements. The generation of DKH contracted cc-pVXZ (X = D, T, Q, 5) basis sets for H, He, B - Ne, Al - Ar, and Ga - Br will be discussed.

Neratinib for the treatment of HER2-positive early stage breast cancer.

PubMed

Echavarria, Isabel; López-Tarruella, Sara; Márquez-Rodas, Iván; Jerez, Yolanda; Martin, Miguel

2017-08-01

Despite the advances in the treatment of HER2-positive breast cancer, resistance to actual chemotherapeutic regimens eventually occurs. Neratinib, an orally available pan-inhibitor of the ERBB family, represents an interesting new option for early-stage HER2-positive breast cancer. Areas covered: In this article, the development of neratinib, with a special focus on its potential value in the treatment of early-stage HER2-positive breast cancer, has been reviewed. For this purpose, a literature search was conducted, including preclinical studies, early-phase trials in advanced cancer with neratinib in monotherapy and in combination, and phase II and large phase III trials in the early setting. Management of neratinib-induced toxicity, future perspectives for the drug, and ongoing trials are also discussed in this review. Expert commentary: Neratinib is emerging as a promising oral drug for the treatment of HER2-positive breast cancer. Although FDA and EMA approval is derived from the extended adjuvant treatment, this setting may not be the ideal scenario to obtain the beneficial effects of neratinib. Confirmatory data in the neoadjuvant setting and subgroup analysis from the ExTENET trial might bring some light into the best setting for neratinib therapy. Data from confirmatory trials in the metastatic setting are also required.

On the Usage of Locally Dense Basis Sets in the Calculation of NMR Indirect Nuclear Spin-Spin Coupling Constants

NASA Astrophysics Data System (ADS)

Sanchez, Marina; Provasi, Patricio F.; Aucar, Gustavo A.; Sauer, Stephan P. A.

Locally dense basis sets (

A complex breastfeeding promotion and support intervention in a developing country: study protocol for a randomized clinical trial.

PubMed

Nabulsi, Mona; Hamadeh, Haya; Tamim, Hani; Kabakian, Tamar; Charafeddine, Lama; Yehya, Nadine; Sinno, Durriyah; Sidani, Saadieh

2014-01-15

Breastfeeding has countless benefits to mothers, children and community at large, especially in developing countries. Studies from Lebanon report disappointingly low breastfeeding exclusivity and continuation rates. Evidence reveals that antenatal breastfeeding education, professional lactation support, and peer lay support are individually effective at increasing breastfeeding duration and exclusivity, particularly in low-income settings. Given the complex nature of the breastfeeding ecosystem and its barriers in Lebanon, we hypothesize that a complex breastfeeding support intervention, which is centered on the three components mentioned above, would significantly increase breastfeeding rates. A multi-center randomized controlled trial. 443 healthy pregnant women in their first trimester will be randomized to control or intervention group. A "prenatal/postnatal" professional and peer breastfeeding support package continuing till 6 months postpartum, guided by the Social Network and Social Support Theory. Control group will receive standard prenatal and postnatal care. Mothers will be followed up from early pregnancy till five years after delivery. Total and exclusive breastfeeding rates, quality of life at 1, 3 and 6 months postpartum, maternal breastfeeding knowledge and attitudes at 6 months postpartum, maternal exclusive breastfeeding rates of future infants up to five years from baseline, cost-benefit and cost-effectiveness analyses of the intervention. Descriptive and regression analysis will be conducted under the intention to treat basis using the most recent version of SPSS. Exclusive breastfeeding is a cost-effective public health measure that has a significant impact on infant morbidity and mortality. In a country with limited healthcare resources like Lebanon, developing an effective breastfeeding promotion and support intervention that is easily replicated across various settings becomes a priority. If positive, the results of this study would provide a generalizable model to bolster breastfeeding promotion efforts and contribute to improved child health in Lebanon and the Middle East and North Africa (MENA) region. Current Controlled Trials ISRCTN17875591.

Near Hartree-Fock quality GTO basis sets for the first- and third-row atoms

NASA Technical Reports Server (NTRS)

Partridge, Harry

1989-01-01

Energy-optimized Gaussian-type-orbital (GTO) basis sets of accuracy approaching that of numerical Hartree-Fock computations are compiled for the elements of the first and third rows of the periodic table. The methods employed in calculating the sets are explained; the applicability of the sets to electronic-structure calculations is discussed; and the results are presented in tables and briefly characterized.

Computational tests of quantum chemical models for excited and ionized states of molecules with phosphorus and sulfur atoms.

PubMed

Hahn, David K; RaghuVeer, Krishans; Ortiz, J V

2014-05-15

Time-dependent density functional theory (TD-DFT) and electron propagator theory (EPT) are used to calculate the electronic transition energies and ionization energies, respectively, of species containing phosphorus or sulfur. The accuracy of TD-DFT and EPT, in conjunction with various basis sets, is assessed with data from gas-phase spectroscopy. TD-DFT is tested using 11 prominent exchange-correlation functionals on a set of 37 vertical and 19 adiabatic transitions. For vertical transitions, TD-CAM-B3LYP calculations performed with the MG3S basis set are lowest in overall error, having a mean absolute deviation from experiment of 0.22 eV, or 0.23 eV over valence transitions and 0.21 eV over Rydberg transitions. Using a larger basis set, aug-pc3, improves accuracy over the valence transitions via hybrid functionals, but improved accuracy over the Rydberg transitions is only obtained via the BMK functional. For adiabatic transitions, all hybrid functionals paired with the MG3S basis set perform well, and B98 is best, with a mean absolute deviation from experiment of 0.09 eV. The testing of EPT used the Outer Valence Green's Function (OVGF) approximation and the Partial Third Order (P3) approximation on 37 vertical first ionization energies. It is found that OVGF outperforms P3 when basis sets of at least triple-ζ quality in the polarization functions are used. The largest basis set used in this study, aug-pc3, obtained the best mean absolute error from both methods -0.08 eV for OVGF and 0.18 eV for P3. The OVGF/6-31+G(2df,p) level of theory is particularly cost-effective, yielding a mean absolute error of 0.11 eV.

A new account of the effect of probability on task switching: ERP evidence following the manipulation of switch probability, cue informativeness and predictability

PubMed Central

Nessler, Doreen; Friedman, David; Johnson, Ray

2012-01-01

This task-switching ERP study of 16 young participants investigated whether increased RT slowing on stay trials and faster RTs on switch trials for frequent than infrequent switching are explained by an activation or preparation account. The activation account proposes that task sets are maintained at a higher baseline activation level for frequent switching, necessitating increased task-set updating, as reflected by a larger and/or longer lasting early parietal positivity. The preparation account assumes advance (pre-cue) switch preparation (i.e., task-set reconfiguration), preceding stay and switch trials for frequent switching, as reflected by pre-cue and post-cue late parietal positivities. By and large, the data support the activation account. However, we also found increased, pre-cue task-set updating on frequent stay trials and pre-cue, task-set reconfiguration prior to predictable, frequent switches. These results lead us to propose an extended activation account to explain the effects of switch probability on the executive processes underlying task-switching behavior. PMID:22820040

No need for external orthogonality in subsystem density-functional theory.

PubMed

Unsleber, Jan P; Neugebauer, Johannes; Jacob, Christoph R

2016-08-03

Recent reports on the necessity of using externally orthogonal orbitals in subsystem density-functional theory (SDFT) [Annu. Rep. Comput. Chem., 8, 2012, 53; J. Phys. Chem. A, 118, 2014, 9182] are re-investigated. We show that in the basis-set limit, supermolecular Kohn-Sham-DFT (KS-DFT) densities can exactly be represented as a sum of subsystem densities, even if the subsystem orbitals are not externally orthogonal. This is illustrated using both an analytical example and in basis-set free numerical calculations for an atomic test case. We further show that even with finite basis sets, SDFT calculations using accurate reconstructed potentials can closely approach the supermolecular KS-DFT density, and that the deviations between SDFT and KS-DFT decrease as the basis-set limit is approached. Our results demonstrate that formally, there is no need to enforce external orthogonality in SDFT, even though this might be a useful strategy when developing projection-based DFT embedding schemes.

Open-ended recursive calculation of single residues of response functions for perturbation-dependent basis sets.

PubMed

Friese, Daniel H; Ringholm, Magnus; Gao, Bin; Ruud, Kenneth

2015-10-13

We present theory, implementation, and applications of a recursive scheme for the calculation of single residues of response functions that can treat perturbations that affect the basis set. This scheme enables the calculation of nonlinear light absorption properties to arbitrary order for other perturbations than an electric field. We apply this scheme for the first treatment of two-photon circular dichroism (TPCD) using London orbitals at the Hartree-Fock level of theory. In general, TPCD calculations suffer from the problem of origin dependence, which has so far been solved by using the velocity gauge for the electric dipole operator. This work now enables comparison of results from London orbital and velocity gauge based TPCD calculations. We find that the results from the two approaches both exhibit strong basis set dependence but that they are very similar with respect to their basis set convergence.

Core-core and core-valence correlation

NASA Technical Reports Server (NTRS)

Bauschlicher, Charles W., Jr.; Langhoff, Stephen R.; Taylor, Peter R.

1988-01-01

The effect of (1s) core correlation on properties and energy separations was analyzed using full configuration-interaction (FCI) calculations. The Be 1 S - 1 P, the C 3 P - 5 S and CH+ 1 Sigma + or - 1 Pi separations, and CH+ spectroscopic constants, dipole moment and 1 Sigma + - 1 Pi transition dipole moment were studied. The results of the FCI calculations are compared to those obtained using approximate methods. In addition, the generation of atomic natural orbital (ANO) basis sets, as a method for contracting a primitive basis set for both valence and core correlation, is discussed. When both core-core and core-valence correlation are included in the calculation, no suitable truncated CI approach consistently reproduces the FCI, and contraction of the basis set is very difficult. If the (nearly constant) core-core correlation is eliminated, and only the core-valence correlation is included, CASSCF/MRCI approached reproduce the FCI results and basis set contraction is significantly easier.

Costs of care in a mild-to-moderate Alzheimer clinical trial sample: key resources and their determinants.

PubMed

Gustavsson, Anders; Cattelin, Francoise; Jönsson, Linus

2011-07-01

Costs of care are frequently included as secondary endpoint in Alzheimer clinical trials because payers demand evidence of the budgetary effects of novel therapies. Future clinical trial protocols can be optimized on the basis of the currently available data, including what are the key resources and how are they correlated to disease severity measures. Primary patient-level data from two 18 months clinical trials of a putative disease modifier in mild-to-moderate Alzheimer's disease (n = 2,744) were analyzed to identify key components of costs of care and their determinants in a clinical trial setting. Costs of care were assessed with the resource utilization in dementia Lite (RUD) instrument, which includes patient accommodation, informal care, community care, and hospitalizations. The contribution of each component to total costs of care and their correlation with one another and key disease severity measures (Alzheimer's Disease Assessment Scale--Cognitive Subscale, Mini-Mental State Examination, Clinical Dementia Rating-Sum of Boxes, Alzheimer's Disease Cooperative Study--Activities of Daily Living Inventory, and Neuropsychiatric Inventory Questionnaire) was explored. Informal care constituted 82% to 86% of the total costs of care over the 18-months trial and community care services and patient accommodation contributed 6% to 8% each. Informal care was positively correlated with hospitalizations but negatively to patient accommodation, indicating that these services are supplements. Informal care also had the strongest pair-wise correlation with key disease severity measures, suggesting a higher chance of identifying a treatment effect on this component. ADL-ability (Alzheimer's Disease Cooperative Study--Activities of Daily Living Inventory) was the strongest predictor of costs of care of all disease severity measures. Informal care is the most important component of costs of care in a mild-to-moderate Alzheimer clinical trial sample, and it is primarily driven by the ADL-ability of the patient. Investigators should focus on the assessment of this economic endpoint because a significant treatment effect on this resource is likely to also affect total costs of care. Copyright © 2011 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Comparing the cost-effectiveness of rituximab maintenance and radioimmunotherapy consolidation versus observation following first-line therapy in patients with follicular lymphoma.

PubMed

Chen, Qiushi; Ayer, Turgay; Nastoupil, Loretta J; Rose, Adam C; Flowers, Christopher R

2015-03-01

Phase 3 randomized trials have shown that maintenance rituximab (MR) therapy or radioimmunotherapy (RIT) consolidation following frontline therapy can improve progression-free survival for patients with follicular lymphoma (FL), but the cost-effectiveness of these approaches with respect to observation has not been examined using a common modeling framework. To evaluate and compare the economic impact of MR and RIT consolidation versus observation, respectively, following the first-line induction therapy for patients with advanced-stage FL. We developed Markov models to estimate patients' lifetime costs, quality-adjusted life-years (QALYs), and life-years (LYs) after MR, RIT, and observation following frontline FL treatment from the US payer's perspective. Progression risks, adverse event probabilities, costs, and utilities were estimated from clinical data of Primary RItuximab and MAintenance (PRIMA) trial, Eastern Cooperative Oncology Group (ECOG) trial (for MR), and First-line Indolent Trial (for RIT) and the published literature. We evaluated the incremental cost-effectiveness ratio for direct comparisons between MR/RIT and observation. Model robustness was addressed by one-way and probabilistic sensitivity analyses. Compared with observation, MR provided an additional 1.089 QALYs (1.099 LYs) and 1.399 QALYs (1.391 LYs) on the basis of the PRIMA trial and the ECOG trial, respectively, and RIT provided an additional 1.026 QALYs (1.034 LYs). The incremental cost per QALY gained was $40,335 (PRIMA) or $37,412 (ECOG) for MR and $40,851 for RIT. MR and RIT had comparable incremental QALYs before first progression, whereas RIT had higher incremental costs of adverse events due to higher incidences of cytopenias. MR and RIT following frontline FL therapy demonstrated favorable and similar cost-effectiveness profiles. The model results should be interpreted within the specific clinical settings of each trial. Selection of MR, RIT, or observation should be based on patient characteristics and expected trade-offs for these alternatives. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

When enough is enough: how the decision was made to stop the FEAST trial: data and safety monitoring in an African trial of Fluid Expansion As Supportive Therapy (FEAST) for critically ill children

PubMed Central

2013-01-01

In resource-rich countries, bolus fluid expansion is routinely used for the treatment of poor perfusion and shock, but is less commonly used in many African settings. Controversial results from the recently completed FEAST (Fluid Expansion As Supportive Therapy) trial in African children have raised questions about the use of intravenous bolus fluid for the treatment of shock. Prior to the start of the trial, the Independent data monitoring committee (IDMC) developed stopping rules for the proof of benefit that bolus fluid resuscitation would bring. Although careful safety monitoring was put in place, there was less expectation that bolus fluid expansion would be harmful and differential stopping rules for harm were not formulated. In July 2010, two protocol amendments were agreed to increase the sample size from 2,880 to 3,600 children, and to increase bolus fluid administration. There was a non-significant trend against bolus treatment, but although the implications were discussed, the IDMC did not comment on the results, or on the amendments, in order to avoid inadvertent partial unblinding of the study. In January 2011, the trial was stopped for futility, as the combined intervention arms had significantly higher mortality (relative risk 1.46, 95% CI 1.13 to 1.90, P = 0.004) than the control arm. The stopping rule for proof of benefit was not achieved, and the IDMC stopped the trial with a lower level of significance (P = 0.01) due to futility and an increased risk of mortality from bolus fluid expansion in children enrolled in the trial. The basis for this decision was that the local standard of care was not to use bolus fluid for the care of children with shock in these African countries, and this was a different standard of care to that used in the UK. These decisions emphasize two important principles: firstly, the IDMC should avoid inadvertent unblinding of the trial by commenting on amendments, and secondly, when considering stopping a trial, the IDMC should be guided by the local standard of care rather than standards of care in other parts of the world. PMID:23531379

When enough is enough: how the decision was made to stop the FEAST trial: data and safety monitoring in an African trial of Fluid Expansion As Supportive Therapy (FEAST) for critically ill children.

PubMed

Todd, Jim; Heyderman, Robert S; Musoke, Philippa; Peto, Tim

2013-03-26

In resource-rich countries, bolus fluid expansion is routinely used for the treatment of poor perfusion and shock, but is less commonly used in many African settings. Controversial results from the recently completed FEAST (Fluid Expansion As Supportive Therapy) trial in African children have raised questions about the use of intravenous bolus fluid for the treatment of shock. Prior to the start of the trial, the Independent data monitoring committee (IDMC) developed stopping rules for the proof of benefit that bolus fluid resuscitation would bring. Although careful safety monitoring was put in place, there was less expectation that bolus fluid expansion would be harmful and differential stopping rules for harm were not formulated.In July 2010, two protocol amendments were agreed to increase the sample size from 2,880 to 3,600 children, and to increase bolus fluid administration. There was a non-significant trend against bolus treatment, but although the implications were discussed, the IDMC did not comment on the results, or on the amendments, in order to avoid inadvertent partial unblinding of the study.In January 2011, the trial was stopped for futility, as the combined intervention arms had significantly higher mortality (relative risk 1.46, 95% CI 1.13 to 1.90, P = 0.004) than the control arm. The stopping rule for proof of benefit was not achieved, and the IDMC stopped the trial with a lower level of significance (P = 0.01) due to futility and an increased risk of mortality from bolus fluid expansion in children enrolled in the trial. The basis for this decision was that the local standard of care was not to use bolus fluid for the care of children with shock in these African countries, and this was a different standard of care to that used in the UK. These decisions emphasize two important principles: firstly, the IDMC should avoid inadvertent unblinding of the trial by commenting on amendments, and secondly, when considering stopping a trial, the IDMC should be guided by the local standard of care rather than standards of care in other parts of the world.

Numerical judgments by chimpanzees (Pan troglodytes) in a token economy.

PubMed

Beran, Michael J; Evans, Theodore A; Hoyle, Daniel

2011-04-01

We presented four chimpanzees with a series of tasks that involved comparing two token sets or comparing a token set to a quantity of food. Selected tokens could be exchanged for food items on a one-to-one basis. Chimpanzees successfully selected the larger numerical set for comparisons of 1 to 5 items when both sets were visible and when sets were presented through one-by-one addition of tokens into two opaque containers. Two of four chimpanzees used the number of tokens and food items to guide responding in all conditions, rather than relying on token color, size, total amount, or duration of set presentation. These results demonstrate that judgments of simultaneous and sequential sets of stimuli are made by some chimpanzees on the basis of the numerousness of sets rather than other non-numerical dimensions. The tokens were treated as equivalent to food items on the basis of their numerousness, and the chimpanzees maximized reward by choosing the larger number of items in all situations.

Correlation consistent basis sets for actinides. I. The Th and U atoms

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

Peterson, Kirk A., E-mail: kipeters@wsu.edu

New correlation consistent basis sets based on both pseudopotential (PP) and all-electron Douglas-Kroll-Hess (DKH) Hamiltonians have been developed from double- to quadruple-zeta quality for the actinide atoms thorium and uranium. Sets for valence electron correlation (5f6s6p6d), cc − pV nZ − PP and cc − pV nZ − DK3, as well as outer-core correlation (valence + 5s5p5d), cc − pwCV nZ − PP and cc − pwCV nZ − DK3, are reported (n = D, T, Q). The -PP sets are constructed in conjunction with small-core, 60-electron PPs, while the -DK3 sets utilized the 3rd-order Douglas-Kroll-Hess scalar relativistic Hamiltonian. Bothmore » series of basis sets show systematic convergence towards the complete basis set limit, both at the Hartree-Fock and correlated levels of theory, making them amenable to standard basis set extrapolation techniques. To assess the utility of the new basis sets, extensive coupled cluster composite thermochemistry calculations of ThF{sub n} (n = 2 − 4), ThO{sub 2}, and UF{sub n} (n = 4 − 6) have been carried out. After accurately accounting for valence and outer-core correlation, spin-orbit coupling, and even Lamb shift effects, the final 298 K atomization enthalpies of ThF{sub 4}, ThF{sub 3}, ThF{sub 2}, and ThO{sub 2} are all within their experimental uncertainties. Bond dissociation energies of ThF{sub 4} and ThF{sub 3}, as well as UF{sub 6} and UF{sub 5}, were similarly accurate. The derived enthalpies of formation for these species also showed a very satisfactory agreement with experiment, demonstrating that the new basis sets allow for the use of accurate composite schemes just as in molecular systems composed only of lighter atoms. The differences between the PP and DK3 approaches were found to increase with the change in formal oxidation state on the actinide atom, approaching 5-6 kcal/mol for the atomization enthalpies of ThF{sub 4} and ThO{sub 2}. The DKH3 atomization energy of ThO{sub 2} was calculated to be smaller than the DKH2 value by ∼1 kcal/mol.« less

Segmented all-electron Gaussian basis sets of double and triple zeta qualities for Fr, Ra, and Ac

NASA Astrophysics Data System (ADS)

Campos, C. T.; de Oliveira, A. Z.; Ferreira, I. B.; Jorge, F. E.; Martins, L. S. C.

2017-05-01

Segmented all-electron basis sets of valence double and triple zeta qualities plus polarization functions for the elements Fr, Ra, and Ac are generated using non-relativistic and Douglas-Kroll-Hess (DKH) Hamiltonians. The sets are augmented with diffuse functions with the purpose to describe appropriately the electrons far from the nuclei. At the DKH-B3LYP level, first atomic ionization energies and bond lengths, dissociation energies, and polarizabilities of a sample of diatomics are calculated. Comparison with theoretical and experimental data available in the literature is carried out. It is verified that despite the small sizes of the basis sets, they are yet reliable.

Management of data from clinical trials using the ArchiMed system.

PubMed

Duftschmid, Georg; Gall, Walter; Eigenbauer, Ernst; Dorda, Wolfgang

2002-06-01

Clinical trials constitute a key source of medical research and are therefore conducted on a regular basis at university hospitals. The professional execution of trials requires, among other things, a repertoire of tools that support efficient data management. Tasks that are essential for efficient data management in clinical trials include the following: the design of the trial database, the design of electronic case report forms, recruiting patients, collection of data, and statistical analysis. The present article reports the manner in which these tasks are supported by the ArchiMed system at the University of Vienna and Graz Medical Schools. ArchiMed is customized for clinical end users, allowing them to autonomously manage their clinical trials without having to consult computer experts. An evaluation of the ArchiMed system in 12 trials recently conducted at the University of Vienna Medical School shows that the individual system functions can be usefully applied for data management in clinical trials.

Basis set and electron correlation effects on the polarizability and second hyperpolarizability of model open-shell π-conjugated systems

NASA Astrophysics Data System (ADS)

Champagne, Benoı̂t; Botek, Edith; Nakano, Masayoshi; Nitta, Tomoshige; Yamaguchi, Kizashi

2005-03-01

The basis set and electron correlation effects on the static polarizability (α) and second hyperpolarizability (γ) are investigated ab initio for two model open-shell π-conjugated systems, the C5H7 radical and the C6H8 radical cation in their doublet state. Basis set investigations evidence that the linear and nonlinear responses of the radical cation necessitate the use of a less extended basis set than its neutral analog. Indeed, double-zeta-type basis sets supplemented by a set of d polarization functions but no diffuse functions already provide accurate (hyper)polarizabilities for C6H8 whereas diffuse functions are compulsory for C5H7, in particular, p diffuse functions. In addition to the 6-31G*+pd basis set, basis sets resulting from removing not necessary diffuse functions from the augmented correlation consistent polarized valence double zeta basis set have been shown to provide (hyper)polarizability values of similar quality as more extended basis sets such as augmented correlation consistent polarized valence triple zeta and doubly augmented correlation consistent polarized valence double zeta. Using the selected atomic basis sets, the (hyper)polarizabilities of these two model compounds are calculated at different levels of approximation in order to assess the impact of including electron correlation. As a function of the method of calculation antiparallel and parallel variations have been demonstrated for α and γ of the two model compounds, respectively. For the polarizability, the unrestricted Hartree-Fock and unrestricted second-order Møller-Plesset methods bracket the reference value obtained at the unrestricted coupled cluster singles and doubles with a perturbative inclusion of the triples level whereas the projected unrestricted second-order Møller-Plesset results are in much closer agreement with the unrestricted coupled cluster singles and doubles with a perturbative inclusion of the triples values than the projected unrestricted Hartree-Fock results. Moreover, the differences between the restricted open-shell Hartree-Fock and restricted open-shell second-order Møller-Plesset methods are small. In what concerns the second hyperpolarizability, the unrestricted Hartree-Fock and unrestricted second-order Møller-Plesset values remain of similar quality while using spin-projected schemes fails for the charged system but performs nicely for the neutral one. The restricted open-shell schemes, and especially the restricted open-shell second-order Møller-Plesset method, provide for both compounds γ values close to the results obtained at the unrestricted coupled cluster level including singles and doubles with a perturbative inclusion of the triples. Thus, to obtain well-converged α and γ values at low-order electron correlation levels, the removal of spin contamination is a necessary but not a sufficient condition. Density-functional theory calculations of α and γ have also been carried out using several exchange-correlation functionals. Those employing hybrid exchange-correlation functionals have been shown to reproduce fairly well the reference coupled cluster polarizability and second hyperpolarizability values. In addition, inclusion of Hartree-Fock exchange is of major importance for determining accurate polarizability whereas for the second hyperpolarizability the gradient corrections are large.

Rational Density Functional Selection Using Game Theory.

PubMed

McAnanama-Brereton, Suzanne; Waller, Mark P

2018-01-22

Theoretical chemistry has a paradox of choice due to the availability of a myriad of density functionals and basis sets. Traditionally, a particular density functional is chosen on the basis of the level of user expertise (i.e., subjective experiences). Herein we circumvent the user-centric selection procedure by describing a novel approach for objectively selecting a particular functional for a given application. We achieve this by employing game theory to identify optimal functional/basis set combinations. A three-player (accuracy, complexity, and similarity) game is devised, through which Nash equilibrium solutions can be obtained. This approach has the advantage that results can be systematically improved by enlarging the underlying knowledge base, and the deterministic selection procedure mathematically justifies the density functional and basis set selections.

Assessment of multireference approaches to explicitly correlated full configuration interaction quantum Monte Carlo

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

Kersten, J. A. F., E-mail: jennifer.kersten@cantab.net; Alavi, Ali, E-mail: a.alavi@fkf.mpg.de; Max Planck Institute for Solid State Research, Heisenbergstraße 1, 70569 Stuttgart

2016-08-07

The Full Configuration Interaction Quantum Monte Carlo (FCIQMC) method has proved able to provide near-exact solutions to the electronic Schrödinger equation within a finite orbital basis set, without relying on an expansion about a reference state. However, a drawback to the approach is that being based on an expansion of Slater determinants, the FCIQMC method suffers from a basis set incompleteness error that decays very slowly with the size of the employed single particle basis. The FCIQMC results obtained in a small basis set can be improved significantly with explicitly correlated techniques. Here, we present a study that assesses andmore » compares two contrasting “universal” explicitly correlated approaches that fit into the FCIQMC framework: the [2]{sub R12} method of Kong and Valeev [J. Chem. Phys. 135, 214105 (2011)] and the explicitly correlated canonical transcorrelation approach of Yanai and Shiozaki [J. Chem. Phys. 136, 084107 (2012)]. The former is an a posteriori internally contracted perturbative approach, while the latter transforms the Hamiltonian prior to the FCIQMC simulation. These comparisons are made across the 55 molecules of the G1 standard set. We found that both methods consistently reduce the basis set incompleteness, for accurate atomization energies in small basis sets, reducing the error from 28 mE{sub h} to 3-4 mE{sub h}. While many of the conclusions hold in general for any combination of multireference approaches with these methodologies, we also consider FCIQMC-specific advantages of each approach.« less

Effects of Data Sampling on Graphical Depictions of Learning

ERIC Educational Resources Information Center

Carey, Mary-Katherine; Bourret, Jason C.

2014-01-01

Continuous and discontinuous data-collection methods were compared in the context of discrete-trial programming. Archival data sets were analyzed using trial sampling (1st 5 trials, 1st 3 trials, and 1st trial only) and session sampling (every other session, every 3rd session, and every 5th session). Results showed that trial sampling…

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

PubMed

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

2016-07-01

To compare the characteristics of individuals participating in randomized controlled trials (RCTs) of treatments of substance use disorder (SUD) with individuals receiving treatment in usual care settings, and to provide a summary quantitative measure of differences between characteristics of these two groups of individuals using propensity score methods. Design Analyses using data from RCT samples from the National Institute of Drug Abuse Clinical Trials Network (CTN) and target populations of patients drawn from the Treatment Episodes Data Set-Admissions (TEDS-A). Settings Multiple clinical trial sites and nation-wide usual SUD treatment settings in the United States. A total of 3592 individuals from 10 CTN samples and 1 602 226 individuals selected from TEDS-A between 2001 and 2009. Measurements The propensity scores for enrolling in the RCTs were computed based on the following nine observable characteristics: sex, race/ethnicity, age, education, employment status, marital status, admission to treatment through criminal justice, intravenous drug use and the number of prior treatments. Findings The proportion of those with ≥ 12 years of education and the proportion of those who had full-time jobs were significantly higher among RCT samples than among target populations (in seven and nine trials, respectively, at P < 0.001). The pooled difference in the mean propensity scores between the RCTs and the target population was 1.54 standard deviations and was statistically significant at P < 0.001. In the United States, individuals recruited into randomized controlled trials of substance use disorder treatments appear to be very different from individuals receiving treatment in usual care settings. Notably, RCT participants tend to have more years of education and a greater likelihood of full-time work compared with people receiving care in usual care settings. © 2016 Society for the Study of Addiction.

Detailed Wave Function Analysis for Multireference Methods: Implementation in the Molcas Program Package and Applications to Tetracene.

PubMed

Plasser, Felix; Mewes, Stefanie A; Dreuw, Andreas; González, Leticia

2017-11-14

High-level multireference computations on electronically excited and charged states of tetracene are performed, and the results are analyzed using an extensive wave function analysis toolbox that has been newly implemented in the Molcas program package. Aside from verifying the strong effect of dynamic correlation, this study reveals an unexpected critical influence of the atomic orbital basis set. It is shown that different polarized double-ζ basis sets produce significantly different results for energies, densities, and overall wave functions, with the best performance obtained for the atomic natural orbital (ANO) basis set by Pierloot et al. Strikingly, the ANO basis set not only reproduces the energies but also performs exceptionally well in terms of describing the diffuseness of the different states and of their attachment/detachment densities. This study, thus, not only underlines the fact that diffuse basis functions are needed for an accurate description of the electronic wave functions but also shows that, at least for the present example, it is enough to include them implicitly in the contraction scheme.

77 FR 6879 - Rules of Practice for Trials Before the Patent Trial and Appeal Board and Judicial Review of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-09

...The United States Patent and Trademark Office (Office or USPTO) proposes new rules of practice to implement the provisions of the Leahy-Smith America Invents Act that provide for trials before the Patent Trial and Appeal Board (Board). The proposed rules would provide a consolidated set of rules relating to Board trial practice for inter partes review, post-grant review, the transitional program for covered business method patents, and derivation proceedings. The proposed rules would also provide a consolidated set of rules to implement the provisions of the Leahy-Smith America Invents Act related to seeking judicial review of Board decisions.

Multiple Vaccinations: Friend or Foe

PubMed Central

Church, Sarah E.; Jensen, Shawn M.; Twitty, Chris; Bahjat, Keith; Hu, Hong-Ming; Urba, Walter J.; Fox, Bernard A.

2013-01-01

Few immunotherapists would accept the concept of a single vaccination inducing a therapeutic anti-cancer immune response in a patient with advanced cancer. But what is the evidence to support the “more-is-better” approach of multiple vaccinations? Since we are unaware of trials comparing the effect of a single vaccine versus multiple vaccinations on patient outcome, we considered that an anti-cancer immune response might provide a surrogate measure of the effectiveness of vaccination strategies. Since few large trials include immunological monitoring, the majority of information is gleaned from smaller trials in which an evaluation of immune responses to vaccine or tumor, before and at one or more times following the first vaccine was performed. In some studies there is convincing evidence that repeated administration of a specific vaccine can augment the immune response to antigens contained in the vaccine. In other settings multiple vaccinations can significantly reduce the immune response to one or more targets. Results from three large adjuvant vaccine studies support the potential detrimental effect of multiple vaccinations as clinical outcomes in the control arms were significantly better than that for treatment groups. Recent research has provided insights into mechanisms that are likely responsible for the reduced responses in the studies noted above, but supporting evidence from clinical specimens is generally lacking. Interpretation of these results is further complicated by the possibility that the dominant immune response may evolve to recognize epitopes not present in the vaccine. Nonetheless, the FDA-approval of the first therapeutic cancer vaccine and recent developments from preclinical models and clinical trials provide a substantial basis for optimism and a critical evaluation of cancer vaccine strategies. PMID:21952289

Anti-Aß immunotherapy in Alzheimer's disease; relevance of transgenic mouse studies to clinical trials

PubMed Central

Wilcock, Donna M.; Colton, Carol A.

2009-01-01

Therapeutic approaches to the treatment of Alzheimer's disease are focused primarily on the Aß peptide which aggregates to form amyloid deposits in the brain. The amyloid hypothesis states that amyloid is the precipitating factor that results in the other pathologies of Alzheimer's, namely neurofibrillary tangles and neurodegeneration, as well as the clinical dementia. One such therapy that has attracted significant attention is anti-Aß immunotherapy. First described in 1999, immunotherapy uses anti-Aß antibodies to lower brain amyloid levels. Active immunization, in which Aß is combined with an adjuvant to stimulate an immune response producing antibodies and passive immunization, in which antibodies are directly injected, were shown to lower brain amyloid levels and improve cognition in multiple transgenic mouse models. Mechanisms of action were studied in these mice and revealed a complex set of mechanisms that depended on the type of antibody used. When active immunization advanced to clinical trials a subset of patients developed meningoencephalitis; an event not predicted in mouse studies. However, it was suspected that a T-cell response due to the type of adjuvant used was the cause of the meningoencephalitis and studies in mice indicated alternative methods of vaccination. Passive immunization has also advanced to phase III clinical trials on the basis of successful transgenic mouse studies. Reports from the active immunization clinical trial indicated that, indeed, amyloid levels in brain were reduced. While APP transgenic mouse models are useful in studying amyloid pathology these mice do not generate significant tau pathology or neuron loss. Continued development of new mouse models that do generate all of these pathologies will be critical in more accurately testing therapeutics and predicting the clinical outcome of such therapeutics. PMID:19096156

Nudging and social marketing techniques encourage employees to make healthier food choices: a randomized controlled trial in 30 worksite cafeterias in The Netherlands.

PubMed

Velema, Elizabeth; Vyth, Ellis L; Hoekstra, Trynke; Steenhuis, Ingrid H M

2018-02-01

Currently, many studies focus on how the environment can be changed to encourage healthier eating behavior, referred to as choice architecture or "nudging." However, to date, these strategies are not often investigated in real-life settings, such as worksite cafeterias, or are only done so on a short-term basis. The objective of this study is to examine the effects of a healthy worksite cafeteria ["worksite cafeteria 2.0" (WC 2.0)] intervention on Dutch employees' purchase behavior over a 12-wk period. We conducted a randomized controlled trial in 30 worksite cafeterias. Worksite cafeterias were randomized to either the intervention or control group. The intervention aimed to encourage employees to make healthier food choices during their daily worksite cafeteria visits. The intervention consisted of 14 simultaneously executed strategies based on nudging and social marketing theories, involving product, price, placement, and promotion. Adjusted multilevel models showed significant positive effects of the intervention on purchases for 3 of the 7 studied product groups: healthier sandwiches, healthier cheese as a sandwich filling, and the inclusion of fruit. The increased sales of these healthier meal options were constant throughout the 12-wk intervention period. This study shows that the way worksite cafeterias offer products affects purchase behavior. Situated nudging and social marketing-based strategies are effective in promoting healthier choices and aim to remain effective over time. Some product groups only indicated an upward trend in purchases. Such an intervention could ultimately help prevent and reduce obesity in the Dutch working population. This trial was registered at the Dutch Trial Register (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5372) as NTR5372.

Video-based data acquisition system for use in eye blink classical conditioning procedures in sheep.

PubMed

Nation, Kelsey; Birge, Adam; Lunde, Emily; Cudd, Timothy; Goodlett, Charles; Washburn, Shannon

2017-10-01

Pavlovian eye blink conditioning (EBC) has been extensively studied in humans and laboratory animals, providing one of the best-understood models of learning in neuroscience. EBC has been especially useful in translational studies of cerebellar and hippocampal function. We recently reported a novel extension of EBC procedures for use in sheep, and now describe new advances in a digital video-based system. The system delivers paired presentations of conditioned stimuli (CSs; a tone) and unconditioned stimuli (USs; an air puff to the eye), or CS-alone "unpaired" trials. This system tracks the linear distance between the eyelids to identify blinks occurring as either unconditioned (URs) or conditioned (CRs) responses, to a resolution of 5 ms. A separate software application (Eye Blink Reviewer) is used to review and autoscore the trial CRs and URs, on the basis of a set of predetermined rules, permitting an operator to confirm (or rescore, if needed) the autoscore results, thereby providing quality control for accuracy of scoring. Learning curves may then be quantified in terms of the frequencies of CRs over sessions, both on trials with paired CS-US presentations and on CS-alone trials. The latency to CR onset, latency to CR peak, and occurrence of URs are also obtained. As we demonstrated in two example cases, this video-based system provides efficient automated means to conduct EBC in sheep and can facilitate fully powered studies with multigroup designs that involve paired and unpaired training. This can help extend new studies in sheep, a species well suited for translational studies of neurodevelopmental disorders resulting from gestational exposure to drugs, toxins, or intrauterine distress.

A cost minimization analysis of early correction of anterior crossbite—a randomized controlled trial

PubMed Central

Norlund, Anders; Petrén, Sofia; Bondemark, Lars

2016-01-01

Summary Objective: Economic evaluations provide an important basis for allocation of resources and health services planning. The aim of this study was to evaluate and compare the costs of correcting anterior crossbite with functional shift, using fixed or removable appliances (FA or RA) and to relate the costs to the effects, using cost-minimization analysis. Design, Setting, and Participants: Sixty-two patients with anterior crossbite and functional shift were randomized in blocks of 10. Thirty-one patients were randomized to be treated with brackets and arch wire (FA) and 31 with an acrylic plate (RA). Duration of treatment and number and estimated length of appointments and cancellations were registered. Direct costs (premises, staff salaries, material, and laboratory costs) and indirect costs (the accompanying parents’ loss of income while absent from work) were calculated and evaluated with reference to successful outcome alone, to successful and unsuccessful outcomes and to re-treatment when required. Societal costs were defined as the sum of direct and indirect costs. Interventions: Treatment with FA or RA. Results: There were no significant differences between FA and RA with respect to direct costs for treatment time, but both indirect costs and direct costs for material were significantly lower for FA. The total societal costs were lower for FA than for RA. Limitations: Costs depend on local factors and should not be directly extrapolated to other locations. Conclusion: The analysis disclosed significant economic benefits for FA over RA. Even when only successful outcomes were assessed, treatment with RA was more expensive. Trial registration: This trial was not registered. Protocol: The protocol was not published before trial commencement. PMID:25940585

Quality Control of Involved Field Radiotherapy in Patients With Early-Favorable (HD10) and Early-Unfavorable (HD11) Hodgkin's Lymphoma: An Analysis of the German Hodgkin Study Group

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

Eich, Hans Theodor; Engenhart-Cabillic, Rita; Hansemann, Katja

2008-08-01

Purpose: The German Hodgkin Study Group (GHSG) set up a radiotherapy (RT) reference center within the Department of Radiation Oncology at University of Cologne to undertake quality assurance of the group's clinical studies. In the HD10 trial (early-favorable stages) and HD11 trial (early-unfavorable stages) all patients received involved field (IF)-RT (30 Gy vs. 20 Gy) within a combined-modality approach. For these patients a central prospective review of all diagnostic imaging was performed by expert radiation oncologists to control disease extension and to define IF treatment volume. Methods and Materials: On the basis of simulation films, verification films, and radiotherapy casemore » report form (CRF) an expert panel evaluated retrospectively the adequacy of irradiated IF treatment portals according to the RT prescription, applied radiation doses, treatment time, and technical parameters. Results: Between 1999 and 2006 a total of 825 of 1370 randomized patients of the HD10 trial (60%) and 954 of 1422 patients of the HD11 trial (67%) were evaluated by the panel. Radiotherapy was rated as suboptimal in 47% of all reviewed cases. Although the participating RT centers received a precise RT prescription, most difficulties occurred in the adequate coverage of the IF (40%), followed by technical faults (12%). Deviations from the prescribed single daily dose (1.8-2 Gy), weekly dose, and total reference dose were rare (1%). Conclusions: As a consequence of these findings, radiation oncologists were trained on the definition of IF-RT at GHSG meetings and at the annual meetings of the German Society for Therapeutic Radiation Oncology. Possible correlations between RT quality and relapse rate will be investigated.« less

Effectiveness of an intensive E-mail based intervention in smoking cessation (TABATIC study): study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Intensive interventions on smoking cessation increase abstinence rates. However, few electronic mail (E-mail) based intensive interventions have been tested in smokers and none in primary care (PC) setting. The aim of the present study is to evaluate the effectiveness of an intensive E-mail based intervention in smokers attending PC services. Methods/design Randomized Controlled Multicentric Trial. Study population: 1060 smokers aged between 18–70 years from Catalonia, Salamanca and Aragón (Spain) who have and check regularly an E-mail account. Patients will be randomly assigned to control or intervention group. Intervention: Six phase intensive intervention with two face to face interviews and four automatically created and personal E-mail patients tracking, if needed other E-mail contacts will be made. Control group will receive a brief advice on smoking cessation. Outcome measures: Will be measured at 6 and 12 months after intervention: self reported continuous abstinence (confirmed by cooximetry), point prevalence abstinence, tobacco consumption, evolution of stage according to Prochaska and DiClemente's Stages of Change Model, length of visit, costs for the patient to access Primary Care Center. Statistical analysis: Descriptive and logistic and Poisson regression analysis under the intention to treat basis using SPSS v.17. Discussion The proposed intervention is an E-mail based intensive intervention in smokers attending primary care. Positive results could be useful to demonstrate a higher percentage of short and long-term abstinence among smokers attended in PC in Spain who regularly use E-mail. Furthermore, this intervention could be helpful in all health services to help smokers to quit. Trial Registration Clinical Trials.gov Identifier: NCT01494246. PMID:23597262

HIV Salvage Therapy Does Not Require Nucleoside Reverse Transcriptase Inhibitors: A Randomized, Controlled Trial.

PubMed

Tashima, Karen T; Smeaton, Laura M; Fichtenbaum, Carl J; Andrade, Adriana; Eron, Joseph J; Gandhi, Rajesh T; Johnson, Victoria A; Klingman, Karin L; Ritz, Justin; Hodder, Sally; Santana, Jorge L; Wilkin, Timothy; Haubrich, Richard H

2015-12-15

Nucleoside reverse transcriptase inhibitors (NRTIs) are often included in antiretroviral regimens in treatment-experienced patients in the absence of data from randomized trials. To compare treatment success between participants who omit versus those who add NRTIs to an optimized antiretroviral regimen of 3 or more agents. Multicenter, randomized, controlled trial. (ClinicalTrials.gov: NCT00537394). Outpatient HIV clinics. Treatment-experienced patients with HIV infection and viral resistance. Open-label optimized regimens (not including NRTIs) were selected on the basis of treatment history and susceptibility testing. Participants were randomly assigned to omit or add NRTIs. The primary efficacy outcome was regimen failure through 48 weeks using a noninferiority margin of 15%. The primary safety outcome was time to initial episode of a severe sign, symptom, or laboratory abnormality before discontinuation of NRTI assignment. 360 participants were randomly assigned, and 93% completed a 48-week visit. The cumulative probability of regimen failure was 29.8% in the omit-NRTIs group versus 25.9% in the add-NRTIs group (difference, 3.2 percentage points [95% CI, -6.1 to 12.5 percentage points]). No significant between-group differences were found in the primary safety end points or the proportion of participants with HIV RNA level less than 50 copies/mL. No deaths occurred in the omit-NRTIs group compared with 7 deaths in the add-NRTIs group. Unblinded study design, and the study may not be applicable to resource-poor settings. Treatment-experienced patients with HIV infection starting a new optimized regimen can safely omit NRTIs without compromising virologic efficacy. Omitting NRTIs will reduce pill burden, cost, and toxicity in this patient population. National Institute of Allergy and Infectious Diseases, Boehringer Ingelheim, Janssen, Merck, ViiV Healthcare, Roche, and Monogram Biosciences (LabCorp).

Trait aggressiveness modulates neurophysiological correlates of laboratory-induced reactive aggression in humans.

PubMed

Krämer, Ulrike M; Büttner, Sarah; Roth, Gerhard; Münte, Thomas F

2008-08-01

Reactive aggression following provocation is a frequent form of human social behavior. The neural basis of reactive aggression, especially its control, remains poorly understood, however. We conducted an event-related potential (ERP) study using a competitive reaction time task that elicits aggression through provocation. Participants were selected from a larger sample because of extreme scores in trait aggressiveness, yielding high and low trait aggressive groups. As each trial in the task is separated into a decision phase, during which the punishment level for the opponent is set, and an outcome phase, during which the punishment is applied or received, we were able to disentangle provocation-related and evaluation-related modulations of the ERPs during the aggressive interaction. Specifically, we observed an enhanced frontal negativity during the decision phase under high provocation that was positively correlated with the participants' ability to refrain from retaliation. This held true for high trait aggressive participants only, pointing to a higher need for inhibitory and control processes in these people when provoked. During the outcome phase, we detected a mediofrontal negativity in loss compared to win trials, resembling previous ERP findings to negative feedback stimuli, which have been linked to the evaluation of an outcome's valence. This mediofrontal negativity was differentially pronounced in aggressive and nonaggressive participants: Nonaggressive participants showed only a slightly smaller mediofrontal negativity in win than in loss trials, suggesting that for them punishing the opponent had a similar negative valence as being punished.

Naltrexone in alcohol dependence: a randomised controlled trial of effectiveness in a standard clinical setting.

PubMed

Latt, Noeline C; Jurd, Stephen; Houseman, Jennie; Wutzke, Sonia E

2002-06-03

To determine whether naltrexone is beneficial in the treatment of alcohol dependence in the absence of obligatory psychosocial intervention. Multicentre, randomised, double-blind, placebo-controlled trial. Hospital-based drug and alcohol clinics, 18 March 1998 - 22 October 1999. 107 patients (mean age, 45 years) fulfilling Diagnostic and statistical manual of mental disorders (4th edition) criteria for alcohol dependence. Patients with alcohol dependence were randomly allocated to naltrexone (50 mg/day) or placebo for 12 weeks. They were medically assessed, reviewed and advised by one physician, and encouraged to strive for abstinence and attend counselling and/or Alcoholics Anonymous, but this was not obligatory. Relapse rate; time to first relapse; side effects. On an intention-to-treat basis, the Kaplan-Meier survival curve showed a clear advantage in relapse rates for naltrexone over placebo (log-rank test, chi(2)(1) = 4.15; P = 0.042). This treatment effect was most marked in the first 6 weeks of the trial. The median time to relapse was 90 days for naltrexone, compared with 42 days for placebo. In absolute numbers, 19 of 56 patients (33.9%) taking naltrexone relapsed, compared with 27 of 51 patients (52.9%) taking placebo (P = 0.047). Naltrexone was well tolerated. Unlike previous studies, we have shown that naltrexone with adjunctive medical advice is effective in the treatment of alcohol dependence irrespective of whether it is accompanied by psychosocial interventions.

Long-Term Memory and the Control of Attentional Control

PubMed Central

Mayr, Ulrich; Kuhns, David; Hubbard, Jason

2014-01-01

Task-switch costs and in particular the switch-cost asymmetry (i.e., the larger costs of switching to a dominant than a non-dominant task) are usually explained in terms of trial-to-trial carry-over of task-specific control settings. Here we argue that task switches are just one example of situations that trigger a transition from working-memory maintenance to updating, thereby opening working memory to interference from long-term memory. We used a new paradigm that requires selecting a spatial location either on the basis of a central cue (i.e., endogenous control of attention) or a peripheral, sudden onset (i.e., exogenous control of attention). We found a strong cost asymmetry that occurred even after short interruptions of otherwise single-task blocks (Exp. 1-3), but that was much stronger when participants had experienced the competing task under conditions of conflict (Exp. 1-2). Experiment 3 showed that the asymmetric costs were due to interruptions per se, rather than to associative interference tied to specific interruption activities. Experiment 4 generalized the basic pattern across interruptions varying in length or control demands and Experiment 5 across primary tasks with response-selection conflict rather than attentional conflict. Combined, the results support a model in which costs of selecting control settings arise when (a) potentially interfering memory traces have been encoded in long-term memory and (b) working-memory is forced from a maintenance mode into an updating mode (e.g., through task interruptions), thereby allowing unwanted retrieval of the encoded memory traces. PMID:24650696

Describing different brain computer interface systems through a unique model: a UML implementation.

PubMed

Quitadamo, Lucia Rita; Marciani, Maria Grazia; Cardarilli, Gian Carlo; Bianchi, Luigi

2008-01-01

All the protocols currently implemented in brain computer interface (BCI) experiments are characterized by different structural and temporal entities. Moreover, due to the lack of a unique descriptive model for BCI systems, there is not a standard way to define the structure and the timing of a BCI experimental session among different research groups and there is also great discordance on the meaning of the most common terms dealing with BCI, such as trial, run and session. The aim of this paper is to provide a unified modeling language (UML) implementation of BCI systems through a unique dynamic model which is able to describe the main protocols defined in the literature (P300, mu-rhythms, SCP, SSVEP, fMRI) and demonstrates to be reasonable and adjustable according to different requirements. This model includes a set of definitions of the typical entities encountered in a BCI, diagrams which explain the structural correlations among them and a detailed description of the timing of a trial. This last represents an innovation with respect to the models already proposed in the literature. The UML documentation and the possibility of adapting this model to the different BCI systems built to date, make it a basis for the implementation of new systems and a mean for the unification and dissemination of resources. The model with all the diagrams and definitions reported in the paper are the core of the body language framework, a free set of routines and tools for the implementation, optimization and delivery of cross-platform BCI systems.

Community walking programs for treatment of peripheral artery disease

PubMed Central

Mays, Ryan J.; Rogers, R. Kevin; Hiatt, William R.; Regensteiner, Judith G.

2013-01-01

Background Supervised walking programs offered at medical facilities for patients with peripheral artery disease (PAD) and intermittent claudication (IC), while effective, are often not utilized due to barriers including lack of reimbursement and the need to travel to specialized locations for the training intervention. Walking programs for PAD patients that occur in community settings, such as those outside of supervised settings, may be a viable treatment option, as they are convenient and potentially bypass the need for supervised walking. This review evaluated the various methodologies and outcomes of community walking programs for PAD. Methods A literature review using appropriate search terms was conducted within PubMed/Medline and the Cochrane databases to identify studies in the English language employing community walking programs to treat PAD patients with IC. Search results were reviewed, and relevant articles were identified that form the basis of this review. The primary outcome was peak walking performance on the treadmill. Results Randomized controlled trials (n=10) examining peak walking outcomes in 558 PAD patients demonstrated that supervised exercise programs were more effective than community walking studies that consisted of general recommendations for patients with IC to walk at home. Recent community trials that incorporated more advice and feedback for PAD patients in general resulted in similar outcomes with no differences in peak walking time compared to supervised walking exercise groups. Conclusions Unstructured recommendations for patients with symptomatic PAD to exercise in the community are not efficacious. Community walking programs with more feedback and monitoring offer improvements in walking performance for patients with claudication and may bypass some obstacles associated with facility-based exercise programs. PMID:24103409

A trial of direct control of pine engraver beetles on a small logging unit

Treesearch

W. L. Jackson

1960-01-01

Laboratory tests and small-scale field trials have shown the insecticide lindane to be highly toxic to pine engraver beetles. On the basis of that information, the insecticide was applied to fresh logging slash heavily infested with pine engraver beetles at Challenge Experimental Forest in 1959. Costs were reasonable and no insurmountable problems were encountered....

Animal testing is still the best way to find new treatments for patients.

PubMed

Garattini, Silvio; Grignaschi, Giuliano

2017-04-01

Experimental research proceeds by hypotheses formulated on the basis of previous or new knowledge and then tested. If they are accepted, they serve as the basis for further hypotheses, and if they are rejected new hypotheses can be developed. In other words, when we are at the frontiers of knowledge the path is forged by "trial and error". When a trial shows a hypothesis is wrong, this is a step toward making fewer errors. This process also applies to drug development. There is no magic formula at present to predict - at the pre-clinical level - the therapeutic value of a drug for people with a disease. However, pre-clinical studies are needed in order to formulate hypotheses that justify clinical trials. Without these preliminary studies in vitro and in vivo in selected animal species it would be unethical to test still unproven chemicals in humans. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Convergence of third order correlation energy in atoms and molecules.

PubMed

Kahn, Kalju; Granovsky, Alex A; Noga, Jozef

2007-01-30

We have investigated the convergence of third order correlation energy within the hierarchies of correlation consistent basis sets for helium, neon, and water, and for three stationary points of hydrogen peroxide. This analysis confirms that singlet pair energies converge much slower than triplet pair energies. In addition, singlet pair energies with (aug)-cc-pVDZ and (aug)-cc-pVTZ basis sets do not follow a converging trend and energies with three basis sets larger than aug-cc-pVTZ are generally required for reliable extrapolations of third order correlation energies, making so the explicitly correlated R12 calculations preferable.

Sensitivity of the Properties of Ruthenium “Blue Dimer” to Method, Basis Set, and Continuum Model

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

Ozkanlar, Abdullah; Clark, Aurora E.

2012-05-23

The ruthenium “blue dimer” [(bpy)2RuIIIOH2]2O4+ is best known as the first well-defined molecular catalyst for water oxidation. It has been subject to numerous computational studies primarily employing density functional theory. However, those studies have been limited in the functionals, basis sets, and continuum models employed. The controversy in the calculated electronic structure and the reaction energetics of this catalyst highlights the necessity of benchmark calculations that explore the role of density functionals, basis sets, and continuum models upon the essential features of blue-dimer reactivity. In this paper, we report Kohn-Sham complete basis set (KS-CBS) limit extrapolations of the electronic structuremore » of “blue dimer” using GGA (BPW91 and BP86), hybrid-GGA (B3LYP), and meta-GGA (M06-L) density functionals. The dependence of solvation free energy corrections on the different cavity types (UFF, UA0, UAHF, UAKS, Bondi, and Pauling) within polarizable and conductor-like polarizable continuum model has also been investigated. The most common basis sets of double-zeta quality are shown to yield results close to the KS-CBS limit; however, large variations are observed in the reaction energetics as a function of density functional and continuum cavity model employed.« less

Application of the dual-kinetic-balance sets in the relativistic many-body problem of atomic structure

NASA Astrophysics Data System (ADS)

Beloy, Kyle; Derevianko, Andrei

2008-09-01

The dual-kinetic-balance (DKB) finite basis set method for solving the Dirac equation for hydrogen-like ions [V.M. Shabaev et al., Phys. Rev. Lett. 93 (2004) 130405] is extended to problems with a non-local spherically-symmetric Dirac-Hartree-Fock potential. We implement the DKB method using B-spline basis sets and compare its performance with the widely-employed approach of Notre Dame (ND) group [W.R. Johnson, S.A. Blundell, J. Sapirstein, Phys. Rev. A 37 (1988) 307-315]. We compare the performance of the ND and DKB methods by computing various properties of Cs atom: energies, hyperfine integrals, the parity-non-conserving amplitude of the 6s-7s transition, and the second-order many-body correction to the removal energy of the valence electrons. We find that for a comparable size of the basis set the accuracy of both methods is similar for matrix elements accumulated far from the nuclear region. However, for atomic properties determined by small distances, the DKB method outperforms the ND approach. In addition, we present a strategy for optimizing the size of the basis sets by choosing progressively smaller number of basis functions for increasingly higher partial waves. This strategy exploits suppression of contributions of high partial waves to typical many-body correlation corrections.

Spin-orbit ZORA and four-component Dirac-Coulomb estimation of relativistic corrections to isotropic nuclear shieldings and chemical shifts of noble gas dimers.

PubMed

Jankowska, Marzena; Kupka, Teobald; Stobiński, Leszek; Faber, Rasmus; Lacerda, Evanildo G; Sauer, Stephan P A

2016-02-05

Hartree-Fock and density functional theory with the hybrid B3LYP and general gradient KT2 exchange-correlation functionals were used for nonrelativistic and relativistic nuclear magnetic shielding calculations of helium, neon, argon, krypton, and xenon dimers and free atoms. Relativistic corrections were calculated with the scalar and spin-orbit zeroth-order regular approximation Hamiltonian in combination with the large Slater-type basis set QZ4P as well as with the four-component Dirac-Coulomb Hamiltonian using Dyall's acv4z basis sets. The relativistic corrections to the nuclear magnetic shieldings and chemical shifts are combined with nonrelativistic coupled cluster singles and doubles with noniterative triple excitations [CCSD(T)] calculations using the very large polarization-consistent basis sets aug-pcSseg-4 for He, Ne and Ar, aug-pcSseg-3 for Kr, and the AQZP basis set for Xe. For the dimers also, zero-point vibrational (ZPV) corrections are obtained at the CCSD(T) level with the same basis sets were added. Best estimates of the dimer chemical shifts are generated from these nuclear magnetic shieldings and the relative importance of electron correlation, ZPV, and relativistic corrections for the shieldings and chemical shifts is analyzed. © 2015 Wiley Periodicals, Inc.

Comparison of one-particle basis set extrapolation to explicitly correlated methods for the calculation of accurate quartic force fields, vibrational frequencies, and spectroscopic constants: Application to H2O, N2H+, NO2+, and C2H2

NASA Astrophysics Data System (ADS)

Huang, Xinchuan; Valeev, Edward F.; Lee, Timothy J.

2010-12-01

One-particle basis set extrapolation is compared with one of the new R12 methods for computing highly accurate quartic force fields (QFFs) and spectroscopic data, including molecular structures, rotational constants, and vibrational frequencies for the H2O, N2H+, NO2+, and C2H2 molecules. In general, agreement between the spectroscopic data computed from the best R12 and basis set extrapolation methods is very good with the exception of a few parameters for N2H+ where it is concluded that basis set extrapolation is still preferred. The differences for H2O and NO2+ are small and it is concluded that the QFFs from both approaches are more or less equivalent in accuracy. For C2H2, however, a known one-particle basis set deficiency for C-C multiple bonds significantly degrades the quality of results obtained from basis set extrapolation and in this case the R12 approach is clearly preferred over one-particle basis set extrapolation. The R12 approach used in the present study was modified in order to obtain high precision electronic energies, which are needed when computing a QFF. We also investigated including core-correlation explicitly in the R12 calculations, but conclude that current approaches are lacking. Hence core-correlation is computed as a correction using conventional methods. Considering the results for all four molecules, it is concluded that R12 methods will soon replace basis set extrapolation approaches for high accuracy electronic structure applications such as computing QFFs and spectroscopic data for comparison to high-resolution laboratory or astronomical observations, provided one uses a robust R12 method as we have done here. The specific R12 method used in the present study, CCSD(T)R12, incorporated a reformulation of one intermediate matrix in order to attain machine precision in the electronic energies. Final QFFs for N2H+ and NO2+ were computed, including basis set extrapolation, core-correlation, scalar relativity, and higher-order correlation and then used to compute highly accurate spectroscopic data for all isotopologues. Agreement with high-resolution experiment for 14N2H+ and 14N2D+ was excellent, but for 14N16O2+ agreement for the two stretching fundamentals is outside the expected residual uncertainty in the theoretical values, and it is concluded that there is an error in the experimental quantities. It is hoped that the highly accurate spectroscopic data presented for the minor isotopologues of N2H+ and NO2+ will be useful in the interpretation of future laboratory or astronomical observations.

Clinical Trials for Predictive Medicine—New Challenges and Paradigms*

PubMed Central

Simon, Richard

2014-01-01

Background Developments in biotechnology and genomics have increased the focus of biostatisticians on prediction problems. This has led to many exciting developments for predictive modeling where the number of variables is larger than the number of cases. Heterogeneity of human diseases and new technology for characterizing them presents new opportunities and challenges for the design and analysis of clinical trials. Purpose In oncology, treatment of broad populations with regimens that do not benefit most patients is less economically sustainable with expensive molecularly targeted therapeutics. The established molecular heterogeneity of human diseases requires the development of new paradigms for the design and analysis of randomized clinical trials as a reliable basis for predictive medicine[1, 2]. Results We have reviewed prospective designs for the development of new therapeutics with candidate predictive biomarkers. We have also outlined a prediction based approach to the analysis of randomized clinical trials that both preserves the type I error and provides a reliable internally validated basis for predicting which patients are most likely or unlikely to benefit from the new regimen. Conclusions Developing new treatments with predictive biomarkers for identifying the patients who are most likely or least likely to benefit makes drug development more complex. But for many new oncology drugs it is the only science based approach and should increase the chance of success. It may also lead to more consistency in results among trials and has obvious benefits for reducing the number of patients who ultimately receive expensive drugs which expose them risks of adverse events but no benefit. This approach also has great potential value for controlling societal expenditures on health care. Development of treatments with predictive biomarkers requires major changes in the standard paradigms for the design and analysis of clinical trials. Some of the key assumptions upon which current methods are based are no longer valid. In addition to reviewing a variety of new clinical trial designs for co-development of treatments and predictive biomarkers, we have outlined a prediction based approach to the analysis of randomized clinical trials. This is a very structured approach whose use requires careful prospective planning. It requires further development but may serve as a basis for a new generation of predictive clinical trials which provide the kinds of reliable individualized information which physicians and patients have long sought, but which have not been available from the past use of post-hoc subset analysis. PMID:20338899

Toward a W4-F12 approach: Can explicitly correlated and orbital-based ab initio CCSD(T) limits be reconciled?

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

Sylvetsky, Nitai, E-mail: gershom@weizmann.ac.il; Martin, Jan M. L., E-mail: gershom@weizmann.ac.il; Peterson, Kirk A., E-mail: kipeters@wsu.edu

2016-06-07

In the context of high-accuracy computational thermochemistry, the valence coupled cluster with all singles and doubles (CCSD) correlation component of molecular atomization energies presents the most severe basis set convergence problem, followed by the (T) component. In the present paper, we make a detailed comparison, for an expanded version of the W4-11 thermochemistry benchmark, between, on the one hand, orbital-based CCSD/AV{5,6}Z + d and CCSD/ACV{5,6}Z extrapolation, and on the other hand CCSD-F12b calculations with cc-pVQZ-F12 and cc-pV5Z-F12 basis sets. This latter basis set, now available for H–He, B–Ne, and Al–Ar, is shown to be very close to the basis setmore » limit. Apparent differences (which can reach 0.35 kcal/mol for systems like CCl{sub 4}) between orbital-based and CCSD-F12b basis set limits disappear if basis sets with additional radial flexibility, such as ACV{5,6}Z, are used for the orbital calculation. Counterpoise calculations reveal that, while total atomization energies with V5Z-F12 basis sets are nearly free of BSSE, orbital calculations have significant BSSE even with AV(6 + d)Z basis sets, leading to non-negligible differences between raw and counterpoise-corrected extrapolated limits. This latter problem is greatly reduced by switching to ACV{5,6}Z core-valence basis sets, or simply adding an additional zeta to just the valence orbitals. Previous reports that all-electron approaches like HEAT (high-accuracy extrapolated ab-initio thermochemistry) lead to different CCSD(T) limits than “valence limit + CV correction” approaches like Feller-Peterson-Dixon and Weizmann-4 (W4) theory can be rationalized in terms of the greater radial flexibility of core-valence basis sets. For (T) corrections, conventional CCSD(T)/AV{Q,5}Z + d calculations are found to be superior to scaled or extrapolated CCSD(T)-F12b calculations of similar cost. For a W4-F12 protocol, we recommend obtaining the Hartree-Fock and valence CCSD components from CCSD-F12b/cc-pV{Q,5}Z-F12 calculations, but the (T) component from conventional CCSD(T)/aug’-cc-pV{Q,5}Z + d calculations using Schwenke’s extrapolation; post-CCSD(T), core-valence, and relativistic corrections are to be obtained as in the original W4 theory. W4-F12 is found to agree slightly better than W4 with ATcT (active thermochemical tables) data, at a substantial saving in computation time and especially I/O overhead. A W4-F12 calculation on benzene is presented as a proof of concept.« less

Creation of a core outcome set for clinical trials of people with shoulder pain: a study protocol.

PubMed

Gagnier, Joel J; Page, Matthew J; Huang, Hsiaomin; Verhagen, Arianne P; Buchbinder, Rachelle

2017-07-20

The selection of appropriate outcomes or domains is crucial when designing clinical trials, to appreciate the effects of different interventions, pool results, and make valid comparisons between trials. If the findings are to influence policy and practice, then the chosen outcomes need to be relevant and important to key stakeholders, including patients and the public, healthcare professionals and others making decisions about health care. There is a growing recognition that insufficient attention has been paid to the outcomes measured in clinical trials. Recent reviews of the measurement properties of patient-reported outcome measures for shoulder disorders revealed a large selection of diverse measures, many with questionable validity, reliability, and responsiveness. These issues could be addressed through the development and use of an agreed standardized collection of outcomes, known as a core outcome set (COS), which should be measured and reported in all trials of shoulder disorders. The purpose of the present project is to develop and disseminate a COS for clinical trials in shoulder disorders. The methods for the COS development will include 3 phases: (1) a comprehensive review of the core domains used in shoulder disorder trials; (2) an international Delphi study involving relevant stakeholders (patients, clinicians, scientists) to define which domains should be core; and (3) an international focus group informed by the evidence identified in phases 1 and 2, to determine which measurement instruments best measure the core domains and identification of any evidence gaps that require further empiric evidence. The aim of the current proposal is to convene several meetings of international experts and patients to develop a COS for clinical trials of shoulder disorders and to develop an implementation strategy to ensure rapid uptake of the core set of outcomes in clinical trials. There would be an expectation that the core set of outcomes would always be collected and reported, but it would not preclude use of additional outcomes in a particular trial.

Outdoor Biology Instructional Strategies Trial Edition. Set II.

ERIC Educational Resources Information Center

Fairwell, Kay, Ed.; And Others

The 24 activities in the Outdoor Biology Instructional Strategies (OBIS) Trial Edition Set II use living organisms such as crabs, birds, crayfish, lichens, and insects to investigate biological interrelationships, organism behavior, and species density to promote greater environmental and sensory awareness. The activities, designed primarily for…

A converged calculation of the energy barrier to internal rotation in the ethylene-sulfur dioxide dimer

NASA Astrophysics Data System (ADS)

Resende, Stella M.; De Almeida, Wagner B.; van Duijneveldt-van de Rijdt, Jeanne G. C. M.; van Duijneveldt, Frans B.

2001-08-01

Geometrical parameters for the equilibrium (MIN) and lowest saddle-point (TS) geometries of the C2H4⋯SO2 dimer, and the corresponding binding energies, were calculated using the Hartree-Fock and correlated levels of ab initio theory, in basis sets ranging from the D95(d,p) double-zeta basis set to the aug-cc-pVQZ correlation consistent basis set. An assessment of the effect of the basis set superposition error (BSSE) on these results was made. The dissociation energy from the lowest vibrational state was estimated to be 705±100 cm-1 at the basis set limit, which is well within the range expected from experiment. The barrier to internal rotation was found to be 53±5 cm-1, slightly higher than the (revised) experimental result of 43 cm-1, probably due to zero-point vibrational effects. Our results clearly show that, in direct contrast with recent ideas, the BSSE correction affects differentially the MIN and TS binding energies and so has to be included in the calculation of small energy barriers such as that in the C2H4⋯SO2 dimer. Previous reports of positive MP2 frozen-core binding energies for this complex in basis D95(d,p) are confirmed. The anomalies are shown to be an artifact arising from an incorrect removal of virtual orbitals by the default frozen-core option in the GAUSSIAN program.

Meshless Local Petrov-Galerkin Euler-Bernoulli Beam Problems: A Radial Basis Function Approach

NASA Technical Reports Server (NTRS)

Raju, I. S.; Phillips, D. R.; Krishnamurthy, T.

2003-01-01

A radial basis function implementation of the meshless local Petrov-Galerkin (MLPG) method is presented to study Euler-Bernoulli beam problems. Radial basis functions, rather than generalized moving least squares (GMLS) interpolations, are used to develop the trial functions. This choice yields a computationally simpler method as fewer matrix inversions and multiplications are required than when GMLS interpolations are used. Test functions are chosen as simple weight functions as in the conventional MLPG method. Compactly and noncompactly supported radial basis functions are considered. The non-compactly supported cubic radial basis function is found to perform very well. Results obtained from the radial basis MLPG method are comparable to those obtained using the conventional MLPG method for mixed boundary value problems and problems with discontinuous loading conditions.

Assuring high quality treatment delivery in clinical trials - Results from the Trans-Tasman Radiation Oncology Group (TROG) study 03.04 "RADAR" set-up accuracy study.

PubMed

Haworth, Annette; Kearvell, Rachel; Greer, Peter B; Hooton, Ben; Denham, James W; Lamb, David; Duchesne, Gillian; Murray, Judy; Joseph, David

2009-03-01

A multi-centre clinical trial for prostate cancer patients provided an opportunity to introduce conformal radiotherapy with dose escalation. To verify adequate treatment accuracy prior to patient recruitment, centres submitted details of a set-up accuracy study (SUAS). We report the results of the SUAS, the variation in clinical practice and the strategies used to help centres improve treatment accuracy. The SUAS required each of the 24 participating centres to collect data on at least 10 pelvic patients imaged on a minimum of 20 occasions. Software was provided for data collection and analysis. Support to centres was provided through educational lectures, the trial quality assurance team and an information booklet. Only two centres had recently carried out a SUAS prior to the trial opening. Systematic errors were generally smaller than those previously reported in the literature. The questionnaire identified many differences in patient set-up protocols. As a result of participating in this QA activity more than 65% of centres improved their treatment delivery accuracy. Conducting a pre-trial SUAS has led to improvement in treatment delivery accuracy in many centres. Treatment techniques and set-up accuracy varied greatly, demonstrating a need to ensure an on-going awareness for such studies in future trials and with the introduction of dose escalation or new technologies.

Genetic basis of nitrogen use efficiency and yield stability across environments in winter rapeseed.

PubMed

Bouchet, Anne-Sophie; Laperche, Anne; Bissuel-Belaygue, Christine; Baron, Cécile; Morice, Jérôme; Rousseau-Gueutin, Mathieu; Dheu, Jean-Eric; George, Pierre; Pinochet, Xavier; Foubert, Thomas; Maes, Olivier; Dugué, Damien; Guinot, Florent; Nesi, Nathalie

2016-09-15

Nitrogen use efficiency is an important breeding trait that can be modified to improve the sustainability of many crop species used in agriculture. Rapeseed is a major oil crop with low nitrogen use efficiency, making its production highly dependent on nitrogen input. This complex trait is suspected to be sensitive to genotype × environment interactions, especially genotype × nitrogen interactions. Therefore, phenotyping diverse rapeseed populations under a dense network of trials is a powerful approach to study nitrogen use efficiency in this crop. The present study aimed to determine the quantitative trait loci (QTL) associated with yield in winter oilseed rape and to assess the stability of these regions under contrasting nitrogen conditions for the purpose of increasing nitrogen use efficiency. Genome-wide association studies and linkage analyses were performed on two diversity sets and two doubled-haploid populations. These populations were densely genotyped, and yield-related traits were scored in a multi-environment design including seven French locations, six growing seasons (2009 to 2014) and two nitrogen nutrition levels (optimal versus limited). Very few genotype × nitrogen interactions were detected, and a large proportion of the QTL were stable across nitrogen nutrition conditions. In contrast, strong genotype × trial interactions in which most of the QTL were specific to a single trial were found. To obtain further insight into the QTL × environment interactions, genetic analyses of ecovalence were performed to identify the genomic regions contributing to the genotype × nitrogen and genotype × trial interactions. Fifty-one critical genomic regions contributing to the additive genetic control of yield-associated traits were identified, and the structural organization of these regions in the genome was investigated. Our results demonstrated that the effect of the trial was greater than the effect of nitrogen nutrition levels on seed yield-related traits under our experimental conditions. Nevertheless, critical genomic regions associated with yield that were stable across environments were identified in rapeseed.

A Randomized Pilot Trial of Remote Ischemic Preconditioning in Heart Failure with Reduced Ejection Fraction

PubMed Central

McDonald, Michael A.; Braga, Juarez R.; Li, Jing; Manlhiot, Cedric; Ross, Heather J.; Redington, Andrew N.

2014-01-01

Background Remote ischemic preconditioning (RIPC) induced by transient limb ischemia confers multi-organ protection and improves exercise performance in the setting of tissue hypoxia. We aimed to evaluate the effect of RIPC on exercise capacity in heart failure patients. Methods We performed a randomized crossover trial of RIPC (4×5-minutes limb ischemia) compared to sham control in heart failure patients undergoing exercise testing. Patients were randomly allocated to either RIPC or sham prior to exercise, then crossed over and completed the alternate intervention with repeat testing. The primary outcome was peak VO2, RIPC versus sham. A mechanistic substudy was performed using dialysate from study patient blood samples obtained after sham and RIPC. This dialysate was used to test for a protective effect of RIPC in a mouse heart Langendorff model of infarction. Mouse heart infarct size with RIPC or sham dialysate exposure was also compared with historical control data. Results Twenty patients completed the study. RIPC was not associated with improvements in peak VO2 (15.6+/−4.2 vs 15.3+/−4.6 mL/kg/min; p = 0.53, sham and RIPC, respectively). In our Langendorff sub-study, infarct size was similar between RIPC and sham dialysate groups from our study patients, but was smaller than expected compared to healthy controls (29.0%, 27.9% [sham, RIPC] vs 51.2% [controls]. We observed less preconditioning among the subgroup of patients with increased exercise performance following RIPC (p<0.04). Conclusion In this pilot study of RIPC in heart failure patients, RIPC was not associated with improvements in exercise capacity overall. However, the degree of effect of RIPC may be inversely related to the degree of baseline preconditioning. These data provide the basis for a larger randomized trial to test the potential benefits of RIPC in patients with heart failure. Trial Registration ClinicalTrials.gov +++++NCT01128790 PMID:25181050

A randomised controlled trial of low-dose aspirin for the prevention of fractures in healthy older people: protocol for the ASPREE-Fracture substudy.

PubMed

Barker, Anna L; McNeil, John J; Seeman, Ego; Ward, Stephanie A; Sanders, Kerrie M; Khosla, Sundeep; Cumming, Robert G; Pasco, Julie A; Bohensky, Megan A; Ebeling, Peter R; Woods, Robyn L; Lockery, Jessica E; Wolfe, Rory; Talevski, Jason

2016-08-01

Disability, mortality and healthcare burden from fractures in older people is a growing problem worldwide. Observational studies suggest that aspirin may reduce fracture risk. While these studies provide room for optimism, randomised controlled trials are needed. This paper describes the rationale and design of the ASPirin in Reducing Events in the Elderly (ASPREE)-Fracture substudy, which aims to determine whether daily low-dose aspirin decreases fracture risk in healthy older people. ASPREE is a double-blind, randomised, placebo-controlled primary prevention trial designed to assess whether daily active treatment using low-dose aspirin extends the duration of disability-free and dementia-free life in 19 000 healthy older people recruited from Australian and US community settings. This substudy extends the ASPREE trial data collection to determine the effect of daily low-dose aspirin on fracture and fall-related hospital presentation risk in the 16 500 ASPREE participants aged ≥70 years recruited in Australia. The intervention is a once daily dose of enteric-coated aspirin (100 mg) versus a matching placebo, randomised on a 1:1 basis. The primary outcome for this substudy is the occurrence of any fracture-vertebral, hip and non-vert-non-hip-occurring post randomisation. Fall-related hospital presentations are a secondary outcome. This substudy will determine whether a widely available, simple and inexpensive health intervention-aspirin-reduces the risk of fractures in older Australians. If it is demonstrated to safely reduce the risk of fractures and serious falls, it is possible that aspirin might provide a means of fracture prevention. The protocol for this substudy is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000347561). 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/

Towards a Science of Community Stakeholder Engagement in Biomedical HIV Prevention Trials: An Embedded Four-Country Case Study.

PubMed

Newman, Peter A; Rubincam, Clara; Slack, Catherine; Essack, Zaynab; Chakrapani, Venkatesan; Chuang, Deng-Min; Tepjan, Suchon; Shunmugam, Murali; Roungprakhon, Surachet; Logie, Carmen; Koen, Jennifer; Lindegger, Graham

2015-01-01

Broad international guidelines and studies in the context of individual clinical trials highlight the centrality of community stakeholder engagement in conducting ethically rigorous HIV prevention trials. We explored and identified challenges and facilitators for community stakeholder engagement in biomedical HIV prevention trials in diverse global settings. Our aim was to assess and deepen the empirical foundation for priorities included in the GPP guidelines and to highlight challenges in implementation that may merit further attention in subsequent GPP iterations. From 2008-2012 we conducted an embedded, multiple case study centered in Thailand, India, South Africa and Canada. We conducted in-depth interviews and focus groups with respondents from different trial-related subsystems: civil society organization representatives, community advocates, service providers, clinical trialists/researchers, former trial participants, and key HIV risk populations. Interviews/focus groups were recorded, and coded using thematic content analysis. After intra-case analyses, we conducted cross-case analysis to contrast and synthesize themes and sub-themes across cases. Lastly, we applied the case study findings to explore and assess UNAIDS/AVAC GPP guidelines and the GPP Blueprint for Stakeholder Engagement. Across settings, we identified three cross-cutting themes as essential to community stakeholder engagement: trial literacy, including lexicon challenges and misconceptions that imperil sound communication; mistrust due to historical exploitation; and participatory processes: engaging early; considering the breadth of "community"; and, developing appropriate stakeholder roles. Site-specific challenges arose in resource-limited settings and settings where trials were halted. This multiple case study revealed common themes underlying community stakeholder engagement across four country settings that largely mirror GPP goals and the GPP Blueprint, as well as highlighting challenges in the implementation of important guidelines. GPP guidance documents could be strengthened through greater focus on: identifying and addressing the community-specific roots of mistrust and its impact on trial literacy activities; achieving and evaluating representativeness in community stakeholder groups; and addressing the impact of power and funding streams on meaningful engagement and independent decision-making.

Towards a Science of Community Stakeholder Engagement in Biomedical HIV Prevention Trials: An Embedded Four-Country Case Study

PubMed Central

Newman, Peter A.; Rubincam, Clara; Slack, Catherine; Essack, Zaynab; Chakrapani, Venkatesan; Chuang, Deng-Min; Tepjan, Suchon; Shunmugam, Murali; Roungprakhon, Surachet; Logie, Carmen; Koen, Jennifer; Lindegger, Graham

2015-01-01

Objectives Broad international guidelines and studies in the context of individual clinical trials highlight the centrality of community stakeholder engagement in conducting ethically rigorous HIV prevention trials. We explored and identified challenges and facilitators for community stakeholder engagement in biomedical HIV prevention trials in diverse global settings. Our aim was to assess and deepen the empirical foundation for priorities included in the GPP guidelines and to highlight challenges in implementation that may merit further attention in subsequent GPP iterations. Methods From 2008–2012 we conducted an embedded, multiple case study centered in Thailand, India, South Africa and Canada. We conducted in-depth interviews and focus groups with respondents from different trial-related subsystems: civil society organization representatives, community advocates, service providers, clinical trialists/researchers, former trial participants, and key HIV risk populations. Interviews/focus groups were recorded, and coded using thematic content analysis. After intra-case analyses, we conducted cross-case analysis to contrast and synthesize themes and sub-themes across cases. Lastly, we applied the case study findings to explore and assess UNAIDS/AVAC GPP guidelines and the GPP Blueprint for Stakeholder Engagement. Results Across settings, we identified three cross-cutting themes as essential to community stakeholder engagement: trial literacy, including lexicon challenges and misconceptions that imperil sound communication; mistrust due to historical exploitation; and participatory processes: engaging early; considering the breadth of “community”; and, developing appropriate stakeholder roles. Site-specific challenges arose in resource-limited settings and settings where trials were halted. Conclusions This multiple case study revealed common themes underlying community stakeholder engagement across four country settings that largely mirror GPP goals and the GPP Blueprint, as well as highlighting challenges in the implementation of important guidelines. GPP guidance documents could be strengthened through greater focus on: identifying and addressing the community-specific roots of mistrust and its impact on trial literacy activities; achieving and evaluating representativeness in community stakeholder groups; and addressing the impact of power and funding streams on meaningful engagement and independent decision-making. PMID:26295159

Variance in population firing rate as a measure of slow time-scale correlation

PubMed Central

Snyder, Adam C.; Morais, Michael J.; Smith, Matthew A.

2013-01-01

Correlated variability in the spiking responses of pairs of neurons, also known as spike count correlation, is a key indicator of functional connectivity and a critical factor in population coding. Underscoring the importance of correlation as a measure for cognitive neuroscience research is the observation that spike count correlations are not fixed, but are rather modulated by perceptual and cognitive context. Yet while this context fluctuates from moment to moment, correlation must be calculated over multiple trials. This property undermines its utility as a dependent measure for investigations of cognitive processes which fluctuate on a trial-to-trial basis, such as selective attention. A measure of functional connectivity that can be assayed on a moment-to-moment basis is needed to investigate the single-trial dynamics of populations of spiking neurons. Here, we introduce the measure of population variance in normalized firing rate for this goal. We show using mathematical analysis, computer simulations and in vivo data how population variance in normalized firing rate is inversely related to the latent correlation in the population, and how this measure can be used to reliably classify trials from different typical correlation conditions, even when firing rate is held constant. We discuss the potential advantages for using population variance in normalized firing rate as a dependent measure for both basic and applied neuroscience research. PMID:24367326

Outdoor Biology Instructional Strategies Trial Edition. Set III.

ERIC Educational Resources Information Center

Fairwell, Kay, Ed.; And Others

The predominant focus of the 24 Outdoor Biology Instructional Strategies (OBIS) Trial Edition Set III activities is on animal behavior, and the adaptations and diversity of both plants and animals. Night time activities, games, investigation, experimentation, and crafts are used to study ants, birds, clams, water snails, water striders, spiders,…

Outdoor Biology Instructional Strategies Trial Edition. Set I.

ERIC Educational Resources Information Center

Fairwell, Kay, Ed.; And Others

The Outdoor Biology Instructional Strategies (OBIS) Trial Edition Set I contains 24 varied activities which make use of crafts, simulations, and basic investigative techniques to provide introductory learning experiences in outdoor biology for children aged 10 to 15. The individual water-resistant folio for each activity includes biological…

Object-oriented business process analysis of the cooperative soft tissue sarcoma trial of the german society for paediatric oncology and haematology (GPOH).

PubMed

Weber, R; Knaup, P; Knietitg, R; Haux, R; Merzweiler, A; Mludek, V; Schilling, F H; Wiedemann, T

2001-01-01

The German Society for Paediatric Oncology and Haematology (GPOH) runs nation-wide multicentre clinical trials to improve the treatment of children suffering from malignant diseases. We want to provide methods and tools to support the centres of these trials in developing trial specific modules for the computer-based DOcumentation System for Paediatric Oncology (DOSPO). For this we carried out an object-oriented business process analysis for the Cooperative Soft Tissue Sarcoma Trial at the Olgahospital Stuttgart for Child and Adolescent Medicine. The result is a comprehensive business process model consisting of UML-diagrams and use case specifications. We recommend the object-oriented business process analysis as a method for the definition of requirements in information processing projects in the field of clinical trials in general. For this our model can serve as basis because it slightly can be adjusted to each type of clinical trial.

Online adaptation and over-trial learning in macaque visuomotor control.

PubMed

Braun, Daniel A; Aertsen, Ad; Paz, Rony; Vaadia, Eilon; Rotter, Stefan; Mehring, Carsten

2011-01-01

When faced with unpredictable environments, the human motor system has been shown to develop optimized adaptation strategies that allow for online adaptation during the control process. Such online adaptation is to be contrasted to slower over-trial learning that corresponds to a trial-by-trial update of the movement plan. Here we investigate the interplay of both processes, i.e., online adaptation and over-trial learning, in a visuomotor experiment performed by macaques. We show that simple non-adaptive control schemes fail to perform in this task, but that a previously suggested adaptive optimal feedback control model can explain the observed behavior. We also show that over-trial learning as seen in learning and aftereffect curves can be explained by learning in a radial basis function network. Our results suggest that both the process of over-trial learning and the process of online adaptation are crucial to understand visuomotor learning.

Online Adaptation and Over-Trial Learning in Macaque Visuomotor Control

PubMed Central

Braun, Daniel A.; Aertsen, Ad; Paz, Rony; Vaadia, Eilon; Rotter, Stefan; Mehring, Carsten

2011-01-01

When faced with unpredictable environments, the human motor system has been shown to develop optimized adaptation strategies that allow for online adaptation during the control process. Such online adaptation is to be contrasted to slower over-trial learning that corresponds to a trial-by-trial update of the movement plan. Here we investigate the interplay of both processes, i.e., online adaptation and over-trial learning, in a visuomotor experiment performed by macaques. We show that simple non-adaptive control schemes fail to perform in this task, but that a previously suggested adaptive optimal feedback control model can explain the observed behavior. We also show that over-trial learning as seen in learning and aftereffect curves can be explained by learning in a radial basis function network. Our results suggest that both the process of over-trial learning and the process of online adaptation are crucial to understand visuomotor learning. PMID:21720526

Cardiac magnetic resonance imaging parameters as surrogate endpoints in clinical trials of acute myocardial infarction

PubMed Central

2011-01-01

Cardiac magnetic resonance (CMR) offers a variety of parameters potentially suited as surrogate endpoints in clinical trials of acute myocardial infarction such as infarct size, myocardial salvage, microvascular obstruction or left ventricular volumes and ejection fraction. The present article reviews each of these parameters with regard to the pathophysiological basis, practical aspects, validity, reliability and its relative value (strengths and limitations) as compared to competitive modalities. Randomized controlled trials of acute myocardial infarction which have used CMR parameters as a primary endpoint are presented. PMID:21917147

Interference, aging, and visuospatial working memory: the role of similarity.

PubMed

Rowe, Gillian; Hasher, Lynn; Turcotte, Josée

2010-11-01

Older adults' performance on working memory (WM) span tasks is known to be negatively affected by the buildup of proactive interference (PI) across trials. PI has been reduced in verbal tasks and performance increased by presenting distinctive items across trials. In addition, reversing the order of trial presentation (i.e., starting with the longest sets first) has been shown to reduce PI in both verbal and visuospatial WM span tasks. We considered whether making each trial visually distinct would improve older adults' visuospatial WM performance, and whether combining the 2 PI-reducing manipulations, distinct trials and reversed order of presentation, would prove additive, thus providing even greater benefit. Forty-eight healthy older adults (age range = 60-77 years) completed 1 of 3 versions of a computerized Corsi block test. For 2 versions of the task, trials were either all visually similar or all visually distinct, and were presented in the standard ascending format (shortest set size first). In the third version, visually distinct trials were presented in a reverse order of presentation (longest set size first). Span scores were reliably higher in the ascending version for visually distinct compared with visually similar trials, F(1, 30) = 4.96, p = .03, η² = .14. However, combining distinct trials and a descending format proved no more beneficial than administering the descending format alone. Our findings suggest that a more accurate measurement of the visuospatial WM span scores of older adults (and possibly neuropsychological patients) might be obtained by reducing within-test interference.

Reaching clinically relevant outcome measures for new pharmacotherapy and immunotherapy of atopic eczema.

PubMed

Chalmers, Joanne; Deckert, Stefanie; Schmitt, Jochen

2015-06-01

This article describes the core outcome set (COS) for atopic eczema trials. COS describe a minimum set of outcomes to be assessed in a defined situation. COS are required to overcome the current situation of different trials using different endpoints with unclear/insufficient measurement properties resulting in incomparable trials. The global multi-stakeholder Harmonising Outcomes Measures for Eczema initiative developed the Harmonising Outcomes Measures for Eczema roadmap as a generic framework for COS development. Following the establishment of a panel representing all stakeholders, a core set of outcome domains need to be selected based on systematic reviews and consensus methods. Outcome measurement instruments to assess these core domains need to be valid, reliable, and feasible. There is broad global consensus that clinical signs, quality of life, symptoms, and long-term control of flares form the COS for atopic eczema trials. The Eczema Area and Severity Index is recommended to assess clinical signs in atopic eczema trials. Systematic reviews to identify adequate outcome measurement instruments for the other core outcome domains are underway. Clinical signs should be assessed in all atopic eczema trials by at least the Eczema Area and Severity Index. Quality of life, symptoms, and flares should also be assessed in all atopic eczema trials by a valid, reliable, and feasible instrument.

Time-dependent influence of sensorimotor set on automatic responses in perturbed stance

NASA Technical Reports Server (NTRS)

Chong, R. K.; Horak, F. B.; Woollacott, M. H.; Peterson, B. W. (Principal Investigator)

1999-01-01

These experiments tested the hypothesis that the ability to change sensorimotor set quickly for automatic responses depends on the time interval between successive surface perturbations. Sensorimotor set refers to the influence of prior experience or context on the state of the sensorimotor system. Sensorimotor set for postural responses was influenced by first giving subjects a block of identical backward translations of the support surface, causing forward sway and automatic gastrocnemius responses. The ability to change set quickly was inferred by measuring the suppression of the stretched antagonist gastrocnemius responses to toes-up rotations causing backward sway, following the translations. Responses were examined under short (10-14 s) and long (19-24 s) inter-trial intervals in young healthy subjects. The results showed that subjects in the long-interval group changed set immediately by suppressing gastrocnemius to 51% of translation responses within the first rotation and continued to suppress them over succeeding rotations. In contrast, subjects in the short-interval group did not change set immediately, but required two or more rotations to suppress gastrocnemius responses. By the last rotation, the short-interval group suppressed gastrocnemius responses to 33%, similar to the long-interval group of 29%. Associated surface plantarflexor torque resulting from these responses showed similar results. When rotation and translation perturbations alternated, however, the short-interval group was not able to suppress gastrocnemius responses to rotations as much as the long-interval group, although they did suppress more than in the first rotation trial after a series of translations. Set for automatic responses appears to linger, from one trial to the next. Specifically, sensorimotor set is more difficult to change when surface perturbations are given in close succession, making it appear as if set has become progressively stronger. A strong set does not mean that responses become larger over consecutive trials. Rather, it is inferred by the extent of difficulty in changing a response when it is appropriate to do so. These results suggest that the ability to change sensorimotor set quickly is sensitive to whether the change is required after a long or a short series of a prior different response, which in turn depends on the time interval between successive trials. Different rate of gastrocnemius suppression to toes-up rotation of the support surface have been reported in previous studies. This may be partially explained by different inter-trial time intervals demonstrated in this study.

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.

The Effectiveness of Parent Training as a Treatment for Preschool Attention-Deficit/Hyperactivity Disorder: Study Protocol for a Randomized Controlled, Multicenter Trial of the New Forest Parenting Program in Everyday Clinical Practice

PubMed Central

Daley, David; Frydenberg, Morten; Rask, Charlotte U; Sonuga-Barke, Edmund; Thomsen, Per H

2016-01-01

Background Parent training is recommended as the first-line treatment for attention-deficit/hyperactivity disorder (ADHD) in preschool children. The New Forest Parenting Programme (NFPP) is an evidence-based parenting program developed specifically to target preschool ADHD. Objective The objective of this trial is to investigate whether the NFPP can be effectively delivered for children referred through official community pathways in everyday clinical practice. Methods A multicenter randomized controlled parallel arm trial design is employed. There are two treatment arms, NFPP and treatment as usual. NFPP consists of eight individually delivered parenting sessions, where the child attends during three of the sessions. Outcomes are examined at three time points (T1, T2, T3): T1 (baseline), T2 (week 12, post intervention), and T3 (6 month follow/up). 140 children between the ages of 3-7, with a clinical diagnosis of ADHD, informed by the Development and Well Being Assessment, and recruited from three child and adolescent psychiatry departments in Denmark will take part. Randomization is on a 1:1 basis, stratified for age and gender. Results The primary endpoint is change in ADHD symptoms as measured by the Preschool ADHD-Rating Scale (ADHD-RS) by T2. Secondary outcome measures include: effects on this measure at T3 and T2 and T3 measures of teacher reported Preschool ADHD-RS scores, parent and teacher rated scores on the Strength & Difficulties Questionnaire, direct observation of ADHD behaviors during Child’s Solo Play, observation of parent-child interaction, parent sense of competence, and family stress. Results will be reported using the standards set out in the Consolidated Standards of Reporting Trials Statement for Randomized Controlled Trials of nonpharmacological treatments. Conclusions The trial will provide evidence as to whether NFPP is a more effective treatment for preschool ADHD than the treatment usually offered in everyday clinical practice. Trial Registration ClinicalTrials.gov NCT01684644; https://clinicaltrials.gov/ct2/show/NCT01684644?term= NCT01684644&rank=1 (Archived by WebCite at http://www.webcitation/6eOOAe8Qe) PMID:27076496

Stereochemical analysis of (+)-limonene using theoretical and experimental NMR and chiroptical data

NASA Astrophysics Data System (ADS)

Reinscheid, F.; Reinscheid, U. M.

2016-02-01

Using limonene as test molecule, the success and the limitations of three chiroptical methods (optical rotatory dispersion (ORD), electronic and vibrational circular dichroism, ECD and VCD) could be demonstrated. At quite low levels of theory (mpw1pw91/cc-pvdz, IEFPCM (integral equation formalism polarizable continuum model)) the experimental ORD values differ by less than 10 units from the calculated values. The modelling in the condensed phase still represents a challenge so that experimental NMR data were used to test for aggregation and solvent-solute interactions. After establishing a reasonable structural model, only the ECD spectra prediction showed a decisive dependence on the basis set: only augmented (in the case of Dunning's basis sets) or diffuse (in the case of Pople's basis sets) basis sets predicted the position and shape of the ECD bands correctly. Based on these result we propose a procedure to assign the absolute configuration (AC) of an unknown compound using the comparison between experimental and calculated chiroptical data.

First-principles investigation on Rydberg and resonance excitations: A case study of the firefly luciferin anion

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

Noguchi, Yoshifumi, E-mail: y.noguchi@issp.u-tokyo.ac.jp; Hiyama, Miyabi; Akiyama, Hidefumi

2014-07-28

The optical properties of an isolated firefly luciferin anion are investigated by using first-principles calculations, employing the many-body perturbation theory to take into account the excitonic effect. The calculated photoabsorption spectra are compared with the results obtained using the time-dependent density functional theory (TDDFT) employing the localized atomic orbital (AO) basis sets and a recent experiment in vacuum. The present method well reproduces the line shape at the photon energy corresponding to the Rydberg and resonance excitations but overestimates the peak positions by about 0.5 eV. However, the TDDFT-calculated positions of some peaks are closer to those of the experiment.more » We also investigate the basis set dependency in describing the free electron states above vacuum level and the excitons involving the transitions to the free electron states and conclude that AO-only basis sets are inaccurate for free electron states and the use of a plane wave basis set is required.« less

Citywide cluster randomized trial to restore blighted vacant land and its effects on violence, crime, and fear

Treesearch

Charles C. Branas; Eugenia South; Michelle C. Kondo; Bernadette C. Hohl; Philippe Bourgois; Douglas J. Wiebe; John M. MacDonald

2018-01-01

Vacant and blighted urban land is a widespread and potentially risky environmental condition encountered by millions of people on a daily basis. About 15% of the land in US cities is deemed vacant or abandoned, an area roughly the size of Switzerland. In a citywide cluster randomized controlled trial, we investigated the effects of standardized, reproducible...

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...

Biological Basis for Chemoprevention of Ovarian Cancer

DTIC Science & Technology

1999-10-01

potent apoptotic effect on ovarian epithelial cells, the use of levonorgestrel in chemoprevention of ovarian cancer is being explored in chickens and...women. A chemoprevention trial is ongoing in chickens and we will begin a trial to determine whether levonorgestrel induces apoptosis in the ovarian...subsequent studies performed in vitro, we have induced apoptosis in epithelial cells treated with the progestin levonorgestrel . Progestin mediated apoptotic

Design of Phase II Non-inferiority Trials.

PubMed

Jung, Sin-Ho

2017-09-01

With the development of inexpensive treatment regimens and less invasive surgical procedures, we are confronted with non-inferiority study objectives. A non-inferiority phase III trial requires a roughly four times larger sample size than that of a similar standard superiority trial. Because of the large required sample size, we often face feasibility issues to open a non-inferiority trial. Furthermore, due to lack of phase II non-inferiority trial design methods, we do not have an opportunity to investigate the efficacy of the experimental therapy through a phase II trial. As a result, we often fail to open a non-inferiority phase III trial and a large number of non-inferiority clinical questions still remain unanswered. In this paper, we want to develop some designs for non-inferiority randomized phase II trials with feasible sample sizes. At first, we review a design method for non-inferiority phase III trials. Subsequently, we propose three different designs for non-inferiority phase II trials that can be used under different settings. Each method is demonstrated with examples. Each of the proposed design methods is shown to require a reasonable sample size for non-inferiority phase II trials. The three different non-inferiority phase II trial designs are used under different settings, but require similar sample sizes that are typical for phase II trials.

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

Basis set study of classical rotor lattice dynamics.

PubMed

Witkoskie, James B; Wu, Jianlan; Cao, Jianshu

2004-03-22

The reorientational relaxation of molecular systems is important in many phenomenon and applications. In this paper, we explore the reorientational relaxation of a model Brownian rotor lattice system with short range interactions in both the high and low temperature regimes. In this study, we use a basis set expansion to capture collective motions of the system. The single particle basis set is used in the high temperature regime, while the spin wave basis is used in the low temperature regime. The equations of motion derived in this approach are analogous to the generalized Langevin equation, but the equations render flexibility by allowing nonequilibrium initial conditions. This calculation shows that the choice of projection operators in the generalized Langevin equation (GLE) approach corresponds to defining a specific inner-product space, and this inner-product space should be chosen to reveal the important physics of the problem. The basis set approach corresponds to an inner-product and projection operator that maintain the orthogonality of the spherical harmonics and provide a convenient platform for analyzing GLE expansions. The results compare favorably with numerical simulations, and the formalism is easily extended to more complex systems. (c) 2004 American Institute of Physics

Continuous support for women during childbirth.

PubMed

Bohren, Meghan A; Hofmeyr, G Justus; Sakala, Carol; Fukuzawa, Rieko K; Cuthbert, Anna

2017-07-06

Historically, women have generally been attended and supported by other women during labour. However, in hospitals worldwide, continuous support during labour has often become the exception rather than the routine. The primary objective was to assess the effects, on women and their babies, of continuous, one-to-one intrapartum support compared with usual care, in any setting. Secondary objectives were to determine whether the effects of continuous support are influenced by:1. Routine practices and policies in the birth environment that may affect a woman's autonomy, freedom of movement and ability to cope with labour, including: policies about the presence of support people of the woman's own choosing; epidural analgesia; and continuous electronic fetal monitoring.2. The provider's relationship to the woman and to the facility: staff member of the facility (and thus has additional loyalties or responsibilities); not a staff member and not part of the woman's social network (present solely for the purpose of providing continuous support, e.g. a doula); or a person chosen by the woman from family members and friends;3. Timing of onset (early or later in labour);4. Model of support (support provided only around the time of childbirth or extended to include support during the antenatal and postpartum periods);5. Country income level (high-income compared to low- and middle-income). We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2016), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (1 June 2017) and reference lists of retrieved studies. All published and unpublished randomised controlled trials, cluster-randomised trials comparing continuous support during labour with usual care. Quasi-randomised and cross-over designs were not eligible for inclusion. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We sought additional information from the trial authors. The quality of the evidence was assessed using the GRADE approach. We included a total of 27 trials, and 26 trials involving 15,858 women provided usable outcome data for analysis. These trials were conducted in 17 different countries: 13 trials were conducted in high-income settings; 13 trials in middle-income settings; and no studies in low-income settings. Women allocated to continuous support were more likely to have a spontaneous vaginal birth (average RR 1.08, 95% confidence interval (CI) 1.04 to 1.12; 21 trials, 14,369 women; low-quality evidence) and less likely to report negative ratings of or feelings about their childbirth experience (average RR 0.69, 95% CI 0.59 to 0.79; 11 trials, 11,133 women; low-quality evidence) and to use any intrapartum analgesia (average RR 0.90, 95% CI 0.84 to 0.96; 15 trials, 12,433 women). In addition, their labours were shorter (MD -0.69 hours, 95% CI -1.04 to -0.34; 13 trials, 5429 women; low-quality evidence), they were less likely to have a caesarean birth (average RR 0.75, 95% CI 0.64 to 0.88; 24 trials, 15,347 women; low-quality evidence) or instrumental vaginal birth (RR 0.90, 95% CI 0.85 to 0.96; 19 trials, 14,118 women), regional analgesia (average RR 0.93, 95% CI 0.88 to 0.99; 9 trials, 11,444 women), or a baby with a low five-minute Apgar score (RR 0.62, 95% CI 0.46 to 0.85; 14 trials, 12,615 women). Data from two trials for postpartum depression were not combined due to differences in women, hospitals and care providers included; both trials found fewer women developed depressive symptomatology if they had been supported in birth, although this may have been a chance result in one of the studies (low-quality evidence). There was no apparent impact on other intrapartum interventions, maternal or neonatal complications, such as admission to special care nursery (average RR 0.97, 95% CI 0.76 to 1.25; 7 trials, 8897 women; low-quality evidence), and exclusive or any breastfeeding at any time point (average RR 1.05, 95% CI 0.96 to 1.16; 4 trials, 5584 women; low-quality evidence).Subgroup analyses suggested that continuous support was most effective at reducing caesarean birth, when the provider was present in a doula role, and in settings in which epidural analgesia was not routinely available. Continuous labour support in settings where women were not permitted to have companions of their choosing with them in labour, was associated with greater likelihood of spontaneous vaginal birth and lower likelihood of a caesarean birth. Subgroup analysis of trials conducted in high-income compared with trials in middle-income countries suggests that continuous labour support offers similar benefits to women and babies for most outcomes, with the exception of caesarean birth, where studies from middle-income countries showed a larger reduction in caesarean birth. No conclusions could be drawn about low-income settings, electronic fetal monitoring, the timing of onset of continuous support or model of support.Risk of bias varied in included studies: no study clearly blinded women and personnel; only one study sufficiently blinded outcome assessors. All other domains were of varying degrees of risk of bias. The quality of evidence was downgraded for lack of blinding in studies and other limitations in study designs, inconsistency, or imprecision of effect estimates. Continuous support during labour may improve outcomes for women and infants, including increased spontaneous vaginal birth, shorter duration of labour, and decreased caesarean birth, instrumental vaginal birth, use of any analgesia, use of regional analgesia, low five-minute Apgar score and negative feelings about childbirth experiences. We found no evidence of harms of continuous labour support. Subgroup analyses should be interpreted with caution, and considered as exploratory and hypothesis-generating, but evidence suggests continuous support with certain provider characteristics, in settings where epidural analgesia was not routinely available, in settings where women were not permitted to have companions of their choosing in labour, and in middle-income country settings, may have a favourable impact on outcomes such as caesarean birth. Future research on continuous support during labour could focus on longer-term outcomes (breastfeeding, mother-infant interactions, postpartum depression, self-esteem, difficulty mothering) and include more woman-centred outcomes in low-income settings.

Feasibility of a blended group treatment (bGT) for major depression: uncontrolled interventional study in a university setting

PubMed Central

Fichtenbauer, Isabelle; Sparr, Verena Maria; Laireiter, Anton-Rupert

2018-01-01

Objective This study investigated the feasibility of a novel blended (face-to-face and computer-based) group intervention for the reduction of depressive symptoms in major depression. Design Patient-centred uncontrolled interventional study. Setting University setting in a general community sample. A multimodal recruitment strategy (public health centres and public areas) was applied. Participants Based on independent interviews, 26 participants, diagnosed with major depressive disorder (81% female; 23% comorbidity >1 and 23% comorbidity >2), entered treatment. Intervention Acceptance and mindfulness based, as well as self-management and resource-oriented psychotherapy principles served as the theoretical basis for the low-threshold intervention. The blended format included face-to-face sessions, complemented with multimedia presentations and a platform featuring videos, online work sheets, an unguided group chat and remote therapist–patient communication. Main outcome measures The Center for Epidemiological Studies-Depression scale and the 12-item General Health Questionnaire. Results Large to very large within group effect sizes were found on self-reported depression (F (2, 46.37)=25.69, p<0.001; d=1.80), general health (F (2,46.73)=11.47, p<0.001; d=1.32), personal resources (F (2,43.36)=21.17, p<0.001; d=0.90) and mindfulness (F (2,46.22)=9.40, p<0.001; d=1.12) after a follow-up period of 3 months. Treatment satisfaction was high, and 69% ranked computer and multimedia use as a therapeutic factor. Furthermore, participants described treatment intensification as important advantage of the blended format. Half of the patients (48%) would have preferred more time for personal exchange. Conclusion The investigated blended group format seems feasible for the reduction of depressive symptoms in major depression. The development of blended interventions can benefit from assuring that highly structured treatments actually meet patients’ needs. As a next step, the intervention should be tested in comparative trials in routine care. Trial registration number DRKS00010894; Pre-results. PMID:29530905

Two aspects of feedforward postural control: anticipatory postural adjustments and anticipatory synergy adjustments.

PubMed

Klous, Miriam; Mikulic, Pavle; Latash, Mark L

2011-05-01

We used the framework of the uncontrolled manifold hypothesis to explore the relations between anticipatory synergy adjustments (ASAs) and anticipatory postural adjustments (APAs) during feedforward control of vertical posture. ASAs represent a drop in the index of a multimuscle-mode synergy stabilizing the coordinate of the center of pressure in preparation to an action. ASAs reflect early changes of an index of covariation among variables reflecting muscle activation, whereas APAs reflect early changes in muscle activation levels averaged across trials. The assumed purpose of ASAs is to modify stability of performance variables, whereas the purpose of APAs is to change magnitudes of those variables. We hypothesized that ASAs would be seen before APAs and that this finding would be consistent with regard to the muscle-mode composition defined on the basis of different tasks and phases of action. Subjects performed a voluntary body sway task and a quick, bilateral shoulder flexion task under self-paced and reaction time conditions. Surface muscle activity of 12 leg and trunk muscles was analyzed to identify sets of 4 muscle modes for each task and for different phases within the shoulder flexion task. Variance components in the muscle-mode space and indexes of multimuscle-mode synergy stabilizing shift of the center of pressure were computed. ASAs were seen ∼ 100-150 ms prior to the task initiation, before APAs. The results were consistent with respect to different sets of muscle modes defined over the two tasks and different shoulder flexion phases. We conclude that the preparation for a self-triggered postural perturbation is associated with two types of anticipatory adjustments, ASAs and APAs. They reflect different feedforward processes within the hypothetical hierarchical control scheme, resulting in changes in patterns of covariation of elemental variables and in their patterns averaged across trials, respectively. The results show that synergies quantified using dissimilar sets of muscle modes show similar feedforward changes in preparation to action.

Theoretical study of the XP3 (X = Al, B, Ga) clusters

NASA Astrophysics Data System (ADS)

Ueno, Leonardo T.; Lopes, Cinara; Malaspina, Thaciana; Roberto-Neto, Orlando; Canuto, Sylvio; Machado, Francisco B. C.

2012-05-01

The lowest singlet and triplet states of AlP3, GaP3 and BP3 molecules with Cs, C2v and C3v symmetries were characterized using the B3LYP functional and the aug-cc-pVTZ and aug-cc-pVQZ correlated consistent basis sets. Geometrical parameters and vibrational frequencies were calculated and compared to existent experimental and theoretical data. Relative energies were obtained with single point CCSD(T) calculations using the aug-cc-pVTZ, aug-cc-pVQZ and aug-cc-pV5Z basis sets, and then extrapolating to the complete basis set (CBS) limit.

Establishing a successful clinical research program.

PubMed

Scoglio, Daniele; Fichera, Alessandro

2014-06-01

Clinical research (CR) is a natural corollary to clinical surgery. It gives an investigator the opportunity to critically review their results and develop new strategies. This article covers the critical factors and the important components of a successful CR program. The first and most important step is to build a dedicated research team to overcome time constraints and enable a surgical practice to make CR a priority. With the research team in place, the next step is to create a program on the basis of an original idea and new clinical hypotheses. This often comes from personal experience supported by a review of the available evidence. Randomized controlled (clinical) trials are the most stringent way of determining whether a cause-effect relationship exists between the intervention and the outcome. In the proper setting, translational research may offer additional avenues allowing clinical application of basic science discoveries.

How to compute isomerization energies of organic molecules with quantum chemical methods.

PubMed

Grimme, Stefan; Steinmetz, Marc; Korth, Martin

2007-03-16

The reaction energies for 34 typical organic isomerizations including oxygen and nitrogen heteroatoms are investigated with modern quantum chemical methods that have the perspective of also being applicable to large systems. The experimental reaction enthalpies are corrected for vibrational and thermal effects, and the thus derived "experimental" reaction energies are compared to corresponding theoretical data. A series of standard AO basis sets in combination with second-order perturbation theory (MP2, SCS-MP2), conventional density functionals (e.g., PBE, TPSS, B3-LYP, MPW1K, BMK), and new perturbative functionals (B2-PLYP, mPW2-PLYP) are tested. In three cases, obvious errors of the experimental values could be detected, and accurate coupled-cluster [CCSD(T)] reference values have been used instead. It is found that only triple-zeta quality AO basis sets provide results close enough to the basis set limit and that sets like the popular 6-31G(d) should be avoided in accurate work. Augmentation of small basis sets with diffuse functions has a notable effect in B3-LYP calculations that is attributed to intramolecular basis set superposition error and covers basic deficiencies of the functional. The new methods based on perturbation theory (SCS-MP2, X2-PLYP) are found to be clearly superior to many other approaches; that is, they provide mean absolute deviations of less than 1.2 kcal mol-1 and only a few (<10%) outliers. The best performance in the group of conventional functionals is found for the highly parametrized BMK hybrid meta-GGA. Contrary to accepted opinion, hybrid density functionals offer no real advantage over simple GGAs. For reasonably large AO basis sets, results of poor quality are obtained with the popular B3-LYP functional that cannot be recommended for thermochemical applications in organic chemistry. The results of this study are complementary to often used benchmarks based on atomization energies and should guide chemists in their search for accurate and efficient computational thermochemistry methods.

Comment on “Rethinking first-principles electron transport theories with projection operators: The problems caused by partitioning the basis set” [J. Chem. Phys. 139, 114104 (2013)

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

Brandbyge, Mads, E-mail: mads.brandbyge@nanotech.dtu.dk

2014-05-07

In a recent paper Reuter and Harrison [J. Chem. Phys. 139, 114104 (2013)] question the widely used mean-field electron transport theories, which employ nonorthogonal localized basis sets. They claim these can violate an “implicit decoupling assumption,” leading to wrong results for the current, different from what would be obtained by using an orthogonal basis, and dividing surfaces defined in real-space. We argue that this assumption is not required to be fulfilled to get exact results. We show how the current/transmission calculated by the standard Greens function method is independent of whether or not the chosen basis set is nonorthogonal, andmore » that the current for a given basis set is consistent with divisions in real space. The ambiguity known from charge population analysis for nonorthogonal bases does not carry over to calculations of charge flux.« less

Trial-to-Trial Carryover in Auditory Short-Term Memory

ERIC Educational Resources Information Center

Visscher, Kristina M.; Kahana, Michael J.; Sekuler, Robert

2009-01-01

Using a short-term recognition memory task, the authors evaluated the carryover across trials of 2 types of auditory information: the characteristics of individual study sounds (item information) and the relationships between the study sounds (study set homogeneity). On each trial, subjects heard 2 successive broadband study sounds and then…

Classroom Application of a Trial-Based Functional Analysis

ERIC Educational Resources Information Center

Bloom, Sarah E.; Iwata, Brian A.; Fritz, Jennifer N.; Roscoe, Eileen M.; Carreau, Abbey B.

2011-01-01

We evaluated a trial-based approach to conducting functional analyses in classroom settings. Ten students referred for problem behavior were exposed to a series of assessment trials, which were interspersed among classroom activities throughout the day. Results of these trial-based functional analyses were compared to those of more traditional…

Protocol for the development of a Core Outcome Set (COS) for hemorrhoidal disease: an international Delphi study.

PubMed

van Tol, R R; Melenhorst, J; Dirksen, C D; Stassen, L P S; Breukink, S O

2017-07-01

Over the last decade, many studies were performed regarding treatment options for hemorrhoidal disease. Randomised controlled trials (RCTs) should have well-defined primary and secondary outcomes. However, the reported outcome measures are numerous and diverse. The heterogeneity of outcome definition in clinical trials limits transparency and paves the way for bias. The development of a core outcome set (COS) helps minimizing this problem. A COS is an agreed minimum set of outcomes that should be measured and reported in all clinical trials of a specific disease. The aim of this project is to generate a COS regarding the outcome of treatment after hemorrhoidal disease. A Delphi study will be performed by an international steering group healthcare professionals and patients with the intention to create a standard outcome set for future clinical trials for the treatment of hemorrhoidal disease. First, a literature review will be conducted to establish which outcomes are used in clinical trials for hemorrhoidal disease. Secondly, both healthcare professionals and patients will participate in several consecutive rounds of online questionnaires and a face-to-face meeting to refine the content of the COS. Development of a COS for hemorrhoidal disease defines a minimum outcome-reporting standard and will improve the quality of research in the future.

Development of a core outcome set for disease modification trials in mild to moderate dementia: a systematic review, patient and public consultation and consensus recommendations.

PubMed Central

Webster, Lucy; Groskreutz, Derek; Grinbergs-Saull, Anna; Howard, Rob; O'Brien, John T; Mountain, Gail; Banerjee, Sube; Woods, Bob; Perneczky, Robert; Lafortune, Louise; Roberts, Charlotte; McCleery, Jenny; Pickett, James; Bunn, Frances; Challis, David; Charlesworth, Georgina; Featherstone, Katie; Fox, Chris; Goodman, Claire; Jones, Roy; Lamb, Sallie; Moniz-Cook, Esme; Schneider, Justine; Shepperd, Sasha; Surr, Claire; Thompson-Coon, Jo; Ballard, Clive; Brayne, Carol; Burke, Orlaith; Burns, Alistair; Clare, Linda; Garrard, Peter; Kehoe, Patrick; Passmore, Peter; Holmes, Clive; Maidment, Ian; Murtagh, Fliss; Robinson, Louise; Livingston, Gill

2017-01-01

BACKGROUND There is currently no disease-modifying treatment available to halt or delay the progression of the disease pathology in dementia. An agreed core set of the best-available and most appropriate outcomes for disease modification would facilitate the design of trials and ensure consistency across disease modification trials, as well as making results comparable and meta-analysable in future trials. OBJECTIVES To agree a set of core outcomes for disease modification trials for mild to moderate dementia with the UK dementia research community and patient and public involvement (PPI). DATA SOURCES We included disease modification trials with quantitative outcomes of efficacy from (1) references from related systematic reviews in workstream 1; (2) searches of the Cochrane Dementia and Cognitive Improvement Group study register, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Latin American and Caribbean Health Sciences Literature and PsycINFO on 11 December 2015, and clinical trial registries [International Standard Randomised Controlled Trial Number (ISRCTN) and clinicaltrials.gov] on 22 and 29 January 2016; and (3) hand-searches of reference lists of relevant systematic reviews from database searches. REVIEW METHODS The project consisted of four workstreams. (1) We obtained related core outcome sets and work from co-applicants. (2) We systematically reviewed published and ongoing disease modification trials to identify the outcomes used in different domains. We extracted outcomes used in each trial, recording how many used each outcome and with how many participants. We divided outcomes into the domains measured and searched for validation data. (3) We consulted with PPI participants about recommended outcomes. (4) We presented all the synthesised information at a conference attended by the wider body of National Institute for Health Research (NIHR) dementia researchers to reach consensus on a core set of outcomes. RESULTS We included 149 papers from the 22,918 papers screened, referring to 125 individual trials. Eighty-one outcomes were used across trials, including 72 scales [31 cognitive, 12 activities of daily living (ADLs), 10 global, 16 neuropsychiatric and three quality of life] and nine biological techniques. We consulted with 18 people for PPI. The conference decided that only cognition and biological markers are core measures of disease modification. Cognition should be measured by the Mini Mental State Examination (MMSE) or the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog), and brain changes through structural magnetic resonance imaging (MRI) in a subset of participants. All other domains are important but not core. We recommend using the Neuropsychiatric Inventory for neuropsychiatric symptoms: the Disability Assessment for Dementia for ADLs, the Dementia Quality of Life Measure for quality of life and the Clinical Dementia Rating scale to measure dementia globally. LIMITATIONS Most of the trials included participants with Alzheimer's disease, so recommendations may not apply to other types of dementia. We did not conduct economic analyses. The PPI consultation was limited to members of the Alzheimer's Society Research Network. CONCLUSIONS Cognitive outcomes and biological markers form the core outcome set for future disease modification trials, measured by the MMSE or ADAS-Cog, and structural MRI in a subset of participants. FUTURE WORK We envisage that the core set may be superseded in the future, particularly for other types of dementia. There is a need to develop an algorithm to compare scores on the MMSE and ADAS-Cog. STUDY REGISTRATION The project was registered with Core Outcome Measures in Effectiveness Trials [ www.comet-initiative.org/studies/details/819?result=true (accessed 7 April 2016)]. The systematic review protocol is registered as PROSPERO CRD42015027346. FUNDING The National Institute for Health Research Health Technology Assessment programme. PMID:28625273

Some considerations about Gaussian basis sets for electric property calculations

NASA Astrophysics Data System (ADS)

Arruda, Priscilla M.; Canal Neto, A.; Jorge, F. E.

Recently, segmented contracted basis sets of double, triple, and quadruple zeta valence quality plus polarization functions (XZP, X = D, T, and Q, respectively) for the atoms from H to Ar were reported. In this work, with the objective of having a better description of polarizabilities, the QZP set was augmented with diffuse (s and p symmetries) and polarization (p, d, f, and g symmetries) functions that were chosen to maximize the mean dipole polarizability at the UHF and UMP2 levels, respectively. At the HF and B3LYP levels of theory, electric dipole moment and static polarizability for a sample of molecules were evaluated. Comparison with experimental data and results obtained with a similar size basis set, whose diffuse functions were optimized for the ground state energy of the anion, was done.

Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial

PubMed Central

Aga, Anna-Birgitte; Olsen, Inge Christoffer; Lillegraven, Siri; Hammer, Hilde B; Uhlig, Till; Fremstad, Hallvard; Madland, Tor Magne; Lexberg, Åse Stavland; Haukeland, Hilde; Rødevand, Erik; Høili, Christian; Stray, Hilde; Noraas, Anne; Hansen, Inger Johanne Widding; Bakland, Gunnstein; Nordberg, Lena Bugge; van der Heijde, Désirée; Kvien, Tore K

2016-01-01

Objective To determine whether a treatment strategy based on structured ultrasound assessment would lead to improved outcomes in rheumatoid arthritis, compared with a conventional strategy. Design Multicentre, open label, two arm, parallel group, randomised controlled strategy trial. Setting Ten rheumatology departments and one specialist centre in Norway, from September 2010 to September 2015. Participants 238 patients were recruited between September 2010 and April 2013, of which 230 (141 (61%) female) received the allocated intervention and were analysed for the primary outcome. The main inclusion criteria were age 18-75 years, fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis, disease modifying anti-rheumatic drug naivety with indication for disease modifying drug therapy, and time from first patient reported swollen joint less than two years. Patients with abnormal kidney or liver function or major comorbidities were excluded. Interventions 122 patients were randomised to an ultrasound tight control strategy targeting clinical and imaging remission, and 116 patients were randomised to a conventional tight control strategy targeting clinical remission. Patients in both arms were treated according to the same disease modifying anti-rheumatic drug escalation strategy, with 13 visits over two years. Main outcome measures The primary endpoint was the proportion of patients with a combination between 16 and 24 months of clinical remission, no swollen joints, and non-progression of radiographic joint damage. Secondary outcomes included measures of disease activity, radiographic progression, functioning, quality of life, and adverse events. All participants who attended at least one follow-up visit were included in the full analysis set. Results 26 (22%) of the 118 analysed patients in the ultrasound tight control arm and 21 (19%) of the 112 analysed patients in the clinical tight control arm reached the primary endpoint (mean difference 3.3%, 95% confidence interval −7.1% to 13.7%). Secondary endpoints (disease activity, physical function, and joint damage) were similar between the two groups. Six (5%) patients in the ultrasound tight control arm and seven (6%) patients in the conventional arm had serious adverse events. Conclusions The systematic use of ultrasound in the follow-up of patients with early rheumatoid arthritis treated according to current recommendations is not justified on the basis of the ARCTIC results. The findings highlight the need for randomised trials assessing the clinical application of medical technology. Trial registration Clinical trials NCT01205854. PMID:27530741

Outdoor Biology Instructional Strategies Trial Edition, Set IV.

ERIC Educational Resources Information Center

Throgmorton, Larry, Ed.; And Others

Eight games are included in the 24 activities in the Outdoor Biology Instructional Strategies (OBIS) Trial Edition Set IV. There are also simulations, crafts, biological techniques, and organism investigations focusing on animal and plant life in the forest, desert, and snow. Designed for small groups of children ages 10 to 15 from schools and…

Health Activities Project (HAP), Trial Edition III.

ERIC Educational Resources Information Center

Buller, Dave; And Others

Contained within this Health Activities Project (HAP) trial edition (set III) are a teacher information folio and numerous student activity folios which center around the idea that students in grades 5-8 can control their own health and safety. Each student folio is organized into an Overview, Health Background, Materials, Setting Up, and…

Health Activities Project (HAP), Trial Edition II.

ERIC Educational Resources Information Center

Buller, Dave; And Others

Contained within this Health Activities Project (HAP) trial edition (set II) are a teacher information folio and numerous student activity folios which center around the idea that students in grades 5-8 can control their own health and safety. Each student folio is organized into a Synopsis, Health Background, Materials, Setting Up, and Activities…

The Education of Juveniles in Detention: Policy Considerations and Infrastructure Development

ERIC Educational Resources Information Center

Geib, Catherine Foley; Chapman, John F.; D'Amaddio, Amy H.; Grigorenko, Elena L.

2011-01-01

This article presents a discussion of the state of affairs pertaining to educating juvenile justice-involved youth. It summarizes general observations regarding the schooling of juveniles in pre-trial and post-trial incarceration settings, as well as, juveniles on probation or in community settings. The article selectively presents relevant…

Developing core outcome sets for clinical trials: issues to consider

PubMed Central

2012-01-01

The selection of appropriate outcomes or domains is crucial when designing clinical trials in order to compare directly the effects of different interventions in ways that minimize bias. If the findings are to influence policy and practice then the chosen outcomes need to be relevant and important to key stakeholders including patients and the public, health care professionals and others making decisions about health care. There is a growing recognition that insufficient attention has been paid to the outcomes measured in clinical trials. These issues could be addressed through the development and use of an agreed standardized collection of outcomes, known as a core outcome set, which should be measured and reported, as a minimum, in all trials for a specific clinical area. Accumulating work in this area has identified the need for general guidance on the development of core outcome sets. Key issues to consider in the development of a core outcome set include its scope, the stakeholder groups to involve, choice of consensus method and the achievement of a consensus. PMID:22867278

Overcoming residual interference in mental set switching: Neural correlates and developmental trajectory

PubMed Central

Witt, Suzanne T.; Stevens, Michael C.

2012-01-01

Mental set switching is a key facet of executive control measured behaviorally through reaction time or accuracy (i.e., ‘switch costs’) when shifting among task types. One of several experimentally-dissociable influences on switch costs is ‘task set inertia’, conceptualized as the residual interference conferred when a previous stimulus-response tendency interferes with subsequent stimulus processing on a new task. Task set inertia is thought to represent the passive decay of the previous stimulus-response set from working memory, and its effects decrease with increased interstimulus interval. Closely spaced trials confer high task set inertia, while sparsely spaced trials confer low task set inertia. This functional magnetic resonance imaging (fMRI) study characterized, for the first time, two opposing brain systems engaged to resolve task set inertia: 1) a frontoparietal ‘cortical control’ network for overcoming high task set inertia interference and 2) a subcortical-motor network more active during trials with low task set inertia. These networks were distinct from brain regions showing general switching effects (i.e., switch > non-switch) and from other previously-characterized interference effects. Moreover, there were ongoing maturational effects throughout adolescence for the brain regions engaged to overcome high task set inertia not seen for generalized switching effects. These novel findings represent a new avenue of exploration of cognitive set switching neural function. PMID:22584223

Measures That Identify Prescription Medication Misuse, Abuse, and Related Events in Clinical Trials: ACTTION Critique and Recommended Considerations.

PubMed

Smith, Shannon M; Jones, Judith K; Katz, Nathaniel P; Roland, Carl L; Setnik, Beatrice; Trudeau, Jeremiah J; Wright, Stephen; Burke, Laurie B; Comer, Sandra D; Dart, Richard C; Dionne, Raymond; Haddox, J David; Jaffe, Jerome H; Kopecky, Ernest A; Martell, Bridget A; Montoya, Ivan D; Stanton, Marsha; Wasan, Ajay D; Turk, Dennis C; Dworkin, Robert H

2017-11-01

Accurate assessment of inappropriate medication use events (ie, misuse, abuse, and related events) occurring in clinical trials is an important component in evaluating a medication's abuse potential. A meeting was convened to review all instruments measuring such events in clinical trials according to previously published standardized terminology and definitions. Only 2 approaches have been reported that are specifically designed to identify and classify misuse, abuse, and related events occurring in clinical trials, rather than to measure an individual's risk of using a medication inappropriately: the Self-Reported Misuse, Abuse, and Diversion (SR-MAD) instrument and the Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS). The conceptual basis, strengths, and limitations of these methods are discussed. To our knowledge, MADDERS is the only system available to comprehensively evaluate inappropriate medication use events prospectively to determine the underlying intent. MADDERS can also be applied retrospectively to completed trial data. SR-MAD can be used prospectively; additional development may be required to standardize its implementation and fully appraise the intent of inappropriate use events. Additional research is needed to further demonstrate the validity and utility of MADDERS as well as SR-MAD. Identifying a medication's abuse potential requires assessing inappropriate medication use events in clinical trials on the basis of a standardized event classification system. The strengths and limitations of the 2 published methods designed to evaluate inappropriate medication use events are reviewed, with recommended considerations for further development and current implementation. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

A Simplified Approach to the Basis Functions of Symmetry Operations and Terms of Metal Complexes in an Octahedral Field with d[superscript 1] to d[superscript 9] Configurations

ERIC Educational Resources Information Center

Lee, Liangshiu

2010-01-01

The basis sets for symmetry operations of d[superscript 1] to d[superscript 9] complexes in an octahedral field and the resulting terms are derived for the ground states and spin-allowed excited states. The basis sets are of fundamental importance in group theory. This work addresses such a fundamental issue, and the results are pedagogically…

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

Makhov, Dmitry V.; Shalashilin, Dmitrii V.; Glover, William J.

We present a new algorithm for ab initio quantum nonadiabatic molecular dynamics that combines the best features of ab initio Multiple Spawning (AIMS) and Multiconfigurational Ehrenfest (MCE) methods. In this new method, ab initio multiple cloning (AIMC), the individual trajectory basis functions (TBFs) follow Ehrenfest equations of motion (as in MCE). However, the basis set is expanded (as in AIMS) when these TBFs become sufficiently mixed, preventing prolonged evolution on an averaged potential energy surface. We refer to the expansion of the basis set as “cloning,” in analogy to the “spawning” procedure in AIMS. This synthesis of AIMS and MCEmore » allows us to leverage the benefits of mean-field evolution during periods of strong nonadiabatic coupling while simultaneously avoiding mean-field artifacts in Ehrenfest dynamics. We explore the use of time-displaced basis sets, “trains,” as a means of expanding the basis set for little cost. We also introduce a new bra-ket averaged Taylor expansion (BAT) to approximate the necessary potential energy and nonadiabatic coupling matrix elements. The BAT approximation avoids the necessity of computing electronic structure information at intermediate points between TBFs, as is usually done in saddle-point approximations used in AIMS. The efficiency of AIMC is demonstrated on the nonradiative decay of the first excited state of ethylene. The AIMC method has been implemented within the AIMS-MOLPRO package, which was extended to include Ehrenfest basis functions.« less

Adrenaline (epinephrine) for the treatment of anaphylaxis with and without shock.

PubMed

Sheikh, Aziz; Shehata, Yasser A; Brown, Simon Ga; Simons, F Estelle R

2008-10-08

Anaphylaxis is a serious hypersensitivity reaction that is rapid in onset and may cause death. Adrenaline is recommended as the initial treatment of choice for anaphylaxis. To assess the benefits and harms of adrenaline (epinephrine) in the treatment of anaphylaxis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 1), MEDLINE (1966 to March 2007), EMBASE (1966 to March 2007), CINAHL (1982 to March 2007), BIOSIS (to March 2007), ISI Web of Knowledge (to March 2007) and LILACS (to March 2007). We also searched websites listing ongoing trials: http://clinicaltrials.gov/, http://www.controlledtrials.com and http://www.actr.org.au/; and contacted pharmaceutical companies and international experts in anaphylaxis in an attempt to locate unpublished material. Randomized and quasi-randomized controlled trials comparing adrenaline with no intervention, placebo or other adrenergic agonists were eligible for inclusion. Two authors independently assessed articles for inclusion. We found no studies that satisfied the inclusion criteria. Based on this review, we are unable to make any new recommendations on the use of adrenaline for the treatment of anaphylaxis. Although there is a need for randomized, double-blind, placebo-controlled clinical trials of high methodological quality in order to define the true extent of benefits from the administration of adrenaline in anaphylaxis, such trials are unlikely to be performed in individuals with anaphylaxis. Indeed, they might be unethical because prompt treatment with adrenaline is deemed to be critically important for survival in anaphylaxis. Also, such studies would be difficult to conduct because anaphylactic episodes usually occur without warning, often in a non-medical setting, and differ in severity both among individuals and from one episode to another in the same individual. Consequently, obtaining baseline measurements and frequent timed measurements might be difficult, or impossible, to obtain. In the absence of appropriate trials, we recommend, albeit on the basis of less than optimal evidence, that adrenaline administration by intramuscular (i.m.) injection should still be regarded as first-line treatment for the management of anaphylaxis.

[Real-world data on novel oral anticoagulants: the added value of registries and observational studies. Focus on apixaban].

PubMed

Pelliccia, Francesco; Tanzilli, Gaetano; Schiariti, Michele; Viceconte, Nicola; Greco, Cesare; Gaudio, Carlo

2016-12-01

Anticoagulant therapy has been used with great effect for decades for the prevention of stroke among patients with atrial fibrillation. In recent years, the therapeutic armamentarium has been strengthened considerably, with the addition of anticoagulants acting through novel pathways. The currently available novel agents are apixaban, rivaroxaban and dabigatran. These novel oral anticoagulants (NOACs) were approved for use on the basis of major clinical trials clearly demonstrating improved risk reductions compared to warfarin for stroke and/or major bleeding events. In these studies, apixaban and dabigatran 150 mg each significantly reduced the risk of stroke, while apixaban and dabigatran 110 mg reduced the risk of major bleeding compared to warfarin. Extrapolating the results of the randomized clinical trials on NOACs to all patients is not possible, as the strict design of clinical trials yields information that is directly applicable to a relatively narrow spectrum of patients. To control for confounding variables, randomized studies restrict enrolment to a prespecified set of criteria that do not necessarily reflect the profiles of all those who could potentially benefit from these agents. Research continues using the trial databases, in an attempt to better identify patient subgroups who do or do not benefit from each of the agents. At the European Society of Cardiology (ESC) annual meetings in London in 2015 and in Rome in 2016, there were several presentations and posters providing this type of evidence. Perhaps more important, as real-world experience with these agents grows, we are beginning to obtain meaningful new information about the NOACs in everyday use. This has involved the study of large databases including patients receiving these medications in clinical situations less stringently defined than in the randomized clinical trials. These include purpose-built registries, observational studies, and analyses of healthcare administrative databases. At both ESC meetings in 2015 and 2016, a wealth of information was presented using these types of sources. In many cases, these new data reinforce the key learnings from the randomized clinical trials. The following report provides highlights of registry and other post-marketing data presented at both ESC meetings in 2015 and 2016.

The effects of study task on prestimulus subsequent memory effects in the hippocampus.

PubMed

de Chastelaine, Marianne; Rugg, Michael D

2015-11-01

Functional magnetic resonance imaging (fMRI) was employed to examine the effects of a study task manipulation on pre-stimulus activity in the hippocampus predictive of later successful recollection. Eighteen young participants were scanned while making either animacy or syllable judgments on visually presented study words. Cues presented before each word denoted which judgment should be made. Following the study phase, a surprise recognition memory test was administered in which each test item had to be endorsed as "Remembered," "Known," or "New." As expected, "deep" animacy judgments led to better memory for study items than did "shallow" syllable judgments. In both study tasks, pre-stimulus subsequent recollection effects were evident in the interval between the cue and the study item in bilateral anterior hippocampus. However, the direction of the effects differed according to the study task: whereas pre-stimulus hippocampal activity on animacy trials was greater for later recollected items than items judged old on the basis of familiarity (replicating prior findings), these effects reversed for syllable trials. We propose that the direction of pre-stimulus hippocampal subsequent memory effects depends on whether an optimal pre-stimulus task set facilitates study processing that is conducive or unconducive to the formation of contextually rich episodic memories. © 2015 Wiley Periodicals, Inc.

Micronutrient powders to combat anaemia in young children: do they work?

PubMed

Verhoef, Hans; Teshome, Emily; Prentice, Andrew M

2018-01-22

In 2016, the World Health Organization (WHO) recommended point-of-use fortification of complementary foods with iron-containing micronutrient powders to improve iron status and reduce anaemia in children at risk of anaemia. This recommendation continues to be debated. In a recent trial among Kenyan children aged 12-36 months, we found no evidence that daily point-of-use fortification was efficacious in improving haemoglobin concentration or plasma iron markers. An updated meta-analysis indicated that, on average, in an arbitrarily selected setting and with adherence as obtained under trial conditions, one may expect a small increase in haemoglobin concentration in preschool children, with the upper limit of the 95% CI virtually excluding an effect beyond 5.5 g/L. In the present paper, we elaborate on the interpretation of these findings and the meta-analyses that formed the basis for the WHO guidelines. In particular, we draw attention to the phenomenon that small group differences in the distribution of continuous outcomes (haemoglobin concentration, ferritin concentrations) can give a false impression of relatively large effects on the prevalence of the dichotomised outcomes (anaemia, iron deficiency).Please see related articles: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0839-z , https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0867-8.

How are palliative care cancer populations characterized in randomized controlled trials? A literature review.

PubMed

Sigurdardottir, Katrin Ruth; Oldervoll, Line; Hjermstad, Marianne Jensen; Kaasa, Stein; Knudsen, Anne Kari; Løhre, Erik Torbjørn; Loge, Jon Håvard; Haugen, Dagny Faksvåg

2014-05-01

The difficulties in defining a palliative care patient accentuate the need to provide stringent descriptions of the patient population in palliative care research. To conduct a systematic literature review with the aim of identifying which key variables have been used to describe adult palliative care cancer populations in randomized controlled trials (RCTs). The data sources used were MEDLINE (1950 to January 25, 2010) and Embase (1980 to January 25, 2010), limited to RCTs in adult cancer patients with incurable disease. Forty-three variables were systematically extracted from the eligible articles. The review includes 336 articles reporting RCTs in palliative care cancer patients. Age (98%), gender (90%), cancer diagnosis (89%), performance status (45%), and survival (45%) were the most frequently reported variables. A large number of other variables were much less frequently reported. A substantial variation exists in how palliative care cancer populations are described in RCTs. Few variables are consistently registered and reported. There is a clear need to standardize the reporting. The results from this work will serve as the basis for an international Delphi process with the aim of reaching consensus on a minimum set of descriptors to characterize a palliative care cancer population. Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Use of Dried Capillary Blood Sampling for Islet Autoantibody Screening in Relatives: A Feasibility Study

PubMed Central

Rafkin, Lisa E.; Matheson, Della; Steck, Andrea K.; Yu, Liping; Henderson, Courtney; Beam, Craig A.; Boulware, David C.

2015-01-01

Abstract Background: Islet autoantibody testing provides the basis for assessment of risk of progression to type 1 diabetes. We set out to determine the feasibility and acceptability of dried capillary blood spot–based screening to identify islet autoantibody–positive relatives potentially eligible for inclusion in prevention trials. Materials and Methods: Dried blood spot (DBS) and venous samples were collected from 229 relatives participating in the TrialNet Pathway to Prevention Study. Both samples were tested for glutamic acid decarboxylase, islet antigen 2, and zinc transporter 8 autoantibodies, and venous samples were additionally tested for insulin autoantibodies and islet cell antibodies. We defined multiple autoantibody positive as two or more autoantibodies in venous serum and DBS screen positive if one or more autoantibodies were detected. Participant questionnaires compared the sample collection methods. Results: Of 44 relatives who were multiple autoantibody positive in venous samples, 42 (95.5%) were DBS screen positive, and DBS accurately detected 145 of 147 autoantibody-negative relatives (98.6%). Capillary blood sampling was perceived as more painful than venous blood draw, but 60% of participants would prefer initial screening using home fingerstick with clinic visits only required if autoantibodies were found. Conclusions: Capillary blood sampling could facilitate screening for type 1 diabetes prevention studies. PMID:26375197

Non-attendance at counselling therapy in cocaine-using methadone-maintained patients: lessons learnt from an abandoned randomised controlled trial.

PubMed

Darker, C; Sweeney, B; El Hassan, H; Kelly, A; O' Connor, S; Smyth, B; Barry, J

2012-12-01

Recently, the authors commenced a randomised controlled trial to study the effectiveness of cognitive behavioural coping skills (CBCS) to reduce cocaine usage in methadone-maintained patients' in a clinical setting by assessing attendance at treatment sessions and outcomes in terms of cocaine use. However, recruitment into the study stopped when it became apparent that attendance at counselling sessions was poor. The aim of the current study was to determine the reasons for both non-attendance and attendance from a patient's perspective at counselling sessions. A cross-sectional design was employed whereby participants who were recruited for the original study were interviewed utilising a semi-structured interview format. Motivational inconsistencies were most frequently cited as the reason for dropping out of counselling, whereas a good relationship with staff was cited by attenders as the most important factors which aided their attendance at counselling sessions. Selecting opiate-dependent methadone-maintained cocaine abusers on the basis of their urine toxicology and offering them counselling as a way of reducing their harmful drug use did not prove efficacious. Attempting to address cocaine misuse within this cohort may need a more stepped approach including brief interventions, such as motivational interviewing, or other enhancers of motivation before we can test the effectiveness of CBCS in this population.

Outcome of High-Risk Myelodysplastic Syndrome After Azacitidine Treatment Failure

PubMed Central

Prébet, Thomas; Gore, Steven D.; Esterni, Benjamin; Gardin, Claude; Itzykson, Raphael; Thepot, Sylvain; Dreyfus, François; Rauzy, Odile Beyne; Recher, Christian; Adès, Lionel; Quesnel, Bruno; Beach, C.L.; Fenaux, Pierre; Vey, Norbert

2011-01-01

Purpose Azacitidine (AZA) is the current standard of care for high-risk (ie, International Prognostic Scoring System high or intermediate 2) myelodysplastic syndrome (MDS), but most patients will experience primary or secondary treatment failure. The outcome of these patients has not yet been described. Patients and Methods Overall, 435 patients with high-risk MDS and former refractory anemia with excess blasts in transformation (RAEB-T) were evaluated for outcome after AZA failure. The cohort of patients included four data sets (ie, AZA001, J9950, and J0443 trials and the French compassionate use program). Results The median follow-up after AZA failure was 15 months. The median overall survival was 5.6 months, and the 2-year survival probability was 15%. Increasing age, male sex, high-risk cytogenetics, higher bone marrow blast count, and the absence of prior hematologic response to AZA were associated with significantly worse survival in multivariate analysis. Data on treatment administered after AZA failure were available for 270 patients. Allogeneic stem-cell transplantation and investigational agents were associated with a better outcome when compared with conventional clinical care. Conclusion Outcome after AZA failure is poor. Our results should serve as a basis for designing second-line clinical trials in this population. PMID:21788559

From Controlled Trial to Community Adoption: The Multisite Translational Community Trial

PubMed Central

Murimi, Mary; Gonzalez, Anjelica; Njike, Valentine; Green, Lawrence W.

2011-01-01

Methods for translating the findings of controlled trials, such as the Diabetes Prevention Program, into real-world community application have not been clearly defined. A standardized research methodology for making and evaluating such a transition is needed. We introduce the multisite translational community trial (mTCT) as the research analog to the multisite randomized controlled trial. The mTCT is adapted to incorporate the principles and practices of community-based participatory research and the increased relevance and generalizability gained from diverse community settings. The mTCT is a tool designed to bridge the gap between what a clinical trial demonstrates can work in principle and what is needed to make it workable and effective in real-world settings. Its utility could be put to the test, in particular with practice-based research networks such as the Prevention Research Centers. PMID:21680935

A survey of facilitators and barriers to recruitment to the MAGNETIC trial.

PubMed

Kaur, Geetinder; Smyth, Rosalind L; Powell, Colin V E; Williamson, Paula

2016-12-23

Recruitment to randomised controlled trials with children is challenging. It is imperative to understand the factors that boost or hinder recruitment of children to clinical trials. We conducted a survey of facilitators and barriers to recruitment to the MAGNETIC trial, using a previously developed web-based tool. MAGNETIC is a multicentre randomised trial of nebulised magnesium in acute severe asthma, recruiting 508 children from 30 UK sites. Recruiters were asked to grade a list of factors from -3 to +3 depending on whether the factor was perceived as a strong, intermediate or weak barrier (-3 to -1) or facilitator (+1 to + 3), and using (0) if it was thought to be not applicable. Free text responses were invited on strategies applied to counter the identified barriers. The commonly identified facilitators were motivation and experience of study teams, effective communication and coordination between teams at site and between sites and the Clinical Trials Unit, the presence of designated research nurses, good trial management, clinical trial publicity, simple inclusion criteria, effective communication with parents and presentation of trial information in a simple and clear manner. The commonly identified barriers were heavy clinical workload, shift patterns of work, Good Clinical Practice (GCP) training, inadequate number of trained staff, time and setting of consent seeking, non-availability of research staff out of hours and parents' concerns about their child taking an experimental medicine. Having a designated research nurse, arranging GCP training and trial-related training sessions for staff were the most commonly reported interventions. This study highlights important generic and trial-specific facilitators and barriers to recruitment to a paediatric trial in the acute setting and provides information on the recruitment strategies or interventions that were applied to overcome these barriers. This information can be very useful in informing the design and conduct of future clinical trials with children, particularly in the acute or emergency setting. ISRCTN, ISRCTN81456894 . Registered on 15 November 2007.

Interventions in sports settings to reduce risky alcohol consumption and alcohol-related harm: a systematic review.

PubMed

Kingsland, Melanie; Wiggers, John H; Vashum, Khanrin P; Hodder, Rebecca K; Wolfenden, Luke

2016-01-21

Elevated levels of risky alcohol consumption and alcohol-related harm have been reported for sportspeople and supporters compared to non-sporting populations. Limited systematic reviews have been conducted to assess the effect of interventions targeting such behaviours. A review was undertaken to determine if interventions implemented in sports settings decreased alcohol consumption and related harms. Studies were included that implemented interventions within sports settings; measured alcohol consumption or alcohol-related injury or violence and were either randomised controlled trials, staggered enrollment trials, stepped-wedged trials, quasi-randomised trials, quasi-experimental trials or natural experiments. Studies without a parallel comparison group were excluded. Studies from both published and grey literature were included. Two authors independently screened potential studies against the eligibility criteria, and two authors independently extracted data from included studies and assessed risk of bias. The results of included studies were synthesised narratively. The title and abstract of 6382 papers and the full text of 45 of these papers were screened for eligibility. Three studies met the inclusion criteria for the review. One of the included studies was a randomised controlled trial (RCT) of a cognitive-behavioural intervention with athletes within an Olympic training facility in the USA. The study reported a significant change in alcohol use between pre-test and follow-up between intervention and control groups. The other two studies were RCTs in community sports clubs in Ireland and Australia. The Australian study found a significant intervention effect for both risky alcohol consumption at sports clubs and overall risk of alcohol-related harm. The Irish study found no significant intervention effect. A limited number of studies have been conducted to assess the effect of interventions implemented in sports settings on alcohol consumption and related harms. While two of the three studies found significant intervention effects, it is difficult to determine the extent to which such effects are generalisable. Further controlled trials are required in this setting. PROSPERO CRD42014001739.

The Trial Using Motivational Interviewing and Positive Affect and Self-Affirmation in African-Americans with Hypertension (TRIUMPH): From Theory to Clinical Trial Implementation

PubMed Central

Boutin-Foster, Carla; Scott, Ebony; Rodriguez, Anna; Ramos, Rosio; Kanna, Balavenkatesh; Michelen, Walid; Charlson, Mary; Gbenga, Ogedegbe

2014-01-01

This paper describes the application of a translational research model in developing The Trial Using Motivational Interviewing and Positive Affect and Self-Affirmation in African-Americans with Hypertension (TRIUMPH), a theoretically-based, randomized controlled trial. TRIUMPH targets blood pressure control among African-Americans with hypertension in a community health center and public hospital setting. TRIUMPH applies positive affect, self-affirmation, and motivational interviewing as strategies to increase medication adherence and blood pressure control. A total of 220 participants were recruited in TRIUMPH and are currently being followed. This paper provides a detailed description of the theoretical framework and study design of TRIUMPH and concludes with a critical reflection of the lessons learned in the process of implementing a health behavior intervention in a community-based setting. TRIUMPH provides a model for incorporating the translational science research paradigm to conducting pragmatic behavioral trials in a real-world setting in a vulnerable population. Lessons learned through interactions with our community partners reinforce the value of community engagement in research. PMID:23403073

The system neurophysiological basis of backward inhibition.

PubMed

Zhang, Rui; Stock, Ann-Kathrin; Fischer, Rico; Beste, Christian

2016-12-01

Task switching is regularly required in our everyday life. To succeed in switching, it is important to inhibit the most recently performed task and instead activate the currently relevant task. The process that inhibits a recently performed task when a new task is to be performed is referred to as 'backward inhibition' (BI). While the BI effect has been subject to intense research in cognitive psychology, little is known about the neuronal mechanisms that are related to the BI effect and those that relate to differences in the magnitude of the BI effect. In the current study, we examined the system neurophysiological basis of BI processes using event-related potentials (ERPs) and sLORETA by also taking inter-individual differences in the magnitude of the BI into account. The results suggest that BI processes and inter-individual differences in them strongly depend upon attentional selection mechanisms (reflected by N1-ERP modulations in the current task/trial) mediated via networks consisting of extrastriate occipital areas, the temporo-parietal junction and the inferior frontal gyrus. Other processes and mechanisms related to conflict monitoring, response selection, or the updating, organization and implementation of a new task-set (i.e. N2 and P3 processes) were not shown to be modulated by BI processes and differences in their magnitude, as evoked with a common BI paradigm.

Subdissociative intranasal ketamine plus standard pain therapy versus standard pain therapy in the treatment of paediatric sickle cell disease vaso-occlusive crises in resource-limited settings: study protocol for a randomised controlled trial

PubMed Central

Sawe, Hendry Robert; Mfinanga, Juma A; Nshom, Ernest; Helm, Ethan; Moore, Charity G; Runyon, Michael S; Reynolds, Stacy L

2017-01-01

Introduction Pediatric sickle cell disease, highly prevalent in sub-Saharan Africa, carries great morbidity and mortality risk. Limited resources and monitoring make management of acute vaso-occlusive crises challenging. This study aims to evaluate the efficacy and safety of subdissociative intranasal ketamine as a cheap, readily available and easily administered adjunct to standard pain therapy. We hypothesise that subdissociative, intranasal ketamine may significantly augment current approaches to pain management in resource-limited settings in a safe and cost-effective manner. Methods and analysis This is a multicentred, randomised, double-blind, placebo-controlled trial enrolling children 4–16 years of age with sickle cell disease and painful vaso-occlusive pain crises. Study sites include two sub-Saharan teaching and referral hospitals with acute intake areas. All patients receive standard analgesic therapy during evaluation. Patients randomised to the treatment arm receive 1 mg/kg intranasal ketamine at onset of therapy, while placebo arm participants receive volume-matched intranasal normal saline. All participants and clinical staff are blinded to the treatment allocation. Data will be analysed on an intention-to-treat basis. Primary endpoints are changes in self-report pain scales (Faces Pain Scale-Revised) at 30, 60 and 120 minutes and rates of adverse events. Secondary endpoints include hospital length of stay, total analgesia use and quality of life assessment 2–3 weeks postintervention. Ethics and dissemination The research methods for this study have been approved by the Cameroon Baptist Convention Health Board Institutional Review Board (IRB2015-07), the Tanzanian National Institute for Medical Research (NIMR/HQ/R.8a/Vol. IX/2299), Muhimbili National Hospital IRB (MNH/IRB/I/2015/14) and the Tanzanian Food and Drugs Authority (TFDA0015/CTR/0015/9). Data reports will be provided to the Data and Safety Monitoring Board (DSMB) periodically throughout the study as well as all reports of adverse events. All protocol amendments will also be reviewed by the DSMB. Study results, regardless of direction or amplitude, will be submitted for publication in relevant peer-reviewed journals. Trial registration ClinicalTrials.Gov, NCT02573714. Date of registration: 8 October 2015. Pre-results. PMID:28698351

Aiming to Improve Readmissions Through InteGrated Hospital Transitions (AIRTIGHT): study protocol for a randomized controlled trial.

PubMed

McWilliams, Andrew; Roberge, Jason; Moore, Charity G; Ashby, Avery; Rossman, Whitney; Murphy, Stephanie; McCall, Stephannie; Brown, Ryan; Carpenter, Shannon; Rissmiller, Scott; Furney, Scott

2016-12-19

Hospital readmissions remain highly prevalent despite being the target of policies and financial penalties. Evidence comparing the effectiveness and costs of interventions to reduce readmissions is lacking, leaving healthcare systems with little guidance on how to improve quality and avoid costly penalties. Effective interventions likely need to bridge inpatient and outpatient settings, incorporate information technology, and use dedicated providers. Such complex innovations will require rigorous evaluation. The framework of quality improvement research provides an approach that both improves care locally and contributes to closing the current knowledge gaps for readmissions. In this trial, we will study a comprehensive intervention that incorporates these recommendations into an integrated practice unit, called transition services, with an aim of reducing 30-day readmission rates. We describe a nonblinded, pragmatic, controlled trial with two parallel groups comprising an evaluation of the effect of referral to a provider-led integrated practice unit, inclusive of comprehensive multidisciplinary care, dedicated paramedicine providers, and virtual visits, on 30-day readmission rates for high-risk hospitalized patients. An automated risk-scoring system will randomly generate referrals to either transition services or usual care for 1520 hospitalized patients who score as high-risk for readmission. Transition services will then engage with patients in the hospital setting using a patient navigator and provide bridging outpatient services for the 30 days following discharge. All outcome data are retrieved electronically from administrative medical records. After reapplication of inclusion and exclusion criteria at the time of hospital discharge, analyses will follow the intention-to-treat principle such that patients will be analyzed on the basis of the referral group to which they were initially randomized. The hospital transition program under study is complex and integrates the latest recommendations for readmission reduction strategies. As healthcare systems innovate to address readmissions through such complex interventions, there is significant benefit for stakeholders to have a clear understanding of the potential reach, cost, and real-world effectiveness. The pragmatic methods described here provide a template for conducting quality improvement research that fits seamlessly into existing care delivery and improvement efforts, leading to better-informed strategic decisions and the investments necessary to transform care and value for patients. ClinicalTrials.gov, NCT02763202 . Registered 3 March 2016 (retrospectively registered).

Action to Support Practices Implement Research Evidence (ASPIRE): protocol for a cluster-randomised evaluation of adaptable implementation packages targeting 'high impact' clinical practice recommendations in general practice.

PubMed

Willis, Thomas A; Hartley, Suzanne; Glidewell, Liz; Farrin, Amanda J; Lawton, Rebecca; McEachan, Rosemary R C; Ingleson, Emma; Heudtlass, Peter; Collinson, Michelle; Clamp, Susan; Hunter, Cheryl; Ward, Vicky; Hulme, Claire; Meads, David; Bregantini, Daniele; Carder, Paul; Foy, Robbie

2016-02-29

There are recognised gaps between evidence and practice in general practice, a setting which provides particular challenges for implementation. We earlier screened clinical guideline recommendations to derive a set of 'high impact' indicators based upon criteria including potential for significant patient benefit, scope for improved practice and amenability to measurement using routinely collected data. We aim to evaluate the effectiveness and cost-effectiveness of a multifaceted, adaptable intervention package to implement four targeted, high impact recommendations in general practice. The research programme Action to Support Practice Implement Research Evidence (ASPIRE) includes a pair of pragmatic cluster-randomised trials which use a balanced incomplete block design. Clusters are general practices in West Yorkshire, United Kingdom (UK), recruited using an 'opt-out' recruitment process. The intervention package adapted to each recommendation includes combinations of audit and feedback, educational outreach visits and computerised prompts with embedded behaviour change techniques selected on the basis of identified needs and barriers to change. In trial 1, practices are randomised to adapted interventions targeting either diabetes control or risky prescribing and those in trial 2 to adapted interventions targeting either blood pressure control in patients at risk of cardiovascular events or anticoagulation in atrial fibrillation. The respective primary endpoints comprise achievement of all recommended target levels of haemoglobin A1c (HbA1c), blood pressure and cholesterol in patients with type 2 diabetes, a composite indicator of risky prescribing, achievement of recommended blood pressure targets for specific patient groups and anticoagulation prescribing in patients with atrial fibrillation. We are also randomising practices to a fifth, non-intervention control group to further assess Hawthorne effects. Outcomes will be assessed using routinely collected data extracted 1 year after randomisation. Economic modelling will estimate intervention cost-effectiveness. A process evaluation involving eight non-trial practices will examine intervention delivery, mechanisms of action and unintended consequences. ASPIRE will provide 'real-world' evidence about the effects, cost-effectiveness and delivery of adapted intervention packages targeting high impact recommendations. By implementing our adaptable intervention package across four distinct clinical topics, and using 'opt-out' recruitment, our findings will provide evidence of wider generalisability. ISRCTN91989345.

Utilization of a Clinical Trial Management System for the Whole Clinical Trial Process as an Integrated Database: System Development

PubMed Central

Park, Yu Rang; Yoon, Young Jo; Koo, HaYeong; Yoo, Soyoung; Choi, Chang-Min; Beck, Sung-Ho

2018-01-01

Background Clinical trials pose potential risks in both communications and management due to the various stakeholders involved when performing clinical trials. The academic medical center has a responsibility and obligation to conduct and manage clinical trials while maintaining a sufficiently high level of quality, therefore it is necessary to build an information technology system to support standardized clinical trial processes and comply with relevant regulations. Objective The objective of the study was to address the challenges identified while performing clinical trials at an academic medical center, Asan Medical Center (AMC) in Korea, by developing and utilizing a clinical trial management system (CTMS) that complies with standardized processes from multiple departments or units, controlled vocabularies, security, and privacy regulations. Methods This study describes the methods, considerations, and recommendations for the development and utilization of the CTMS as a consolidated research database in an academic medical center. A task force was formed to define and standardize the clinical trial performance process at the site level. On the basis of the agreed standardized process, the CTMS was designed and developed as an all-in-one system complying with privacy and security regulations. Results In this study, the processes and standard mapped vocabularies of a clinical trial were established at the academic medical center. On the basis of these processes and vocabularies, a CTMS was built which interfaces with the existing trial systems such as the electronic institutional review board health information system, enterprise resource planning, and the barcode system. To protect patient data, the CTMS implements data governance and access rules, and excludes 21 personal health identifiers according to the Health Insurance Portability and Accountability Act (HIPAA) privacy rule and Korean privacy laws. Since December 2014, the CTMS has been successfully implemented and used by 881 internal and external users for managing 11,645 studies and 146,943 subjects. Conclusions The CTMS was introduced in the Asan Medical Center to manage the large amounts of data involved with clinical trial operations. Inter- and intraunit control of data and resources can be easily conducted through the CTMS system. To our knowledge, this is the first CTMS developed in-house at an academic medical center side which can enhance the efficiency of clinical trial management in compliance with privacy and security laws. PMID:29691212

Limitations of basing screening policies on screening trials: The US Preventive Services Task Force and Prostate Cancer Screening.

PubMed

Etzioni, Ruth; Gulati, Roman; Cooperberg, Matt R; Penson, David M; Weiss, Noel S; Thompson, Ian M

2013-04-01

The US Preventive Services Task Force recently recommended against prostate-specific antigen screening for prostate cancer based primarily on evidence from the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. : To examine limitations of basing screening policy on evidence from screening trials. We reviewed published modeling studies that examined population and trial data. The studies (1) project the roles of screening and changes in primary treatment in the US mortality decline; (2) extrapolate the ERSPC mortality reduction to the long-term US setting; (3) estimate overdiagnosis based on US incidence trends; and (4) quantify the impact of control arm screening on PLCO mortality results. Screening plausibly explains 45% and changes in primary treatment can explain 33% of the US prostate cancer mortality decline. Extrapolating the ERSPC results to the long-term US setting implies an absolute mortality reduction at least 5 times greater than that observed in the trial. Approximately 28% of screen-detected cases are overdiagnosed in the United States versus 58% of screen-detected cases suggested by the ERSPC results. Control arm screening can explain the null result in the PLCO trial. Modeling studies indicate that population trends and trial results extended to the long-term population setting are consistent with greater benefit of prostate-specific antigen screening-and more favorable harm-benefit tradeoffs-than has been suggested by empirical trial evidence.

Can Alzheimer disease be prevented by amyloid-β immunotherapy?

PubMed Central

Lemere, Cynthia A.; Masliah, Eliezer

2010-01-01

Alzheimer disease (AD) is the most common form of dementia. The amyloid-β (Aβ) peptide has become a major therapeutic target in AD on the basis of pathological, biochemical and genetic evidence that supports a role for this molecule in the disease process. Active and passive Aβ immunotherapies have been shown to lower cerebral Aβ levels and improve cognition in animal models of AD. In humans, dosing in the phase II clinical trial of the AN1792 Aβ vaccine was stopped when ~6% of the immunized patients developed meningoencephalitis. However, some plaque clearance and modest clinical improvements were observed in patients following immunization. As a result of this study, at least seven passive Aβ immunotherapies are now in clinical trials in patients with mild to moderate AD. Several second-generation active Aβ vaccines are also in early clinical trials. On the basis of preclinical studies and the limited data from clinical trials, Aβ immunotherapy might be most effective in preventing or slowing the progression of AD when patients are immunized before or in the very earliest stages of disease onset. Biomarkers for AD and imaging technology have improved greatly over the past 10 years and, in the future, might be used to identify presymptomatic, at-risk individuals who might benefit from Aβ immunization. PMID:20140000

Exploring threats to generalisability in a large international rehabilitation trial (AVERT)

PubMed Central

Bernhardt, Julie; Raffelt, Audrey; Churilov, Leonid; Lindley, Richard I; Speare, Sally; Ancliffe, Jacqueline; Katijjahbe, Md Ali; Hameed, Shahul; Lennon, Sheila; McRae, Anna; Tan, Dawn; Quiney, Jan; Williamson, Hannah C; Collier, Janice; Dewey, Helen M; Donnan, Geoffrey A; Langhorne, Peter; Thrift, Amanda G

2015-01-01

Objective The purpose of this paper is to examine potential threats to generalisability of the results of a multicentre randomised controlled trial using data from A Very Early Rehabilitation Trial (AVERT). Design AVERT is a prospective, parallel group, assessor-blinded randomised clinical trial. This paper presents data assessing the generalisability of AVERT. Setting Acute stroke units at 44 hospitals in 8 countries. Participants The first 20 000 patients screened for AVERT, of whom 1158 were recruited and randomised. Model We use the Proximal Similarity Model, which considers the person, place, and setting and practice, as a framework for considering generalisability. As well as comparing the recruited patients with the target population, we also performed an exploratory analysis of the demographic, clinical, site and process factors associated with recruitment. Results The demographics and stroke characteristics of the included patients in the trial were broadly similar to population-based norms, with the exception that AVERT had a greater proportion of men. The most common reason for non-recruitment was late arrival to hospital (ie, >24 h). Overall, being older and female reduced the odds of recruitment to the trial. More women than men were excluded for most of the reasons, including refusal. The odds of exclusion due to early deterioration were particularly high for those with severe stroke (OR=10.4, p<0.001, 95% CI 9.27 to 11.65). Conclusions A model which explores person, place, and setting and practice factors can provide important information about the external validity of a trial, and could be applied to other clinical trials. Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN12606000185561) and Clinicaltrials.gov (NCT01846247). PMID:26283667

Massed Trials versus Trials Embedded into Game Play: Child Outcomes and Preference

ERIC Educational Resources Information Center

Ledford, Jennifer R.; Chazin, Kate T.; Harbin, Emilee R.; Ward, Sarah E.

2017-01-01

Limited data are available regarding how response prompting procedures should be used in early childhood settings. The purpose of this study was to compare the efficiency of progressive time delay instruction presented via two trial arrangements: massed and embedded. During massed trial sessions, a short instructional session was conducted,…

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.

Should academic medical centers conduct clinical trials of the efficacy of intercessory prayer?

PubMed

Halperin, E C

2001-08-01

Intercessory prayers for health or healing are requests to an object of worship for the preservation or restoration of health. There has been a recent proliferation of clinical trials that compare the health outcome of a group of prayed-for patients with that of controls, to test the efficacy of intercessory prayer. In this essay, the author defines the concept of intercessory prayer, contrasts it with other forms of prayer, and reviews the literature concerning clinical trials of its efficacy. The arguments put forward in favor of conducting such trials and those against are described and the reader is invited to consider their relative merits. The author concludes by discussing the potential power of faith in healing, reviewing the philosophical basis and pitfalls of clinical trials of intercessory prayer, and urging readers to weigh the arguments for and against such trials in academic medicine.

Assessing fitness to stand trial: the utility of the Fitness Interview Test (revised edition).

PubMed

Zapf, P A; Roesch, R; Viljoen, J L

2001-06-01

In Canada most evaluations of fitness to stand trial are conducted on an inpatient basis. This costs time and money, and deprives those defendants remanded for evaluation of liberty. This research assessed the predictive efficiency of the Fitness Interview Test, revised edition (FIT) as a screening instrument for fitness to stand trial. We compared decisions about fitness to stand trial, based on the FIT, with the results of institution-based evaluations for 2 samples of men remanded for inpatient fitness assessments. The FIT demonstrates excellent utility as a screening instrument. The FIT shows good sensitivity and negative predictive power, which suggests that it can reliably screen those individuals who are clearly fit to stand trial, before they are remanded to an inpatient facility for a fitness assessment. We discuss the implications for evaluating fitness to stand trial, particularly in terms of the need for community-based alternatives to traditional forensic assessments.

Inside information: Financial conflicts of interest for research subjects in early phase clinical trials.

PubMed

Helft, Paul R; Ratain, Mark J; Epstein, Richard A; Siegler, Mark

2004-05-05

In recent years, several research subjects have told us that they had bought or intended to buy stock in the companies sponsoring the clinical trials in which they were enrolled. This situation has led us to ask what, if any, are physician-investigators' scientific, ethical, and legal responsibilities concerning research subjects who choose to buy stock in the companies sponsoring the clinical trials in which they are participating. Although the scope of this problem is unknown and is likely to be small, this commentary examines the scientific, ethical, and legal concerns raised by such activities on the part of research subjects enrolled in early phase clinical trials. In addition, this commentary also outlines the basis for our opinion that research subjects involved in an early phase clinical trial should avoid the financial conflicts of interest created by trading stock in the company sponsoring the clinical trial.

The proposed EU-regulation on clinical trials on medicinal products: an unethical proposal?

PubMed

Heringa, Jilles; Dute, Joseph

2013-09-01

The Commission has proposed a regulation 'on clinical trials on medicinal products for human use' to introduce one regulatory framework for clinical trials in the European Union. This regulation should replace the current clinical trials directive (2001/20/EC). In this article we describe and critically review the main provisions of the proposed regulation. We assess the consequences for a sound authorisation procedure of clinical trials and the level of protection for human subjects. We note that the proposed regulation is inconsistent with applicable international legal documents, such as the Biomedicine Convention and the Declaration of Helsinki. We conclude that the proposed regulation does not ensure a "high level of human health protection"--required by its legal basis in the TFEU--because it may force Member States concerned to accept a reporting Member States' approval of--in their estimation--an unethical clinical trial.

Standardising the reporting of outcomes in gastric cancer surgery trials: protocol for the development of a core outcome set and accompanying outcome measurement instrument set (the GASTROS study).

PubMed

Alkhaffaf, Bilal; Glenny, Anne-Marie; Blazeby, Jane M; Williamson, Paula; Bruce, Iain A

2017-08-09

Gastric cancer is one of the leading causes of cancer-related deaths worldwide. Whilst surgery is the mainstay of curative treatment, it is associated with significant risks. Surgical strategies for treating gastric cancer should be based on evidence from systematic reviews of well-designed randomised controlled trials. However, inconsistencies in the reporting of outcomes from these trials makes evidence synthesis unreliable. We present a protocol for an international consensus study to develop a standardised set of outcomes and measurement tools - a 'core outcome set' (COS) - to be used by all future trials examining therapeutic surgical interventions for gastric cancer. The GASTROS study aims to standardise the reporting of outcomes in gastric cancer surgery trials through an international consensus process of key stakeholders including health care professionals and patients. The first of three stages in the study will identify a 'long-list' of potentially important outcomes to be prioritised. These will be extracted from a systematic review of relevant academic literature and patient interviews. Stage 2 will comprise an eDelphi survey which will consider the views of patients, nurse specialists and surgeons to prioritise the most important outcomes. A meeting of stakeholder representatives will ratify the COS. Stage 3 will focus on identifying appropriate instruments to measure the prioritised outcomes by means of quality assessment of available measurement instruments and stakeholder consultation. This study aims to standardise the reporting of outcomes in future trials examining therapeutic surgical interventions for gastric cancer. It is anticipated that standardisation of outcome reporting in these surgical effectiveness trials will enhance the evidence base for clinical practice. Highlighting outcomes of greatest importance to patients will ensure that their perspectives are central to research in this field.

Novel throughput phenotyping platforms in plant genetic studies.

PubMed

Montes, Juan M; Melchinger, Albrecht E; Reif, Jochen C

2007-10-01

Unraveling the genetic basis of complex traits in plants is limited by the lack of appropriate phenotyping platforms that enable high-throughput screening of many genotypes in multilocation field trials. Near-infrared spectroscopy on agricultural harvesters and spectral reflectance of plant canopies have recently been reported as promising components of novel phenotyping platforms. Understanding the genetic basis of complex traits is now within reach with the use of these new techniques.

Development of a core outcome set for clinical trials in squamous cell carcinoma: study protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey.

PubMed

Schlessinger, Daniel I; Iyengar, Sanjana; Yanes, Arianna F; Chiren, Sarah G; Godinez-Puig, Victoria; Chen, Brian R; Kurta, Anastasia O; Schmitt, Jochen; Deckert, Stefanie; Furlan, Karina C; Poon, Emily; Cartee, Todd V; Maher, Ian A; Alam, Murad; Sobanko, Joseph F

2017-07-12

Squamous cell carcinoma (SCC) is a common skin cancer that poses a risk of metastasis. Clinical investigations into SCC treatment are common, but the outcomes reported are highly variable, omitted, or clinically irrelevant. The outcome heterogeneity and reporting bias of these studies leave clinicians unable to accurately compare studies. Core outcome sets (COSs) are an agreed minimum set of outcomes recommended to be measured and reported in all clinical trials of a given condition or disease. Although COSs are under development for several dermatologic conditions, work has yet to be done to identify core outcomes specific for SCC. Outcome extraction for COS generation will occur via four methods: (1) systematic literature review; (2) patient interviews; (3) other published sources; and (4) input from stakeholders in medicine, pharmacy, and other relevant industries. The list of outcomes will be revaluated by the Measuring PRiority Outcome Variables via Excellence in Dermatologic surgery (IMPROVED) Steering Committee. Delphi processes will be performed separately by expert clinicians and patients to condense the list of outcomes generated. A consensus meeting with relevant stakeholders will be conducted after the Delphi exercise to further select outcomes, taking into account participant scores. At the end of the meeting, members will vote and decide on a final recommended set of core outcomes. The Core Outcome Measures in Effectiveness Trials (COMET) organization and the Cochrane Skin Group - Core Outcome Set Initiative (CSG-COUSIN) will serve as advisers throughout the COS generation process. Comparison of clinical trials via systematic reviews and meta-analyses is facilitated when investigators study outcomes that are relevant and similar. The aim of this project is to develop a COS to guide use for future clinical trials.

Randomized Controlled Trial in Clinical Settings to Evaluate Effectiveness of Coping Skills Education Used with Progressive Tinnitus Management

ERIC Educational Resources Information Center

Henry, James A.; Thielman, Emily J.; Zaugg, Tara L.; Kaelin, Christine; Schmidt, Caroline J.; Griest, Susan; McMillan, Garnett P.; Myers, Paula; Rivera, Izel; Baldwin, Robert; Carlson, Kathleen

2017-01-01

Purpose: This randomized controlled trial evaluated, within clinical settings, the effectiveness of coping skills education that is provided with progressive tinnitus management (PTM). Method: At 2 Veterans Affairs medical centers, N = 300 veterans were randomized to either PTM intervention or 6-month wait-list control. The PTM intervention…

Automatic activation of word phonology from print in deep dyslexia.

PubMed

Katz, R B; Lanzoni, S M

1992-11-01

The performance of deep dyslexics in oral reading and other tasks suggests that they are poor at activating the phonology of words and non-words from printed stimuli. As the tasks ordinarily used to test deep dyslexics require controlled processing, it is possible that the phonology of printed words can be better activated on an automatic basis. This study investigated this possibility by testing a deep dyslexic patient on a lexical decision task with pairs of stimuli presented simultaneously. In Experiment 1, which used content words as stimuli, the deep dyslexic, like normal subjects, showed faster reaction times on trials with rhyming, similarly spelled stimuli (e.g. bribe-tribe) than on control trials (consisting of non-rhyming, dissimilarly spelled words), but slower reaction times on trials with non-rhyming, similarly spelled stimuli (e.g. couch-touch). When the experiment was repeated using function words as stimuli, the patient no longer showed a phonological effect. Therefore, the phonological activation of printed content words by deep dyslexics may be better than would be expected on the basis of their oral reading performance.

Asymptotic behavior and interpretation of virtual states: The effects of confinement and of basis sets

NASA Astrophysics Data System (ADS)

Boffi, Nicholas M.; Jain, Manish; Natan, Amir

2016-02-01

A real-space high order finite difference method is used to analyze the effect of spherical domain size on the Hartree-Fock (and density functional theory) virtual eigenstates. We show the domain size dependence of both positive and negative virtual eigenvalues of the Hartree-Fock equations for small molecules. We demonstrate that positive states behave like a particle in spherical well and show how they approach zero. For the negative eigenstates, we show that large domains are needed to get the correct eigenvalues. We compare our results to those of Gaussian basis sets and draw some conclusions for real-space, basis-sets, and plane-waves calculations.

Exact solution for the hydrogen atom confined by a dielectric continuum and the correct basis set to study many-electron atoms under similar confinements

NASA Astrophysics Data System (ADS)

Martínez-Sánchez, Michael-Adán; Aquino, Norberto; Vargas, Rubicelia; Garza, Jorge

2017-12-01

The Schrödinger equation associated to the hydrogen atom confined by a dielectric continuum is solved exactly and suggests the appropriate basis set to be used when an atom is immersed in a dielectric continuum. Exact results show that this kind of confinement spread the electron density, which is confirmed through the Shannon entropy. The basis set suggested by the exact results is similar to Slater type orbitals and it was applied on two-electron atoms, where the H- ion ejects one electron for moderate confinements for distances much larger than those commonly used to generate cavities in solvent models.

Third party laboratory data management: Perspective with respect to clinical data management.

PubMed

Johnson, Jasmin; Kanagali, Vishwanath; Prabu, D

2014-01-01

Third party lab vendor provides support for laboratory, biological samples analytics data, collected during the clinical trial. Third party laboratory data is considered to be very significant for the clinical trial data management process. Although outsourcing these services is considered to be advantageous for clinical trials, there are some risks involved. Hence, pharmaceutical companies proactively select, track and evaluate third party vendors on a regular basis before, during and after the completion of the contract. The data manager has a significant role to play in effective management of third party vendor data.

Sample size calculations for comparative clinical trials with over-dispersed Poisson process data.

PubMed

Matsui, Shigeyuki

2005-05-15

This paper develops a new formula for sample size calculations for comparative clinical trials with Poisson or over-dispersed Poisson process data. The criteria for sample size calculations is developed on the basis of asymptotic approximations for a two-sample non-parametric test to compare the empirical event rate function between treatment groups. This formula can accommodate time heterogeneity, inter-patient heterogeneity in event rate, and also, time-varying treatment effects. An application of the formula to a trial for chronic granulomatous disease is provided. Copyright 2004 John Wiley & Sons, Ltd.

Third party laboratory data management: Perspective with respect to clinical data management

PubMed Central

Johnson, Jasmin; Kanagali, Vishwanath; Prabu, D.

2014-01-01

Third party lab vendor provides support for laboratory, biological samples analytics data, collected during the clinical trial. Third party laboratory data is considered to be very significant for the clinical trial data management process. Although outsourcing these services is considered to be advantageous for clinical trials, there are some risks involved. Hence, pharmaceutical companies proactively select, track and evaluate third party vendors on a regular basis before, during and after the completion of the contract. The data manager has a significant role to play in effective management of third party vendor data. PMID:24551587

Contemporary Australian outcomes in childhood and adolescent type 1 diabetes: 10 years post the Diabetes Control and Complications Trial.

PubMed

Ambler, Geoffrey R; Fairchild, Jan; Craig, Maria E; Cameron, Fergus J

2006-01-01

The reporting of the results of the Diabetes Control and Complications Trial in 1993 has led to a major reappraisal of management practices and outcomes in type 1 diabetes in children and adolescents. A considerable body of outcome data has been generated from Australia in this post-Diabetes Control and Complications Trial era relating to incidence, metabolic control, growth, hypoglycaemia, microvascular and macrovascular complications, cognition, behaviour and quality of life. These data are important in planning future management strategies and resource allocation and as a basis for future research.

The US Food and Drug Administration's expedited approval programs: Evidentiary standards, regulatory trade-offs, and potential improvements.

PubMed

Wallach, Joshua D; Ross, Joseph S; Naci, Huseyin

2018-06-01

The US Food and Drug Administration has several regulatory programs and pathways to expedite the development and approval of therapeutic agents aimed at treating serious or life-debilitating conditions. A common feature of these programs is the regulatory flexibility, which allows for a customized approval approach that enables market authorization on the basis of less rigorous evidence, in exchange for requiring postmarket evidence generation. An increasing share of therapeutic agents approved by the Food and Drug Administration in recent years are associated with expedited programs. In this article, we provide an overview of the evidentiary standards required by the Food and Drug Administration's expedited development and review programs, summarize the findings of the recent academic literature demonstrating some of the limitations of these programs, and outline potential opportunities to address these limitations. Recent evidence suggests that therapeutic agents in the Food and Drug Administration's expedited programs are approved on the basis of fewer and smaller studies that may lack comparator groups and random allocation, and rather than focusing on clinical outcomes for study endpoints, rely instead on surrogate markers of disease. Once on the market, agents receiving expedited approvals are often quickly incorporated into clinical practice, and evidence generated in the postmarket period may not necessarily address the evidentiary limitations at the time of market entry. Furthermore, not all pathways require additional postmarket studies. Evidence suggests that drugs in expedited approval programs are associated with a greater likelihood that the Food and Drug Administration will take a safety action following market entry. There are several opportunities to improve the timeliness, information value, and validity of the pre- and postmarket studies of therapeutic agents receiving expedited approvals. When use of nonrandomized and uncontrolled studies cannot be avoided prior to market entry, randomized trials should be mandatory in the postmarket period, unless there are strong justifications for not carrying out such studies. In the premarket period, validity of the surrogate markers can be improved by more rigorously evaluating their correlation with patient-relevant clinical outcomes. Opportunities to reduce the duration, complexity, and cost of postmarket randomized trials should not compromise their validity and instead incorporate pragmatic "real-world" design elements. Despite recent enthusiasm for widely using real-world evidence, adaptive designs, and pragmatic trials in the regulatory setting, caution is warranted until large-scale empirical evaluations demonstrate their validity compared to more traditional trial designs.

Quality and quantity of information in summary basis of decision documents issued by health Canada.

PubMed

Habibi, Roojin; Lexchin, Joel

2014-01-01

Health Canada's Summary Basis of Decision (SBD) documents outline the clinical trial information that was considered in approving a new drug. We examined the ability of SBDs to inform clinician decision-making. We asked if SBDs answered three questions that clinicians might have prior to prescribing a new drug: 1) Do the characteristics of patients enrolled in trials match those of patients in their practice? 2) What are the details concerning the drug's risks and benefits? 3) What are the basic characteristics of trials? 14 items of clinical trial information were identified from all SBDs published on or before April 2012. Each item received a score of 2 (present), 1 (unclear) or 0 (absent). The unit of analysis was the individual SBD, and an overall SBD score was derived based on the sum of points for each item. Scores were expressed as a percentage of the maximum possible points, and then classified into five descriptive categories based on that score. Additionally, three overall 'component' scores were tallied for each SBD: "patient characteristics", "benefit/risk information" and "basic trial characteristics". 161 documents, spanning 456 trials, were analyzed. The majority (126/161) were rated as having information sometimes present (score of >33 to 66%). No SBDs had either no information on any item, or 100% of the information. Items in the patient characteristics component scored poorest (mean component score of 40.4%), while items corresponding to basic trial information were most frequently provided (mean component score of 71%). The significant omissions in the level of clinical trial information in SBDs provide little to aid clinicians in their decision-making. Clinicians' preferred source of information is scientific knowledge, but in Canada, access to such information is limited. Consequently, we believe that clinicians are being denied crucial tools for decision-making.

The Stochastic Early Reaction, Inhibition, and late Action (SERIA) model for antisaccades

PubMed Central

2017-01-01

The antisaccade task is a classic paradigm used to study the voluntary control of eye movements. It requires participants to suppress a reactive eye movement to a visual target and to concurrently initiate a saccade in the opposite direction. Although several models have been proposed to explain error rates and reaction times in this task, no formal model comparison has yet been performed. Here, we describe a Bayesian modeling approach to the antisaccade task that allows us to formally compare different models on the basis of their evidence. First, we provide a formal likelihood function of actions (pro- and antisaccades) and reaction times based on previously published models. Second, we introduce the Stochastic Early Reaction, Inhibition, and late Action model (SERIA), a novel model postulating two different mechanisms that interact in the antisaccade task: an early GO/NO-GO race decision process and a late GO/GO decision process. Third, we apply these models to a data set from an experiment with three mixed blocks of pro- and antisaccade trials. Bayesian model comparison demonstrates that the SERIA model explains the data better than competing models that do not incorporate a late decision process. Moreover, we show that the early decision process postulated by the SERIA model is, to a large extent, insensitive to the cue presented in a single trial. Finally, we use parameter estimates to demonstrate that changes in reaction time and error rate due to the probability of a trial type (pro- or antisaccade) are best explained by faster or slower inhibition and the probability of generating late voluntary prosaccades. PMID:28767650

Randomized, double-blind, placebo-controlled trial of oral docusate in the management of constipation in hospice patients.

PubMed

Tarumi, Yoko; Wilson, Mitchell P; Szafran, Olga; Spooner, G Richard

2013-01-01

The stool softener docusate is widely used in the management of constipation in hospice patients. There is little experimental evidence to support this practice, and no randomized trials have been conducted in the hospice setting. To assess the efficacy of docusate in hospice patients. This was a 10-day, prospective, randomized, double-blind, placebo-controlled trial of docusate and sennosides vs. placebo and sennosides in hospice patients in Edmonton, Alberta. Patients were included if they were age 18 years or older, able to take oral medications, did not have a gastrointestinal stoma, and had a Palliative Performance Scale score of 20% or more. The primary outcome measures were stool frequency, volume, and consistency. Secondary outcomes were patient perceptions of bowel movements (difficulty and completeness of evacuation) and bowel-related interventions. A total of 74 patients were randomized into the study (35 to the docusate group and 39 to the placebo group). There were neither significant differences between the groups in stool frequency, volume, or consistency, nor in difficulty or completeness of evacuation. On the Bristol Stool Form Scale, more patients in the placebo group had Type 4 (smooth and soft) and Type 5 (soft blobs) stool, whereas in the docusate group, more had Type 3 (sausage like) and Type 6 (mushy) stool (P=0.01). There was no significant benefit of docusate plus sennosides compared with placebo plus sennosides in managing constipation in hospice patients. Docusate use should be considered on an individual basis. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

The business case for provider participation in clinical trials research: an application to the National Cancer Institute's community clinical oncology program.

PubMed

Song, Paula H; Reiter, Kristin L; Weiner, Bryan J; Minasian, Lori; McAlearney, Ann Scheck

2013-01-01

Provider-based research networks (PBRNs) make clinical trials available in community-based practice settings, where most people receive their care, but provider participation requires both financial and in-kind contributions. The aim of this study was to explore whether providers believe there is a business case for participating in PBRNs and what factors contribute to the business case. We use a multiple case study methodology approach to examine the National Cancer Institute's community clinical oncology program, a long-standing federally funded PBRN. Interviews with 41 key informants across five sites, selected on the basis of organizational maturity, were conducted using a semistructured interview guide. We analyzed interview transcripts using an iterative, deductive process to identify themes and subthemes in the data. We found that a business case for provider participation in PBRNs may exist if both direct and indirect financial benefits are identified and included in the analysis and if the time horizon is long enough to allow those benefits to be realized. We identified specific direct and indirect financial benefits that were perceived as important contributors to the business case and the perceived length of time required for a positive return to accrue. As the lack of a business case may result in provider reluctance to participate in PBRNs, knowledge of the benefits we identified may be crucial to encouraging and sustaining participation, thereby preserving patient access to innovative community-based treatments. The results are also relevant to federally funded PBRNs outside of oncology or to providers considering participation in any clinical trials research.

Effectiveness of an intensive E-mail based intervention in smoking cessation (TABATIC study): study protocol for a randomized controlled trial.

PubMed

Díaz-Gete, Laura; Puigdomènech, Elisa; Briones, Elena Mercedes; Fàbregas-Escurriola, Mireia; Fernandez, Soraya; Del Val, Jose Luis; Ballvé, Jose Luis; Casajuana, Marc; Sánchez-Fondevila, Jessica; Clemente, Lourdes; Castaño, Carmen; Martín-Cantera, Carlos

2013-04-18

Intensive interventions on smoking cessation increase abstinence rates. However, few electronic mail (E-mail) based intensive interventions have been tested in smokers and none in primary care (PC) setting. The aim of the present study is to evaluate the effectiveness of an intensive E-mail based intervention in smokers attending PC services. Randomized Controlled Multicentric Trial. 1060 smokers aged between 18-70 years from Catalonia, Salamanca and Aragón (Spain) who have and check regularly an E-mail account. Patients will be randomly assigned to control or intervention group. Six phase intensive intervention with two face to face interviews and four automatically created and personal E-mail patients tracking, if needed other E-mail contacts will be made. Control group will receive a brief advice on smoking cessation. Will be measured at 6 and 12 months after intervention: self reported continuous abstinence (confirmed by cooximetry), point prevalence abstinence, tobacco consumption, evolution of stage according to Prochaska and DiClemente's Stages of Change Model, length of visit, costs for the patient to access Primary Care Center. Descriptive and logistic and Poisson regression analysis under the intention to treat basis using SPSS v.17. The proposed intervention is an E-mail based intensive intervention in smokers attending primary care. Positive results could be useful to demonstrate a higher percentage of short and long-term abstinence among smokers attended in PC in Spain who regularly use E-mail. Furthermore, this intervention could be helpful in all health services to help smokers to quit. Clinical Trials.gov Identifier: NCT01494246.

High-performance intraoperative cone-beam CT on a mobile C-arm: an integrated system for guidance of head and neck surgery

NASA Astrophysics Data System (ADS)

Siewerdsen, J. H.; Daly, M. J.; Chan, H.; Nithiananthan, S.; Hamming, N.; Brock, K. K.; Irish, J. C.

2009-02-01

A system for intraoperative cone-beam CT (CBCT) surgical guidance is under development and translation to trials in head and neck surgery. The system provides 3D image updates on demand with sub-millimeter spatial resolution and soft-tissue visibility at low radiation dose, thus overcoming conventional limitations associated with preoperative imaging alone. A prototype mobile C-arm provides the imaging platform, which has been integrated with several novel subsystems for streamlined implementation in the OR, including: real-time tracking of surgical instruments and endoscopy (with automatic registration of image and world reference frames); fast 3D deformable image registration (a newly developed multi-scale Demons algorithm); 3D planning and definition of target and normal structures; and registration / visualization of intraoperative CBCT with the surgical plan, preoperative images, and endoscopic video. Quantitative evaluation of surgical performance demonstrates a significant advantage in achieving complete tumor excision in challenging sinus and skull base ablation tasks. The ability to visualize the surgical plan in the context of intraoperative image data delineating residual tumor and neighboring critical structures presents a significant advantage to surgical performance and evaluation of the surgical product. The system has been translated to a prospective trial involving 12 patients undergoing head and neck surgery - the first implementation of the research prototype in the clinical setting. The trial demonstrates the value of high-performance intraoperative 3D imaging and provides a valuable basis for human factors analysis and workflow studies that will greatly augment streamlined implementation of such systems in complex OR environments.

Early clinical observations on the use of imatinib mesylate in FOP: A report of seven cases.

PubMed

Kaplan, Frederick S; Andolina, Jeffrey R; Adamson, Peter C; Teachey, David T; Finklestein, Jerry Z; Ebb, David H; Whitehead, Benjamin; Jacobs, Benjamin; Siegel, David M; Keen, Richard; Hsiao, Edward; Pignolo, Robert J

2018-04-01

Fibrodysplasia ossificans progressiva (FOP) is an ultrarare genetic disorder of progressive, disabling heterotopic ossification (HO) for which there is presently no definitive treatment. Research studies have identified multiple potential targets for therapy in FOP, and novel drug candidates are being developed for testing in clinical trials. A complementary approach seeks to identify approved drugs that could be re-purposed for off-label use against defined targets in FOP. One such drug is imatinib mesylate, a tyrosine kinase inhibitor originally developed for use in patients with chronic myeloid leukemia (CML). Imatinib has the desirable effect of attacking multiple targets involved in the early hypoxic and inflammatory stages of FOP flare-ups, including HIF1-α, PDGFRα, c-KIT, and multiple MAP kinases. Based on compelling biologic rationale, strong preclinical data, and a favorable safety profile, imatinib has been prescribed on an off-label basis in a non-trial setting in seven children with continuous FOP flare-ups, predominantly in the axial regions, and which were not responsive to standard-of-care regimens. Anecdotal reports in these seven isolated cases document that the medication was well-tolerated with a ubiquitous reported decrease in the intensity of flare-ups in the six children who took the medication. These early clinical observations support the implementation of clinical trials in children with uncontrolled FOP flare-ups to determine if imatinib may ameliorate symptoms or alter the natural history of this debilitating and life-threatening disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Salvage therapy for locally recurrent prostate cancer after radiation.

PubMed

Marcus, David M; Canter, Daniel J; Jani, Ashesh B; Dobbs, Ryan W; Schuster, David M; Carthon, Bradley C; Rossi, Peter J

2012-12-01

External beam radiotherapy (EBRT) is widely utilized as primary therapy for clinically localized prostate cancer. For patients who develop locally recurrent disease after EBRT, local salvage therapy may be indicated. The primary modalities for local salvage treatment in this setting include radical prostatectomy, cryotherapy, and brachytherapy. To date, there is little data describing outcomes and toxicity associated with each of these salvage modalities. A review of the literature was performed to identify studies of local salvage therapy for patients who had failed primary EBRT for localized prostate cancer. We focused on prospective trials and multi-institutional retrospective series in order to identify the highest level of evidence describing these therapies. The majority of reports describing the use of local salvage treatment for recurrent prostate cancer after EBRT are single-institution, retrospective reports, although small prospective studies are available for salvage cryotherapy and salvage brachytherapy. Clinical outcomes and toxicity for each modality vary widely across studies, which is likely due to the heterogeneity of patient populations, treatment techniques, and definitions of failure. In general, most studies demonstrate that local salvage therapy after EBRT may provide long-term local control in appropriately selected patients, although toxicity is often significant. As there are no randomized trials comparing salvage treatment modalities for localized prostate cancer recurrence after EBRT, the selection of a local treatment modality should be made on a patient-by-patient basis, with careful consideration of each patient's disease characteristics and tolerance for the risks of treatment. Additional data, ideally from prospective randomized trials, is needed to guide decision making for patients with local recurrence after EBRT failure.

CCSD(T) potential energy and induced dipole surfaces for N2–H2(D2): retrieval of the collision-induced absorption integrated intensities in the regions of the fundamental and first overtone vibrational transitions.

PubMed

Buryak, Ilya; Lokshtanov, Sergei; Vigasin, Andrey

2012-09-21

The present work aims at ab initio characterization of the integrated intensity temperature variation of collision-induced absorption (CIA) in N(2)-H(2)(D(2)). Global fits of potential energy surface (PES) and induced dipole moment surface (IDS) were made on the basis of CCSD(T) (coupled cluster with single and double and perturbative triple excitations) calculations with aug-cc-pV(T,Q)Z basis sets. Basis set superposition error correction and extrapolation to complete basis set (CBS) limit techniques were applied to both energy and dipole moment. Classical second cross virial coefficient calculations accounting for the first quantum correction were employed to prove the quality of the obtained PES. The CIA temperature dependence was found in satisfactory agreement with available experimental data.

A new digitized reverse correction method for hypoid gears based on a one-dimensional probe

NASA Astrophysics Data System (ADS)

Li, Tianxing; Li, Jubo; Deng, Xiaozhong; Yang, Jianjun; Li, Genggeng; Ma, Wensuo

2017-12-01

In order to improve the tooth surface geometric accuracy and transmission quality of hypoid gears, a new digitized reverse correction method is proposed based on the measurement data from a one-dimensional probe. The minimization of tooth surface geometrical deviations is realized from the perspective of mathematical analysis and reverse engineering. Combining the analysis of complex tooth surface generation principles and the measurement mechanism of one-dimensional probes, the mathematical relationship between the theoretical designed tooth surface, the actual machined tooth surface and the deviation tooth surface is established, the mapping relation between machine-tool settings and tooth surface deviations is derived, and the essential connection between the accurate calculation of tooth surface deviations and the reverse correction method of machine-tool settings is revealed. Furthermore, a reverse correction model of machine-tool settings is built, a reverse correction strategy is planned, and the minimization of tooth surface deviations is achieved by means of the method of numerical iterative reverse solution. On this basis, a digitized reverse correction system for hypoid gears is developed by the organic combination of numerical control generation, accurate measurement, computer numerical processing, and digitized correction. Finally, the correctness and practicability of the digitized reverse correction method are proved through a reverse correction experiment. The experimental results show that the tooth surface geometric deviations meet the engineering requirements after two trial cuts and one correction.

Network-based approach to identify prognostic biomarkers for estrogen receptor-positive breast cancer treatment with tamoxifen.

PubMed

Liu, Rong; Guo, Cheng-Xian; Zhou, Hong-Hao

2015-01-01

This study aims to identify effective gene networks and prognostic biomarkers associated with estrogen receptor positive (ER+) breast cancer using human mRNA studies. Weighted gene coexpression network analysis was performed with a complex ER+ breast cancer transcriptome to investigate the function of networks and key genes in the prognosis of breast cancer. We found a significant correlation of an expression module with distant metastasis-free survival (HR = 2.25; 95% CI .21.03-4.88 in discovery set; HR = 1.78; 95% CI = 1.07-2.93 in validation set). This module contained genes enriched in the biological process of the M phase. From this module, we further identified and validated 5 hub genes (CDK1, DLGAP5, MELK, NUSAP1, and RRM2), the expression levels of which were strongly associated with poor survival. Highly expressed MELK indicated poor survival in luminal A and luminal B breast cancer molecular subtypes. This gene was also found to be associated with tamoxifen resistance. Results indicated that a network-based approach may facilitate the discovery of biomarkers for the prognosis of ER+ breast cancer and may also be used as a basis for establishing personalized therapies. Nevertheless, before the application of this approach in clinical settings, in vivo and in vitro experiments and multi-center randomized controlled clinical trials are still needed.

Fragment approach to constrained density functional theory calculations using Daubechies wavelets

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

Ratcliff, Laura E.; Genovese, Luigi; Mohr, Stephan

2015-06-21

In a recent paper, we presented a linear scaling Kohn-Sham density functional theory (DFT) code based on Daubechies wavelets, where a minimal set of localized support functions are optimized in situ and therefore adapted to the chemical properties of the molecular system. Thanks to the systematically controllable accuracy of the underlying basis set, this approach is able to provide an optimal contracted basis for a given system: accuracies for ground state energies and atomic forces are of the same quality as an uncontracted, cubic scaling approach. This basis set offers, by construction, a natural subset where the density matrix ofmore » the system can be projected. In this paper, we demonstrate the flexibility of this minimal basis formalism in providing a basis set that can be reused as-is, i.e., without reoptimization, for charge-constrained DFT calculations within a fragment approach. Support functions, represented in the underlying wavelet grid, of the template fragments are roto-translated with high numerical precision to the required positions and used as projectors for the charge weight function. We demonstrate the interest of this approach to express highly precise and efficient calculations for preparing diabatic states and for the computational setup of systems in complex environments.« less

Addressing standards of care in resource-limited settings.

PubMed

Dawson, Liza; Klingman, Karin L; Marrazzo, Jeanne

2014-01-01

: The choice between "best-known" standards of care (SOC) or "best available" standards as the control arm in a clinical trial is a fundamental dilemma in clinical research in resource-limited settings (RLS). When the health system is delivering less than an optimal level of care, using highest standard of care in a clinical trial may produce results that cannot be implemented or sustained locally. On the other hand, using interventions that are more feasible in the local setting may involve suboptimal care, and clinical outcomes may be affected. The need for improved standards in health systems in RLS, and the difficulty in securing them, has led many researchers advocate for policy changes at the national or international level to improve clinical care more systemically. SOC decisions in a clinical trial affect the level of benefit provided to study participants and the policy implications of the trial findings. SOC choices should provide high-quality care to help advance the health care system in host countries participating in the trial, but balancing the scientific and ethical objectives of SOC choices is difficult, and there is no single formula for selecting the appropriate SOC. Despite the challenges, well-designed and conducted clinical trials can and should make significant contributions to health systems in RLS.

Understanding density functional theory (DFT) and completing it in practice

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

Bagayoko, Diola

2014-12-15

We review some salient points in the derivation of density functional theory (DFT) and of the local density approximation (LDA) of it. We then articulate an understanding of DFT and LDA that seems to be ignored in the literature. We note the well-established failures of many DFT and LDA calculations to reproduce the measured energy gaps of finite systems and band gaps of semiconductors and insulators. We then illustrate significant differences between the results from self consistent calculations using single trial basis sets and those from computations following the Bagayoko, Zhao, and Williams (BZW) method, as enhanced by Ekuma andmore » Franklin (BZW-EF). Unlike the former, the latter calculations verifiably attain the absolute minima of the occupied energies, as required by DFT. These minima are one of the reasons for the agreement between their results and corresponding, experimental ones for the band gap and a host of other properties. Further, we note predictions of DFT BZW-EF calculations that have been confirmed by experiment. Our subsequent description of the BZW-EF method ends with the application of the Rayleigh theorem in the selection, among the several calculations the method requires, of the one whose results have a full, physics content ascribed to DFT. This application of the Rayleigh theorem adds to or completes DFT, in practice, to preserve the physical content of unoccupied, low energy levels. Discussions, including implications of the method, and a short conclusion follow the description of the method. The successive augmentation of the basis set in the BZW-EF method, needed for the application of the Rayleigh theorem, is also necessary in the search for the absolute minima of the occupied energies, in practice.« less

Narrowing the error in electron correlation calculations by basis set re-hierarchization and use of the unified singlet and triplet electron-pair extrapolation scheme: Application to a test set of 106 systems

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

Varandas, A. J. C., E-mail: varandas@uc.pt; Departamento de Física, Universidade Federal do Espírito Santo, 29075-910 Vitória; Pansini, F. N. N.

2014-12-14

A method previously suggested to calculate the correlation energy at the complete one-electron basis set limit by reassignment of the basis hierarchical numbers and use of the unified singlet- and triplet-pair extrapolation scheme is applied to a test set of 106 systems, some with up to 48 electrons. The approach is utilized to obtain extrapolated correlation energies from raw values calculated with second-order Møller-Plesset perturbation theory and the coupled-cluster singles and doubles excitations method, some of the latter also with the perturbative triples corrections. The calculated correlation energies have also been used to predict atomization energies within an additive scheme.more » Good agreement is obtained with the best available estimates even when the (d, t) pair of hierarchical numbers is utilized to perform the extrapolations. This conceivably justifies that there is no strong reason to exclude double-zeta energies in extrapolations, especially if the basis is calibrated to comply with the theoretical model.« less

The convergence of complete active space self-consistent-field configuration interaction including all single and double excitation energies to the complete basis set limit

NASA Astrophysics Data System (ADS)

Petersson, George A.; Malick, David K.; Frisch, Michael J.; Braunstein, Matthew

2006-07-01

Examination of the convergence of full valence complete active space self-consistent-field configuration interaction including all single and double excitation (CASSCF-CISD) energies with expansion of the one-electron basis set reveals a pattern very similar to the convergence of single determinant energies. Calculations on the lowest four singlet states and the lowest four triplet states of N2 with the sequence of n-tuple-ζ augmented polarized (nZaP) basis sets (n =2, 3, 4, 5, and 6) are used to establish the complete basis set limits. Full configuration-interaction (CI) and core electron contributions must be included for very accurate potential energy surfaces. However, a simple extrapolation scheme that has no adjustable parameters and requires nothing more demanding than CAS(10e -,8orb)-CISD/3ZaP calculations gives the Re, ωe, ωeXe, Te, and De for these eight states with rms errors of 0.0006Å, 4.43cm-1, 0.35cm-1, 0.063eV, and 0.018eV, respectively.

48 CFR 25.504-4 - Group award basis.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Group award basis. 25.504... SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Evaluating Foreign Offers-Supply Contracts 25.504-4 Group award basis... a group basis. Assume the Buy American Act applies and the acquisition cannot be set aside for small...

48 CFR 25.504-4 - Group award basis.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Group award basis. 25.504... SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Evaluating Foreign Offers-Supply Contracts 25.504-4 Group award basis... a group basis. Assume the Buy American Act applies and the acquisition cannot be set aside for small...

48 CFR 25.504-4 - Group award basis.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Group award basis. 25.504... SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Evaluating Foreign Offers-Supply Contracts 25.504-4 Group award basis... a group basis. Assume the Buy American statute applies and the acquisition cannot be set aside for...

48 CFR 25.504-4 - Group award basis.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Group award basis. 25.504... SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Evaluating Foreign Offers-Supply Contracts 25.504-4 Group award basis... a group basis. Assume the Buy American Act applies and the acquisition cannot be set aside for small...

48 CFR 25.504-4 - Group award basis.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Group award basis. 25.504... SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Evaluating Foreign Offers-Supply Contracts 25.504-4 Group award basis... a group basis. Assume the Buy American Act applies and the acquisition cannot be set aside for small...

Comparing community and specialty provider-based recruitment in a randomized clinical trial: clinical trial in fecal incontinence.

PubMed

Whitebird, Robin R; Bliss, Donna Zimmaro; Savik, Kay; Lowry, Ann; Jung, Hans-Joachim G

2010-12-01

Recruitment of participants to clinical trials remains a significant challenge, especially for research addressing topics of a sensitive nature such as fecal incontinence (FI). In the Fiber Study, a randomized controlled trial on symptom management for FI, we successfully enrolled 189 community-living adults through collaborations with specialty-based and community-based settings, each employing methods tailored to the organizational characteristics of their site. Results show that using the two settings increased racial and ethnic diversity of the sample and inclusion of informal caregivers. There were no differential effects on enrollment, final eligibility, or completion of protocol by site. Strategic collaborations with complementary sites can achieve sample recruitment goals for clinical trials on topics that are sensitive or known to be underreported. Copyright © 2010 Wiley Periodicals, Inc.

Early discharge hospital at home.

PubMed

Shepperd, Sasha; Doll, Helen; Broad, Joanna; Gladman, John; Iliffe, Steve; Langhorne, Peter; Richards, Suzanne; Martin, Finbarr; Harris, Roger

2009-01-21

'Early discharge hospital at home' is a service that provides active treatment by health care professionals in the patient's home for a condition that otherwise would require acute hospital in-patient care. If hospital at home were not available then the patient would remain in an acute hospital ward. To determine, in the context of a systematic review and meta-analysis, the effectiveness and cost of managing patients with early discharge hospital at home compared with in-patient hospital care. We searched the Cochrane Effective Practice and Organisation of Care (EPOC) Group Register , MEDLINE (1950 to 2008), EMBASE (1980 to 2008), CINAHL (1982 to 2008) and EconLit through to January 2008. We checked the reference lists of articles identified for potentially relevant articles. Randomised controlled trials recruiting patients aged 18 years and over. Studies comparing early discharge hospital at home with acute hospital in-patient care. Evaluations of obstetric, paediatric and mental health hospital at home schemes are excluded from this review. Two authors independently extracted data and assessed study quality. Our statistical analyses were done on an intention-to-treat basis. We requested individual patient data (IPD) from trialists, and relied on published data when we did not receive trial data sets or the IPD did not include the relevant outcomes. For the IPD meta-analysis, where at least one event was reported in both study groups in a trial, Cox regression models were used to calculate the log hazard ratio and its standard error for mortality and readmission separately for each data set. The calculated log hazard ratios were combined using fixed-effect inverse variance meta-analysis. Twenty-six trials were included in this review [n = 3967]; 21 were eligible for the IPD meta-analysis and 13 of the 21 trials contributed data [1899/2872; 66%]. For patients recovering from a stroke and elderly patients with a mix of conditions there was insufficient evidence of a difference in mortality between groups (adjusted HR 0.79, 95% CI 0.32 to 1.91; N = 494; and adjusted HR 1.06, 95% CI 0.69 to 1.61; N = 978). Readmission rates were significantly increased for elderly patients with a mix of conditions allocated to hospital at home (adjusted HR 1.57; 95% CI 1.10 to 2.24; N = 705). For patients recovering from a stroke and elderly patients with a mix of conditions respectively, significantly fewer people allocated to hospital at home were in residential care at follow up (RR 0.63; 95% CI 0.40 to 0.98; N = 4 trials; RR 0.69, 95% CI 0.48 to 0.99; N =3 trials). Patients reported increased satisfaction with early discharge hospital at home. There was insufficient evidence of a difference for readmission between groups in trials recruiting patients recovering from surgery. Evidence on cost savings was mixed. Despite increasing interest in the potential of early discharge hospital at home services as a cheaper alternative to in-patient care, this review provides insufficient objective evidence of economic benefit or improved health outcomes.

A geometrical correction for the inter- and intra-molecular basis set superposition error in Hartree-Fock and density functional theory calculations for large systems

NASA Astrophysics Data System (ADS)

Kruse, Holger; Grimme, Stefan

2012-04-01

A semi-empirical counterpoise-type correction for basis set superposition error (BSSE) in molecular systems is presented. An atom pair-wise potential corrects for the inter- and intra-molecular BSSE in supermolecular Hartree-Fock (HF) or density functional theory (DFT) calculations. This geometrical counterpoise (gCP) denoted scheme depends only on the molecular geometry, i.e., no input from the electronic wave-function is required and hence is applicable to molecules with ten thousands of atoms. The four necessary parameters have been determined by a fit to standard Boys and Bernadi counterpoise corrections for Hobza's S66×8 set of non-covalently bound complexes (528 data points). The method's target are small basis sets (e.g., minimal, split-valence, 6-31G*), but reliable results are also obtained for larger triple-ζ sets. The intermolecular BSSE is calculated by gCP within a typical error of 10%-30% that proves sufficient in many practical applications. The approach is suggested as a quantitative correction in production work and can also be routinely applied to estimate the magnitude of the BSSE beforehand. The applicability for biomolecules as the primary target is tested for the crambin protein, where gCP removes intramolecular BSSE effectively and yields conformational energies comparable to def2-TZVP basis results. Good mutual agreement is also found with Jensen's ACP(4) scheme, estimating the intramolecular BSSE in the phenylalanine-glycine-phenylalanine tripeptide, for which also a relaxed rotational energy profile is presented. A variety of minimal and double-ζ basis sets combined with gCP and the dispersion corrections DFT-D3 and DFT-NL are successfully benchmarked on the S22 and S66 sets of non-covalent interactions. Outstanding performance with a mean absolute deviation (MAD) of 0.51 kcal/mol (0.38 kcal/mol after D3-refit) is obtained at the gCP-corrected HF-D3/(minimal basis) level for the S66 benchmark. The gCP-corrected B3LYP-D3/6-31G* model chemistry yields MAD=0.68 kcal/mol, which represents a huge improvement over plain B3LYP/6-31G* (MAD=2.3 kcal/mol). Application of gCP-corrected B97-D3 and HF-D3 on a set of large protein-ligand complexes prove the robustness of the method. Analytical gCP gradients make optimizations of large systems feasible with small basis sets, as demonstrated for the inter-ring distances of 9-helicene and most of the complexes in Hobza's S22 test set. The method is implemented in a freely available FORTRAN program obtainable from the author's website.

Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion.

PubMed

Hill, S R; Carless, P A; Henry, D A; Carson, J L; Hebert, P C; McClelland, D B; Henderson, K M

2002-01-01

Most clinical practice guidelines recommend restrictive red cell transfusion practices with the goal of minimising exposure to allogeneic blood (from an unrelated donor). The purpose of this review is to compare clinical outcomes in patients randomised to restrictive versus liberal transfusion thresholds (triggers). To examine the evidence on the effect of transfusion thresholds, on the use of allogeneic and/or autologous blood, and the evidence for any effect on clinical outcomes. Trials were identified by: computer searches of OVID Medline (1966 to December 2000), Current Contents (1993 to Week 48 2000), and the Cochrane Controlled Trials Register (2000 Issue 4). References in identified trials and review articles were checked and authors contacted to identify any additional studies. Controlled trials in which patients were randomised to an intervention group or to a control group. Trials were included where the intervention groups were assigned on the basis of a clear transfusion "trigger", described as a haemoglobin (Hb) or haematocrit (Hct) level below which a RBC transfusion was to be administered. Trial quality was assessed using criteria proposed by Schulz et al. (1995). Relative risks of requiring allogeneic blood transfusion, transfused blood volumes and other clinical outcomes were pooled across trials using a random effects model. Ten trials were identified that reported outcomes for a total of 1780 patients. Restrictive transfusion strategies reduced the risk of receiving a red blood cell (RBC) transfusion by a relative 42% (RR=0.58: 95%CI=0.47,0.71). This equates to an average absolute risk reduction (ARR) of 40% (95%CI=24% to 56%). The volume of RBCs transfused was reduced on average by 0.93 units (95%CI=0.36,1.5 units). However, heterogeneity between these trials was statistically significant (p<0.00001) for these outcomes. Mortality, rates of cardiac events, morbidity, and length of hospital stay were unaffected. Trials were of poor methodological quality. The limited published evidence supports the use of restrictive transfusion triggers in patients who are free of serious cardiac disease. However, most of the data on clinical outcomes were generated by a single trial. The effects of conservative transfusion triggers on functional status, morbidity and mortality, particularly in patients with cardiac disease, need to be tested in further large clinical trials. In countries with inadequate screening of donor blood the data may constitute a stronger basis for avoiding transfusion with allogeneic red cells.

Accurate Gaussian basis sets for atomic and molecular calculations obtained from the generator coordinate method with polynomial discretization.

PubMed

Celeste, Ricardo; Maringolo, Milena P; Comar, Moacyr; Viana, Rommel B; Guimarães, Amanda R; Haiduke, Roberto L A; da Silva, Albérico B F

2015-10-01

Accurate Gaussian basis sets for atoms from H to Ba were obtained by means of the generator coordinate Hartree-Fock (GCHF) method based on a polynomial expansion to discretize the Griffin-Wheeler-Hartree-Fock equations (GWHF). The discretization of the GWHF equations in this procedure is based on a mesh of points not equally distributed in contrast with the original GCHF method. The results of atomic Hartree-Fock energies demonstrate the capability of these polynomial expansions in designing compact and accurate basis sets to be used in molecular calculations and the maximum error found when compared to numerical values is only 0.788 mHartree for indium. Some test calculations with the B3LYP exchange-correlation functional for N2, F2, CO, NO, HF, and HCN show that total energies within 1.0 to 2.4 mHartree compared to the cc-pV5Z basis sets are attained with our contracted bases with a much smaller number of polarization functions (2p1d and 2d1f for hydrogen and heavier atoms, respectively). Other molecular calculations performed here are also in very good accordance with experimental and cc-pV5Z results. The most important point to be mentioned here is that our generator coordinate basis sets required only a tiny fraction of the computational time when compared to B3LYP/cc-pV5Z calculations.

Flat bases of invariant polynomials and P-matrices of E{sub 7} and E{sub 8}

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

Talamini, Vittorino

2010-02-15

Let G be a compact group of linear transformations of a Euclidean space V. The G-invariant C{sup {infinity}} functions can be expressed as C{sup {infinity}} functions of a finite basic set of G-invariant homogeneous polynomials, sometimes called an integrity basis. The mathematical description of the orbit space V/G depends on the integrity basis too: it is realized through polynomial equations and inequalities expressing rank and positive semidefiniteness conditions of the P-matrix, a real symmetric matrix determined by the integrity basis. The choice of the basic set of G-invariant homogeneous polynomials forming an integrity basis is not unique, so it ismore » not unique the mathematical description of the orbit space too. If G is an irreducible finite reflection group, Saito et al. [Commun. Algebra 8, 373 (1980)] characterized some special basic sets of G-invariant homogeneous polynomials that they called flat. They also found explicitly the flat basic sets of invariant homogeneous polynomials of all the irreducible finite reflection groups except of the two largest groups E{sub 7} and E{sub 8}. In this paper the flat basic sets of invariant homogeneous polynomials of E{sub 7} and E{sub 8} and the corresponding P-matrices are determined explicitly. Using the results here reported one is able to determine easily the P-matrices corresponding to any other integrity basis of E{sub 7} or E{sub 8}. From the P-matrices one may then write down the equations and inequalities defining the orbit spaces of E{sub 7} and E{sub 8} relatively to a flat basis or to any other integrity basis. The results here obtained may be employed concretely to study analytically the symmetry breaking in all theories where the symmetry group is one of the finite reflection groups E{sub 7} and E{sub 8} or one of the Lie groups E{sub 7} and E{sub 8} in their adjoint representations.« less

Enhancing decision making about participation in cancer clinical trials: development of a question prompt list

PubMed Central

Brown, Richard F.; Shuk, Elyse; Leighl, Natasha; Butow, Phyllis; Ostroff, Jamie; Edgerson, Shawna; Tattersall, Martin

2016-01-01

Purpose Slow accrual to cancer clinical trials impedes the progress of effective new cancer treatments. Poor physician–patient communication has been identified as a key contributor to low trial accrual. Question prompt lists (QPLs) have demonstrated a significant promise in facilitating communication in general, surgical, and palliative oncology settings. These simple patient interventions have not been tested in the oncology clinical trial setting. We aimed to develop a targeted QPL for clinical trials (QPL-CT). Method Lung, breast, and prostate cancer patients who either had (trial experienced) or had not (trial naive) participated in a clinical trial were invited to join focus groups to help develop and explore the acceptability of a QPL-CT. Focus groups were audio-recorded and transcribed. A research team, including a qualitative data expert, analyzed these data to explore patients’ decision-making processes and views about the utility of the QPL-CT prompt to aid in trial decision making. Results Decision making was influenced by the outcome of patients’ comparative assessment of perceived risks versus benefits of a trial, and the level of trust patients had in their doctors’ recommendation about the trial. Severity of a patient’s disease influenced trial decision making only for trial-naive patients. Conclusion Although patients were likely to prefer a paternalistic decision-making style, they expressed valuation of the QPL as an aid to decision making. QPL-CT utility extended beyond the actual consultation to include roles both before and after the clinical trial discussion. PMID:20593202

Spectroscopic properties of Arx-Zn and Arx-Ag+ (x = 1,2) van der Waals complexes

NASA Astrophysics Data System (ADS)

Oyedepo, Gbenga A.; Peterson, Charles; Schoendorff, George; Wilson, Angela K.

2013-03-01

Potential energy curves have been constructed using coupled cluster with singles, doubles, and perturbative triple excitations (CCSD(T)) in combination with all-electron and pseudopotential-based multiply augmented correlation consistent basis sets [m-aug-cc-pV(n + d)Z; m = singly, doubly, triply, n = D,T,Q,5]. The effect of basis set superposition error on the spectroscopic properties of Ar-Zn, Ar2-Zn, Ar-Ag+, and Ar2-Ag+ van der Waals complexes was examined. The diffuse functions of the doubly and triply augmented basis sets have been constructed using the even-tempered expansion. The a posteriori counterpoise scheme of Boys and Bernardi and its generalized variant by Valiron and Mayer has been utilized to correct for basis set superposition error (BSSE) in the calculated spectroscopic properties for diatomic and triatomic species. It is found that even at the extrapolated complete basis set limit for the energetic properties, the pseudopotential-based calculations still suffer from significant BSSE effects unlike the all-electron basis sets. This indicates that the quality of the approximations used in the design of pseudopotentials could have major impact on a seemingly valence-exclusive effect like BSSE. We confirm the experimentally determined equilibrium internuclear distance (re), binding energy (De), harmonic vibrational frequency (ωe), and C1Π ← X1Σ transition energy for ArZn and also predict the spectroscopic properties for the low-lying excited states of linear Ar2-Zn (X1Σg, 3Πg, 1Πg), Ar-Ag+ (X1Σ, 3Σ, 3Π, 3Δ, 1Σ, 1Π, 1Δ), and Ar2-Ag+ (X1Σg, 3Σg, 3Πg, 3Δg, 1Σg, 1Πg, 1Δg) complexes, using the CCSD(T) and MR-CISD + Q methods, to aid in their experimental characterizations.

A Randomised Controlled Trial of the Use of a Piece of Commercial Software for the Acquisition of Reading Skills

ERIC Educational Resources Information Center

Khan, Muhammad Ahmad; Gorard, Stephen

2012-01-01

We report here the overall results of a cluster randomised controlled trial of the use of computer-aided instruction with 672 Year 7 pupils in 23 secondary school classes in the north of England. A new piece of commercial software, claimed on the basis of publisher testing to be effective in improving reading after just six weeks of use in the…

Clinical trial design for orthodontists.

PubMed

Pandis, Nikolaos; Cobourne, Martyn T

2013-06-01

High-quality research should form the basis of all clinical practice. Randomized controlled trials currently provide the gold standard for investigating the effectiveness of treatment interventions and these are increasingly being used in orthodontics. Here we discuss the reasons why this form of investigation provides the most useful evidence for assessing treatment outcome. The methods available to achieve true randomization, a fundamental component in the design of these trials, are also discussed. In addition, we focus on how to minimize bias in clinical research, not only during the design and management of a trial, but also when disseminating results. We focus on the importance of using control groups correctly and describe methods that are available to adequately power a trial. Finally, we emphasise the importance of accurate and transparent reporting, which facilitates correct communication and assessment of the evidence.

A projection-free method for representing plane-wave DFT results in an atom-centered basis

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

Dunnington, Benjamin D.; Schmidt, J. R., E-mail: schmidt@chem.wisc.edu

2015-09-14

Plane wave density functional theory (DFT) is a powerful tool for gaining accurate, atomic level insight into bulk and surface structures. Yet, the delocalized nature of the plane wave basis set hinders the application of many powerful post-computation analysis approaches, many of which rely on localized atom-centered basis sets. Traditionally, this gap has been bridged via projection-based techniques from a plane wave to atom-centered basis. We instead propose an alternative projection-free approach utilizing direct calculation of matrix elements of the converged plane wave DFT Hamiltonian in an atom-centered basis. This projection-free approach yields a number of compelling advantages, including strictmore » orthonormality of the resulting bands without artificial band mixing and access to the Hamiltonian matrix elements, while faithfully preserving the underlying DFT band structure. The resulting atomic orbital representation of the Kohn-Sham wavefunction and Hamiltonian provides a gateway to a wide variety of analysis approaches. We demonstrate the utility of the approach for a diverse set of chemical systems and example analysis approaches.« less

Strategies to improve retention in randomised trials.

PubMed

Brueton, Valerie C; Tierney, Jayne; Stenning, Sally; Harding, Seeromanie; Meredith, Sarah; Nazareth, Irwin; Rait, Greta

2013-12-03

Loss to follow-up from randomised trials can introduce bias and reduce study power, affecting the generalisability, validity and reliability of results. Many strategies are used to reduce loss to follow-up and improve retention but few have been formally evaluated. To quantify the effect of strategies to improve retention on the proportion of participants retained in randomised trials and to investigate if the effect varied by trial strategy and trial setting. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PreMEDLINE, EMBASE, PsycINFO, DARE, CINAHL, Campbell Collaboration's Social, Psychological, Educational and Criminological Trials Register, and ERIC. We handsearched conference proceedings and publication reference lists for eligible retention trials. We also surveyed all UK Clinical Trials Units to identify further studies. We included eligible retention trials of randomised or quasi-randomised evaluations of strategies to increase retention that were embedded in 'host' randomised trials from all disease areas and healthcare settings. We excluded studies aiming to increase treatment compliance. We contacted authors to supplement or confirm data that we had extracted. For retention trials, we recorded data on the method of randomisation, type of strategy evaluated, comparator, primary outcome, planned sample size, numbers randomised and numbers retained. We used risk ratios (RR) to evaluate the effectiveness of the addition of strategies to improve retention. We assessed heterogeneity between trials using the Chi(2) and I(2) statistics. For main trials that hosted retention trials, we extracted data on disease area, intervention, population, healthcare setting, sequence generation and allocation concealment. We identified 38 eligible retention trials. Included trials evaluated six broad types of strategies to improve retention. These were incentives, communication strategies, new questionnaire format, participant case management, behavioural and methodological interventions. For 34 of the included trials, retention was response to postal and electronic questionnaires with or without medical test kits. For four trials, retention was the number of participants remaining in the trial. Included trials were conducted across a spectrum of disease areas, countries, healthcare and community settings. Strategies that improved trial retention were addition of monetary incentives compared with no incentive for return of trial-related postal questionnaires (RR 1.18; 95% CI 1.09 to 1.28, P value < 0.0001), addition of an offer of monetary incentive compared with no offer for return of electronic questionnaires (RR 1.25; 95% CI 1.14 to 1.38, P value < 0.00001) and an offer of a GBP20 voucher compared with GBP10 for return of postal questionnaires and biomedical test kits (RR 1.12; 95% CI 1.04 to 1.22, P value < 0.005). The evidence that shorter questionnaires are better than longer questionnaires was unclear (RR 1.04; 95% CI 1.00 to 1.08, P value = 0.07) and the evidence for questionnaires relevant to the disease/condition was also unclear (RR 1.07; 95% CI 1.01 to 1.14). Although each was based on the results of a single trial, recorded delivery of questionnaires seemed to be more effective than telephone reminders (RR 2.08; 95% CI 1.11 to 3.87, P value = 0.02) and a 'package' of postal communication strategies with reminder letters appeared to be better than standard procedures (RR 1.43; 95% CI 1.22 to 1.67, P value < 0.0001). An open trial design also appeared more effective than a blind trial design for return of questionnaires in one fracture prevention trial (RR 1.37; 95% CI 1.16 to 1.63, P value = 0.0003).There was no good evidence that the addition of a non-monetary incentive, an offer of a non-monetary incentive, 'enhanced' letters, letters delivered by priority post, additional reminders, or questionnaire question order either increased or decreased trial questionnaire response/retention. There was also no evidence that a telephone survey was either more or less effective than a monetary incentive and a questionnaire. As our analyses are based on single trials, the effect on questionnaire response of using offers of charity donations, sending reminders to trial sites and when a questionnaire is sent, may need further evaluation. Case management and behavioural strategies used for trial retention may also warrant further evaluation. Most of the retention trials that we identified evaluated questionnaire response. There were few evaluations of ways to improve participants returning to trial sites for trial follow-up. Monetary incentives and offers of monetary incentives increased postal and electronic questionnaire response. Some other strategies evaluated in single trials looked promising but need further evaluation. Application of the findings of this review would depend on trial setting, population, disease area, data collection and follow-up procedures.

Density functional theory study of the interaction of vinyl radical, ethyne, and ethene with benzene, aimed to define an affordable computational level to investigate stability trends in large van der Waals complexes

NASA Astrophysics Data System (ADS)

Maranzana, Andrea; Giordana, Anna; Indarto, Antonius; Tonachini, Glauco; Barone, Vincenzo; Causà, Mauro; Pavone, Michele

2013-12-01

Our purpose is to identify a computational level sufficiently dependable and affordable to assess trends in the interaction of a variety of radical or closed shell unsaturated hydro-carbons A adsorbed on soot platelet models B. These systems, of environmental interest, would unavoidably have rather large sizes, thus prompting to explore in this paper the performances of relatively low-level computational methods and compare them with higher-level reference results. To this end, the interaction of three complexes between non-polar species, vinyl radical, ethyne, or ethene (A) with benzene (B) is studied, since these species, involved themselves in growth processes of polycyclic aromatic hydrocarbons (PAHs) and soot particles, are small enough to allow high-level reference calculations of the interaction energy ΔEAB. Counterpoise-corrected interaction energies ΔEAB are used at all stages. (1) Density Functional Theory (DFT) unconstrained optimizations of the A-B complexes are carried out, using the B3LYP-D, ωB97X-D, and M06-2X functionals, with six basis sets: 6-31G(d), 6-311 (2d,p), and 6-311++G(3df,3pd); aug-cc-pVDZ and aug-cc-pVTZ; N07T. (2) Then, unconstrained optimizations by Møller-Plesset second order Perturbation Theory (MP2), with each basis set, allow subsequent single point Coupled Cluster Singles Doubles and perturbative estimate of the Triples energy computations with the same basis sets [CCSD(T)//MP2]. (3) Based on an additivity assumption of (i) the estimated MP2 energy at the complete basis set limit [EMP2/CBS] and (ii) the higher-order correlation energy effects in passing from MP2 to CCSD(T) at the aug-cc-pVTZ basis set, ΔECC-MP, a CCSD(T)/CBS estimate is obtained and taken as a computational energy reference. At DFT, variations in ΔEAB with basis set are not large for the title molecules, and the three functionals perform rather satisfactorily even with rather small basis sets [6-31G(d) and N07T], exhibiting deviation from the computational reference of less than 1 kcal mol-1. The zero-point vibrational energy corrected estimates Δ(EAB+ZPE), obtained with the three functionals and the 6-31G(d) and N07T basis sets, are compared with experimental D0 measures, when available. In particular, this comparison is finally extended to the naphthalene and coronene dimers and to three π-π associations of different PAHs (R, made by 10, 16, or 24 C atoms) and P (80 C atoms).

Density functional theory study of the interaction of vinyl radical, ethyne, and ethene with benzene, aimed to define an affordable computational level to investigate stability trends in large van der Waals complexes.

PubMed

Maranzana, Andrea; Giordana, Anna; Indarto, Antonius; Tonachini, Glauco; Barone, Vincenzo; Causà, Mauro; Pavone, Michele

2013-12-28

Our purpose is to identify a computational level sufficiently dependable and affordable to assess trends in the interaction of a variety of radical or closed shell unsaturated hydro-carbons A adsorbed on soot platelet models B. These systems, of environmental interest, would unavoidably have rather large sizes, thus prompting to explore in this paper the performances of relatively low-level computational methods and compare them with higher-level reference results. To this end, the interaction of three complexes between non-polar species, vinyl radical, ethyne, or ethene (A) with benzene (B) is studied, since these species, involved themselves in growth processes of polycyclic aromatic hydrocarbons (PAHs) and soot particles, are small enough to allow high-level reference calculations of the interaction energy ΔEAB. Counterpoise-corrected interaction energies ΔEAB are used at all stages. (1) Density Functional Theory (DFT) unconstrained optimizations of the A-B complexes are carried out, using the B3LYP-D, ωB97X-D, and M06-2X functionals, with six basis sets: 6-31G(d), 6-311 (2d,p), and 6-311++G(3df,3pd); aug-cc-pVDZ and aug-cc-pVTZ; N07T. (2) Then, unconstrained optimizations by Møller-Plesset second order Perturbation Theory (MP2), with each basis set, allow subsequent single point Coupled Cluster Singles Doubles and perturbative estimate of the Triples energy computations with the same basis sets [CCSD(T)//MP2]. (3) Based on an additivity assumption of (i) the estimated MP2 energy at the complete basis set limit [EMP2/CBS] and (ii) the higher-order correlation energy effects in passing from MP2 to CCSD(T) at the aug-cc-pVTZ basis set, ΔECC-MP, a CCSD(T)/CBS estimate is obtained and taken as a computational energy reference. At DFT, variations in ΔEAB with basis set are not large for the title molecules, and the three functionals perform rather satisfactorily even with rather small basis sets [6-31G(d) and N07T], exhibiting deviation from the computational reference of less than 1 kcal mol(-1). The zero-point vibrational energy corrected estimates Δ(EAB+ZPE), obtained with the three functionals and the 6-31G(d) and N07T basis sets, are compared with experimental D0 measures, when available. In particular, this comparison is finally extended to the naphthalene and coronene dimers and to three π-π associations of different PAHs (R, made by 10, 16, or 24 C atoms) and P (80 C atoms).

Evaluating the influence of goal setting on intravenous catheterization skill acquisition and transfer in a hybrid simulation training context.

PubMed

Brydges, Ryan; Mallette, Claire; Pollex, Heather; Carnahan, Heather; Dubrowski, Adam

2012-08-01

Educators often simplify complex tasks by setting learning objectives that focus trainees on isolated skills rather than the holistic task. We designed 2 sets of learning objectives for intravenous catheterization using goal setting theory. We hypothesized that setting holistic goals related to technical, cognitive, and communication skills would result in superior holistic performance, whereas setting isolated goals related to technical skills would result in superior technical performance. We randomly assigned practicing health care professionals to set holistic (n = 14) or isolated (n = 15) goals. All watched an instructional video and studied a list of 9 goals specific to their group. Participants practiced independently in a hybrid simulation (standardized patient combined with an arm simulator). The first and the last practice trials were videotaped for analysis. One-week later, participants completed a transfer test in another hybrid simulation scenario. Blinded experts evaluated performance on all 3 trials using the Direct Observation of Procedural Skills tool. The holistic group scored higher than the isolated group on the holistic Direct Observation of Procedural Skills score for all 3 trials [mean (SD), 45.0 (9.16) vs. 38.4 (9.17); P = 0.01]. The isolated group did not perform better than the holistic group on the technical skills score [10.3 (2.73) vs. 11.6 (3.01); P = 0.11]. Our results suggest that asking learners to set holistic goals did not interfere with their attaining competent holistic and technical skills during hybrid simulation training. This exploratory trial provides preliminary evidence for how to consider integrating hybrid simulation into medical curricula and for the design of learning goals in simulation-based education.

Decoding intentions from movement kinematics

PubMed Central

Cavallo, Andrea; Koul, Atesh; Ansuini, Caterina; Capozzi, Francesca; Becchio, Cristina

2016-01-01

How do we understand the intentions of other people? There has been a longstanding controversy over whether it is possible to understand others’ intentions by simply observing their movements. Here, we show that indeed movement kinematics can form the basis for intention detection. By combining kinematics and psychophysical methods with classification and regression tree (CART) modeling, we found that observers utilized a subset of discriminant kinematic features over the total kinematic pattern in order to detect intention from observation of simple motor acts. Intention discriminability covaried with movement kinematics on a trial-by-trial basis, and was directly related to the expression of discriminative features in the observed movements. These findings demonstrate a definable and measurable relationship between the specific features of observed movements and the ability to discriminate intention, providing quantitative evidence of the significance of movement kinematics for anticipating others’ intentional actions. PMID:27845434

Identifying Emotions on the Basis of Neural Activation

PubMed Central

Kassam, Karim S.; Markey, Amanda R.; Cherkassky, Vladimir L.; Loewenstein, George; Just, Marcel Adam

2013-01-01

We attempt to determine the discriminability and organization of neural activation corresponding to the experience of specific emotions. Method actors were asked to self-induce nine emotional states (anger, disgust, envy, fear, happiness, lust, pride, sadness, and shame) while in an fMRI scanner. Using a Gaussian Naïve Bayes pooled variance classifier, we demonstrate the ability to identify specific emotions experienced by an individual at well over chance accuracy on the basis of: 1) neural activation of the same individual in other trials, 2) neural activation of other individuals who experienced similar trials, and 3) neural activation of the same individual to a qualitatively different type of emotion induction. Factor analysis identified valence, arousal, sociality, and lust as dimensions underlying the activation patterns. These results suggest a structure for neural representations of emotion and inform theories of emotional processing. PMID:23840392

Identifying Emotions on the Basis of Neural Activation.

PubMed

Kassam, Karim S; Markey, Amanda R; Cherkassky, Vladimir L; Loewenstein, George; Just, Marcel Adam

2013-01-01

We attempt to determine the discriminability and organization of neural activation corresponding to the experience of specific emotions. Method actors were asked to self-induce nine emotional states (anger, disgust, envy, fear, happiness, lust, pride, sadness, and shame) while in an fMRI scanner. Using a Gaussian Naïve Bayes pooled variance classifier, we demonstrate the ability to identify specific emotions experienced by an individual at well over chance accuracy on the basis of: 1) neural activation of the same individual in other trials, 2) neural activation of other individuals who experienced similar trials, and 3) neural activation of the same individual to a qualitatively different type of emotion induction. Factor analysis identified valence, arousal, sociality, and lust as dimensions underlying the activation patterns. These results suggest a structure for neural representations of emotion and inform theories of emotional processing.

Automated clinical trial eligibility prescreening: increasing the efficiency of patient identification for clinical trials in the emergency department

PubMed Central

Ni, Yizhao; Kennebeck, Stephanie; Dexheimer, Judith W; McAneney, Constance M; Tang, Huaxiu; Lingren, Todd; Li, Qi; Zhai, Haijun; Solti, Imre

2015-01-01

Objectives (1) To develop an automated eligibility screening (ES) approach for clinical trials in an urban tertiary care pediatric emergency department (ED); (2) to assess the effectiveness of natural language processing (NLP), information extraction (IE), and machine learning (ML) techniques on real-world clinical data and trials. Data and methods We collected eligibility criteria for 13 randomly selected, disease-specific clinical trials actively enrolling patients between January 1, 2010 and August 31, 2012. In parallel, we retrospectively selected data fields including demographics, laboratory data, and clinical notes from the electronic health record (EHR) to represent profiles of all 202795 patients visiting the ED during the same period. Leveraging NLP, IE, and ML technologies, the automated ES algorithms identified patients whose profiles matched the trial criteria to reduce the pool of candidates for staff screening. The performance was validated on both a physician-generated gold standard of trial–patient matches and a reference standard of historical trial–patient enrollment decisions, where workload, mean average precision (MAP), and recall were assessed. Results Compared with the case without automation, the workload with automated ES was reduced by 92% on the gold standard set, with a MAP of 62.9%. The automated ES achieved a 450% increase in trial screening efficiency. The findings on the gold standard set were confirmed by large-scale evaluation on the reference set of trial–patient matches. Discussion and conclusion By exploiting the text of trial criteria and the content of EHRs, we demonstrated that NLP-, IE-, and ML-based automated ES could successfully identify patients for clinical trials. PMID:25030032

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.

Orthonormal vector polynomials in a unit circle, Part I: Basis set derived from gradients of Zernike polynomials.

PubMed

Zhao, Chunyu; Burge, James H

2007-12-24

Zernike polynomials provide a well known, orthogonal set of scalar functions over a circular domain, and are commonly used to represent wavefront phase or surface irregularity. A related set of orthogonal functions is given here which represent vector quantities, such as mapping distortion or wavefront gradient. These functions are generated from gradients of Zernike polynomials, made orthonormal using the Gram- Schmidt technique. This set provides a complete basis for representing vector fields that can be defined as a gradient of some scalar function. It is then efficient to transform from the coefficients of the vector functions to the scalar Zernike polynomials that represent the function whose gradient was fit. These new vector functions have immediate application for fitting data from a Shack-Hartmann wavefront sensor or for fitting mapping distortion for optical testing. A subsequent paper gives an additional set of vector functions consisting only of rotational terms with zero divergence. The two sets together provide a complete basis that can represent all vector distributions in a circular domain.

30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial.

PubMed

Ringleb, P A; Allenberg, J; Brückmann, H; Eckstein, H-H; Fraedrich, G; Hartmann, M; Hennerici, M; Jansen, O; Klein, G; Kunze, A; Marx, P; Niederkorn, K; Schmiedt, W; Solymosi, L; Stingele, R; Zeumer, H; Hacke, W

2006-10-07

Carotid endarterectomy is effective in stroke prevention for patients with severe symptomatic carotid-artery stenosis, and carotid-artery stenting has been widely used as alternative treatment. Since equivalence or superiority has not been convincingly shown for either treatment, we aimed to compare the two. 1200 patients with symptomatic carotid-artery stenosis were randomly assigned within 180 days of transient ischaemic attack or moderate stroke (modified Rankin scale score of < or =3) carotid-artery stenting (n=605) or carotid endarterectomy (n=595). The primary endpoint of this hospital-based study was ipsilateral ischaemic stroke or death from time of randomisation to 30 days after the procedure. The non-inferiority margin was defined as less than 2.5% on the basis of an expected event rate of 5%. Analyses were on an intention-to-treat basis. This trial is registered at Current Controlled Trials with the international standard randomised controlled trial number ISRCTN57874028. 1183 patients were included in the analysis. The rate of death or ipsilateral ischaemic stroke from randomisation to 30 days after the procedure was 6.84% with carotid-artery stenting and 6.34% with carotid endarterectomy (absolute difference 0.51%, 90% CI -1.89% to 2.91%). The one-sided p value for non-inferiority is 0.09. SPACE failed to prove non-inferiority of carotid-artery stenting compared with carotid endarterectomy for the periprocedural complication rate. The results of this trial do not justify the widespread use in the short-term of carotid-artery stenting for treatment of carotid-artery stenoses. Results at 6-24 months are awaited.

Employing general fit-bases for construction of potential energy surfaces with an adaptive density-guided approach

NASA Astrophysics Data System (ADS)

Klinting, Emil Lund; Thomsen, Bo; Godtliebsen, Ian Heide; Christiansen, Ove

2018-02-01

We present an approach to treat sets of general fit-basis functions in a single uniform framework, where the functional form is supplied on input, i.e., the use of different functions does not require new code to be written. The fit-basis functions can be used to carry out linear fits to the grid of single points, which are generated with an adaptive density-guided approach (ADGA). A non-linear conjugate gradient method is used to optimize non-linear parameters if such are present in the fit-basis functions. This means that a set of fit-basis functions with the same inherent shape as the potential cuts can be requested and no other choices with regards to the fit-basis functions need to be taken. The general fit-basis framework is explored in relation to anharmonic potentials for model systems, diatomic molecules, water, and imidazole. The behaviour and performance of Morse and double-well fit-basis functions are compared to that of polynomial fit-basis functions for unsymmetrical single-minimum and symmetrical double-well potentials. Furthermore, calculations for water and imidazole were carried out using both normal coordinates and hybrid optimized and localized coordinates (HOLCs). Our results suggest that choosing a suitable set of fit-basis functions can improve the stability of the fitting routine and the overall efficiency of potential construction by lowering the number of single point calculations required for the ADGA. It is possible to reduce the number of terms in the potential by choosing the Morse and double-well fit-basis functions. These effects are substantial for normal coordinates but become even more pronounced if HOLCs are used.

Analytical energy gradients for explicitly correlated wave functions. I. Explicitly correlated second-order Møller-Plesset perturbation theory

NASA Astrophysics Data System (ADS)

Győrffy, Werner; Knizia, Gerald; Werner, Hans-Joachim

2017-12-01

We present the theory and algorithms for computing analytical energy gradients for explicitly correlated second-order Møller-Plesset perturbation theory (MP2-F12). The main difficulty in F12 gradient theory arises from the large number of two-electron integrals for which effective two-body density matrices and integral derivatives need to be calculated. For efficiency, the density fitting approximation is used for evaluating all two-electron integrals and their derivatives. The accuracies of various previously proposed MP2-F12 approximations [3C, 3C(HY1), 3*C(HY1), and 3*A] are demonstrated by computing equilibrium geometries for a set of molecules containing first- and second-row elements, using double-ζ to quintuple-ζ basis sets. Generally, the convergence of the bond lengths and angles with respect to the basis set size is strongly improved by the F12 treatment, and augmented triple-ζ basis sets are sufficient to closely approach the basis set limit. The results obtained with the different approximations differ only very slightly. This paper is the first step towards analytical gradients for coupled-cluster singles and doubles with perturbative treatment of triple excitations, which will be presented in the second part of this series.

Simplified DFT methods for consistent structures and energies of large systems

NASA Astrophysics Data System (ADS)

Caldeweyher, Eike; Gerit Brandenburg, Jan

2018-05-01

Kohn–Sham density functional theory (DFT) is routinely used for the fast electronic structure computation of large systems and will most likely continue to be the method of choice for the generation of reliable geometries in the foreseeable future. Here, we present a hierarchy of simplified DFT methods designed for consistent structures and non-covalent interactions of large systems with particular focus on molecular crystals. The covered methods are a minimal basis set Hartree–Fock (HF-3c), a small basis set screened exchange hybrid functional (HSE-3c), and a generalized gradient approximated functional evaluated in a medium-sized basis set (B97-3c), all augmented with semi-classical correction potentials. We give an overview on the methods design, a comprehensive evaluation on established benchmark sets for geometries and lattice energies of molecular crystals, and highlight some realistic applications on large organic crystals with several hundreds of atoms in the primitive unit cell.

A practical radial basis function equalizer.

PubMed

Lee, J; Beach, C; Tepedelenlioglu, N

1999-01-01

A radial basis function (RBF) equalizer design process has been developed in which the number of basis function centers used is substantially fewer than conventionally required. The reduction of centers is accomplished in two-steps. First an algorithm is used to select a reduced set of centers that lie close to the decision boundary. Then the centers in this reduced set are grouped, and an average position is chosen to represent each group. Channel order and delay, which are determining factors in setting the initial number of centers, are estimated from regression analysis. In simulation studies, an RBF equalizer with more than 2000-to-1 reduction in centers performed as well as the RBF equalizer without reduction in centers, and better than a conventional linear equalizer.

High rate composting of herbal pharmaceutical industry solid waste.

PubMed

Ali, M; Duba, K S; Kalamdhad, A S; Bhatia, A; Khursheed, A; Kazmi, A A; Ahmed, N

2012-01-01

High rate composting studies of hard to degrade herbal wastes were conducted in a 3.5 m(3) capacity rotary drum composter. Studies were spread out in four trials: In trial 1 and 2, one and two turns per day rotation was observed, respectively, by mixing of herbal industry waste with cattle (buffalo) manure at a ratio of 3:1 on wet weight basis. In trial 3 inocula was added in raw waste to enhance the degradation and in trial 4 composting of a mixture of vegetable market waste and herbal waste was conducted at one turn per day. Results demonstrated that the operation of the rotary drum at one turn a day (trial 1) could provide the most conducive composting conditions and co-composting (trial 4) gave better quality compost in terms of temperature, moisture, nitrogen, and Solvita maturity index. In addition a FT-IR study also revealed that trial 1 and trial 4 gave quality compost in terms of stability and maturity due to the presence of more intense peaks in the aromatic region and less intense peaks were found in the aliphatic region compared with trial 2 and trial 3.

Digital breast tomosynthesis plus synthesised images versus standard full-field digital mammography in population-based screening (TOSYMA): protocol of a randomised controlled trial.

PubMed

Weigel, Stefanie; Gerss, Joachim; Hense, Hans-Werner; Krischke, Miriam; Sommer, Alexander; Czwoydzinski, Jörg; Lenzen, Horst; Kerschke, Laura; Spieker, Karin; Dickmaenken, Stefanie; Baier, Sonja; Urban, Marc; Hecht, Gerold; Heidinger, Oliver; Kieschke, Joachim; Heindel, Walter

2018-05-14

Development of digital breast tomosynthesis (DBT) provides a technology that generates three-dimensional data sets, thus reducing the pitfalls of overlapping breast tissue. Observational studies suggest that the combination of two-dimensional (2D) digital mammography and DBT increases diagnostic accuracy. However, because of duplicate exposure, this comes at the cost of an augmented radiation dose. This undesired adverse impact can be avoided by using synthesised 2D images reconstructed from the DBT data (s2D).We designed a diagnostic superiority trial on a high level of evidence with the aim of providing a comparison of screening efficacy parameters resulting from DBT+s2D versus the current screening standard 2D full-field digital mammography (FFDM) in a multicentre and multivendor setting on the basis of the quality-controlled, population-based, biennial mammography screening programme in Germany. 80 000 women in the eligible age 50-69 years attending the routine mammography screening programme and willing to participate in the TOSYMA trial will be assigned by 1:1 randomisation to either the intervention arm (DBT+s2D) or the control arm (FFDM) during a 12-month recruitment period in screening units of North Rhine-Westphalia and Lower Saxony. State cancer registries will provide the follow-up of interval cancers.Primary endpoints are the detection rate of invasive breast cancers at screening examination and the cumulative incidence of interval cancers in the 2 years after a negative examination. Secondary endpoints are the detection rate of ductal carcinoma in situ and of tumour size T1, the recall rate for assessment, the positive predictive value of recall and the cumulative 12-month incidence of interval cancers. An adaptive statistical design with one interim analysis provides the option to modify the design. This protocol has been approved by the local medical ethical committee (2016-132-f-S). Results will be submitted to international peer-reviewed journals. NCT03377036; 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 Topological Basis Realization for Six Qubits and the Corresponding Heisenberg Spin -{1/2} Chain Model

NASA Astrophysics Data System (ADS)

Yang, Qi; Cao, Yue; Chen, Shiyin; Teng, Yue; Meng, Yanli; Wang, Gangcheng; Sun, Chunfang; Xue, Kang

2018-03-01

In this paper, we construct a new set of orthonormal topological basis states for six qubits with the topological single loop d = 2. By acting on the subspace, we get a new five-dimensional (5D) reduced matrix. In addition, it is shown that the Heisenberg XXX spin-1/2 chain of six qubits can be constructed from the Temperley-Lieb algebra (TLA) generator, both the energy ground state and the spin singlet states of the system can be described by the set of topological basis states.

Use of an auxiliary basis set to describe the polarization in the fragment molecular orbital method

NASA Astrophysics Data System (ADS)

Fedorov, Dmitri G.; Kitaura, Kazuo

2014-03-01

We developed a dual basis approach within the fragment molecular orbital formalism enabling efficient and accurate use of large basis sets. The method was tested on water clusters and polypeptides and applied to perform geometry optimization of chignolin (PDB: 1UAO) in solution at the level of DFT/6-31++G∗∗, obtaining a structure in agreement with experiment (RMSD of 0.4526 Å). The polarization in polypeptides is discussed with a comparison of the α-helix and β-strand.