Near-optimal alternative generation using modified hit-and-run sampling for non-linear, non-convex problems

NASA Astrophysics Data System (ADS)

Rosenberg, D. E.; Alafifi, A.

2016-12-01

Water resources systems analysis often focuses on finding optimal solutions. Yet an optimal solution is optimal only for the modelled issues and managers often seek near-optimal alternatives that address un-modelled objectives, preferences, limits, uncertainties, and other issues. Early on, Modelling to Generate Alternatives (MGA) formalized near-optimal as the region comprising the original problem constraints plus a new constraint that allowed performance within a specified tolerance of the optimal objective function value. MGA identified a few maximally-different alternatives from the near-optimal region. Subsequent work applied Markov Chain Monte Carlo (MCMC) sampling to generate a larger number of alternatives that span the near-optimal region of linear problems or select portions for non-linear problems. We extend the MCMC Hit-And-Run method to generate alternatives that span the full extent of the near-optimal region for non-linear, non-convex problems. First, start at a feasible hit point within the near-optimal region, then run a random distance in a random direction to a new hit point. Next, repeat until generating the desired number of alternatives. The key step at each iterate is to run a random distance along the line in the specified direction to a new hit point. If linear equity constraints exist, we construct an orthogonal basis and use a null space transformation to confine hits and runs to a lower-dimensional space. Linear inequity constraints define the convex bounds on the line that runs through the current hit point in the specified direction. We then use slice sampling to identify a new hit point along the line within bounds defined by the non-linear inequity constraints. This technique is computationally efficient compared to prior near-optimal alternative generation techniques such MGA, MCMC Metropolis-Hastings, evolutionary, or firefly algorithms because search at each iteration is confined to the hit line, the algorithm can move in one step to any point in the near-optimal region, and each iterate generates a new, feasible alternative. We use the method to generate alternatives that span the near-optimal regions of simple and more complicated water management problems and may be preferred to optimal solutions. We also discuss extensions to handle non-linear equity constraints.

From Usability Testing to Clinical Simulations: Bringing Context into the Design and Evaluation of Usable and Safe Health Information Technologies. Contribution of the IMIA Human Factors Engineering for Healthcare Informatics Working Group.

PubMed

Kushniruk, A; Nohr, C; Jensen, S; Borycki, E M

2013-01-01

The objective of this paper is to explore human factors approaches to understanding the use of health information technology (HIT) by extending usability engineering approaches to include analysis of the impact of clinical context through use of clinical simulations. Methods discussed are considered on a continuum from traditional laboratory-based usability testing to clinical simulations. Clinical simulations can be conducted in a simulation laboratory and they can also be conducted in real-world settings. The clinical simulation approach attempts to bring the dimension of clinical context into stronger focus. This involves testing of systems with representative users doing representative tasks, in representative settings/environments. Application of methods where realistic clinical scenarios are used to drive the study of users interacting with systems under realistic conditions and settings can lead to identification of problems and issues with systems that may not be detected using traditional usability engineering methods. In conducting such studies, careful consideration is needed in creating ecologically valid test scenarios. The evidence obtained from such evaluation can be used to improve both the usability and safety of HIT. In addition, recent work has shown that clinical simulations, in particular those conducted in-situ, can lead to considerable benefits when compared to the costs of running such studies. In order to bring context of use into the testing of HIT, clinical simulation, involving observing representative users carrying out tasks in representative settings, holds considerable promise.

Development and psychometric evaluation of the Impact of Health Information Technology (I-HIT) scale.

PubMed

Dykes, Patricia C; Hurley, Ann; Cashen, Margaret; Bakken, Suzanne; Duffy, Mary E

2007-01-01

The use of health information technology (HIT) for the support of communication processes and data and information access in acute care settings is a relatively new phenomenon. A means of evaluating the impact of HIT in hospital settings is needed. The purpose of this research was to design and psychometrically evaluate the Impact of Health Information Technology scale (I-HIT). I-HIT was designed to measure the perception of nurses regarding the ways in which HIT influences interdisciplinary communication and workflow patterns and nurses' satisfaction with HIT applications and tools. Content for a 43-item tool was derived from the literature, and supported theoretically by the Coiera model and by nurse informaticists. Internal consistency reliability analysis using Cronbach's alpha was conducted on the 43-item scale to initiate the item reduction process. Items with an item total correlation of less than 0.35 were removed, leaving a total of 29 items. Item analysis, exploratory principal component analysis and internal consistency reliability using Cronbach's alpha were used to confirm the 29-item scale. Principal components analysis with Varimax rotation produced a four-factor solution that explained 58.5% of total variance (general advantages, information tools to support information needs, information tools to support communication needs, and workflow implications). Internal consistency of the total scale was 0.95 and ranged from 0.80-0.89 for four subscales. I-HIT demonstrated psychometric adequacy and is recommended to measure the impact of HIT on nursing practice in acute care settings.

Enhancing the chemical selectivity in discovery-based analysis with tandem ionization time-of-flight mass spectrometry detection for comprehensive two-dimensional gas chromatography.

PubMed

Freye, Chris E; Moore, Nicholas R; Synovec, Robert E

2018-02-16

The complementary information provided by tandem ionization time-of-flight mass spectrometry (TI-TOFMS) is investigated for comparative discovery-based analysis, when coupled with comprehensive two-dimensional gas chromatography (GC × GC). The TI conditions implemented were a hard ionization energy (70 eV) concurrently collected with a soft ionization energy (14 eV). Tile-based Fisher ratio (F-ratio) analysis is used to analyze diesel fuel spiked with twelve analytes at a nominal concentration of 50 ppm. F-ratio analysis is a supervised discovery-based technique that compares two different sample classes, in this case spiked and unspiked diesel, to reduce the complex GC × GC-TI-TOFMS data into a hit list of class distinguishing analyte features. Hit lists of the 70 eV and 14 eV data sets, and the single hit list produced when the two data sets are fused together, are all investigated. For the 70 eV hit list, eleven of the twelve analytes were found in the top thirteen hits. For the 14 eV hit list, nine of the twelve analytes were found in the top nine hits, with the other three analytes either not found or well down the hit list. As expected, the F-ratios per m/z used to calculate each average F-ratio per hit were generally smaller fragment ions for the 70 eV data set, while the larger fragment ions were emphasized in the 14 eV data set, supporting the notion that complementary information was provided. The discovery rate was improved when F-ratio analysis was performed on the fused data sets resulted in eleven of the twelve analytes being at the top of the single hit list. Using PARAFAC, analytes that were "discovered" were deconvoluted in order to obtain their identification via match values (MV). Location of the analytes and the "F-ratio spectra" obtained from F-ratio analysis were used to guide the deconvolution. Eight of the twelve analytes where successfully deconvoluted and identified using the in-house library for the 70 eV data set. PARAFAC deconvolution of the two separate data sets provided increased confidence in identification of "discovered" analytes. Herein, we explore the limit of analyte discovery and limit of analyte identification, and demonstrate a general workflow for the investigation of key chemical features in complex samples. Copyright © 2018 Elsevier B.V. All rights reserved.

Straightforward hit identification approach in fragment-based discovery of bromodomain-containing protein 4 (BRD4) inhibitors.

PubMed

Borysko, Petro; Moroz, Yurii S; Vasylchenko, Oleksandr V; Hurmach, Vasyl V; Starodubtseva, Anastasia; Stefanishena, Natalia; Nesteruk, Kateryna; Zozulya, Sergey; Kondratov, Ivan S; Grygorenko, Oleksandr O

2018-05-09

A combination approach of a fragment screening and "SAR by catalog" was used for the discovery of bromodomain-containing protein 4 (BRD4) inhibitors. Initial screening of 3695-fragment library against bromodomain 1 of BRD4 using thermal shift assay (TSA), followed by initial hit validation, resulted in 73 fragment hits, which were used to construct a follow-up library selected from available screening collection. Additionally, analogs of inactive fragments, as well as a set of randomly selected compounds were also prepared (3 × 3200 compounds in total). Screening of the resulting sets using TSA, followed by re-testing at several concentrations, counter-screen, and TR-FRET assay resulted in 18 confirmed hits. Compounds derived from the initial fragment set showed better hit rate as compared to the other two sets. Finally, building dose-response curves revealed three compounds with IC 50  = 1.9-7.4 μM. For these compounds, binding sites and conformations in the BRD4 (4UYD) have been determined by docking. Copyright © 2018 Elsevier Ltd. All rights reserved.

NIMROD Modeling of HIT-SI and HIT-SI3

NASA Astrophysics Data System (ADS)

Morgan, Kyle; Jarboe, Tom; Hossack, Aaron

2016-10-01

The HIT-SI and HIT-SI3 devices are spheromaks formed and sustained via a set of Steady Inductive Helicity Injectors (SIHI) that are operated in AC. The experiment explores the formation and sustain of stable spheromaks with a variety of perturbation mode structures. The HIT-SI device consisted of two injectors with primarily n = 1 toroidal symmetry while the HIT-SI3 device has three injectors capable of a mixture of n = 1 and n = 2 perturbations or a primarily n = 3 perturbation, depending on the relative phase of the injectors. Using the NIMROD code to model these devices, we are able to validate with experimental results (previously only done on HIT-SI) and examine the interaction between the injectors and the spheromak. Simulations are performed with both finite and zero- β models to gain an understanding of the thermal properties of the device. Additionally, a set of extrapolation simulations has been performed illustrating the spontaneous formation of closed flux surfaces at high current amplification. Work supported by the US DOE.

Obstacles in the diagnostics and therapy of heparin-induced thrombocytopenia.

PubMed

Antonijević, Nebojsa M; Radovanović, Nebojsa; Obradović, Slobodan; Vucelić, Dragica; Stojanović, Bojan; Miković, Danijela; Kovac, Mirjana; Kocica, Tina; Tadić, Svetlana; Antonijević, Irina; Drasković, Snezana; Djordjević, Valentina; Calija, Branko; Perunicić, Jovan; Vasiljević, Zorana

2010-01-01

An immune-mediated, severe, acquired prothrombotic disorder, heparin-induced thrombocytopenia type II (HIT II) occurs in 0.5-5% of patients exposed to unfractionated heparin longer than 5-7 days. Arterial and venous thromboses are induced by HIT II in about 35-50% of patients. Typical death rate for HIT is about 29%, while 21% of HIT patients result in amputation of a limb. The trend towards the occurrence of HIT due to the administration of low molecular weight heparins (LMWH) taking ever conspicuous place in the standard venous thromboembolism (VTE) prophylaxis has been more frequently observed recently. It is considered that LMWH may cause HIT II in about 0.25-1%. The need for further modification of HIPA assays with LMWH has been imposed in the HIT laboratory diagnostics, heretofore overburdened with complexity. There are several constantly opposing problems arising in HIT laboratory diagnostics, one of which is that in a certain number of patients immunologic assays detect nonpathogenic antibodies (mainly IgM or IgA heparin-PF4 antibodies) while, on the other hand, the occurrence of HIT pathogenetically mediated by minor antigens (neutrophil-activating peptide 2 or interleukin 8) may be neglected in certain cases. The following factors play an important role in the interpretation of each laboratory HIT assays performed: 1. correlation with HIT clinical probability test, the best known of which is 4T'score, 2. the interpretation of the laboratory findings dependent on the time of the thrombocytopenia onset, as well as 3. the sensitivity and specificity of each test respectively. The HIT diagnostics in the presence of other comorbid states which may also induce thrombocytopenia, more precisely known as pseudo HIT (cancer, sepsis, disseminated intravascular coagulation, pulmonary embolism, antiphospholipid syndrome, etc), represents a specific clinical problem.

vSDC: a method to improve early recognition in virtual screening when limited experimental resources are available.

PubMed

Chaput, Ludovic; Martinez-Sanz, Juan; Quiniou, Eric; Rigolet, Pascal; Saettel, Nicolas; Mouawad, Liliane

2016-01-01

In drug design, one may be confronted to the problem of finding hits for targets for which no small inhibiting molecules are known and only low-throughput experiments are available (like ITC or NMR studies), two common difficulties encountered in a typical academic setting. Using a virtual screening strategy like docking can alleviate some of the problems and save a considerable amount of time by selecting only top-ranking molecules, but only if the method is very efficient, i.e. when a good proportion of actives are found in the 1-10 % best ranked molecules. The use of several programs (in our study, Gold, Surflex, FlexX and Glide were considered) shows a divergence of the results, which presents a difficulty in guiding the experiments. To overcome this divergence and increase the yield of the virtual screening, we created the standard deviation consensus (SDC) and variable SDC (vSDC) methods, consisting of the intersection of molecule sets from several virtual screening programs, based on the standard deviations of their ranking distributions. SDC allowed us to find hits for two new protein targets by testing only 9 and 11 small molecules from a chemical library of circa 15,000 compounds. Furthermore, vSDC, when applied to the 102 proteins of the DUD-E benchmarking database, succeeded in finding more hits than any of the four isolated programs for 13-60 % of the targets. In addition, when only 10 molecules of each of the 102 chemical libraries were considered, vSDC performed better in the number of hits found, with an improvement of 6-24 % over the 10 best-ranked molecules given by the individual docking programs.Graphical abstractIn drug design, for a given target and a given chemical library, the results obtained with different virtual screening programs are divergent. So how to rationally guide the experimental tests, especially when only a few number of experiments can be made? The variable Standard Deviation Consensus (vSDC) method was developed to answer this issue. Left panel the vSDC principle consists of intersecting molecule sets, chosen on the basis of the standard deviations of their ranking distributions, obtained from various virtual screening programs. In this study Glide, Gold, FlexX and Surflex were used and tested on the 102 targets of the DUD-E database. Right panel Comparison of the average percentage of hits found with vSDC and each of the four programs, when only 10 molecules from each of the 102 chemical libraries of the DUD-E database were considered. On average, vSDC was capable of finding 38 % of the findable hits, against 34 % for Glide, 32 % for Gold, 16 % for FlexX and 14 % for Surflex, showing that with vSDC, it was possible to overcome the unpredictability of the virtual screening results and to improve them.

Low-Volume High-Intensity Interval Training in a Gym Setting Improves Cardio-Metabolic and Psychological Health.

PubMed

Shepherd, Sam O; Wilson, Oliver J; Taylor, Alexandra S; Thøgersen-Ntoumani, Cecilie; Adlan, Ahmed M; Wagenmakers, Anton J M; Shaw, Christopher S

2015-01-01

Within a controlled laboratory environment, high-intensity interval training (HIT) elicits similar cardiovascular and metabolic benefits as traditional moderate-intensity continuous training (MICT). It is currently unclear how HIT can be applied effectively in a real-world environment. To investigate the hypothesis that 10 weeks of HIT, performed in an instructor-led, group-based gym setting, elicits improvements in aerobic capacity (VO2max), cardio-metabolic risk and psychological health which are comparable to MICT. Ninety physically inactive volunteers (42±11 y, 27.7±4.8 kg.m-2) were randomly assigned to HIT or MICT group exercise classes. HIT consisted of repeated sprints (15-60 seconds, >90% HRmax) interspersed with periods of recovery cycling (≤25 min.session-1, 3 sessions.week-1). MICT participants performed continuous cycling (~70% HRmax, 30-45 min.session-1, 5 sessions.week-1). VO2max, markers of cardio-metabolic risk, and psychological health were assessed pre and post-intervention. Mean weekly training time was 55±10 (HIT) and 128±44 min (MICT) (p<0.05), with greater adherence to HIT (83±14% vs. 61±15% prescribed sessions attended, respectively; p<0.05). HIT improved VO2max, insulin sensitivity, reduced abdominal fat mass, and induced favourable changes in blood lipids (p<0.05). HIT also induced beneficial effects on health perceptions, positive and negative affect, and subjective vitality (p<0.05). No difference between HIT and MICT was seen for any of these variables. HIT performed in a real-world gym setting improves cardio-metabolic risk factors and psychological health in physically inactive adults. With a reduced time commitment and greater adherence than MICT, HIT offers a viable and effective exercise strategy to target the growing incidence of metabolic disease and psychological ill-being associated with physical inactivity.

Low-Volume High-Intensity Interval Training in a Gym Setting Improves Cardio-Metabolic and Psychological Health

PubMed Central

Shepherd, Sam O.; Wilson, Oliver J.; Taylor, Alexandra S.; Thøgersen-Ntoumani, Cecilie; Adlan, Ahmed M.; Wagenmakers, Anton J. M.; Shaw, Christopher S.

2015-01-01

Background Within a controlled laboratory environment, high-intensity interval training (HIT) elicits similar cardiovascular and metabolic benefits as traditional moderate-intensity continuous training (MICT). It is currently unclear how HIT can be applied effectively in a real-world environment. Purpose To investigate the hypothesis that 10 weeks of HIT, performed in an instructor-led, group-based gym setting, elicits improvements in aerobic capacity (VO2max), cardio-metabolic risk and psychological health which are comparable to MICT. Methods Ninety physically inactive volunteers (42±11 y, 27.7±4.8 kg.m-2) were randomly assigned to HIT or MICT group exercise classes. HIT consisted of repeated sprints (15–60 seconds, >90% HRmax) interspersed with periods of recovery cycling (≤25 min.session-1, 3 sessions.week-1). MICT participants performed continuous cycling (~70% HRmax, 30–45 min.session-1, 5 sessions.week-1). VO2max, markers of cardio-metabolic risk, and psychological health were assessed pre and post-intervention. Results Mean weekly training time was 55±10 (HIT) and 128±44 min (MICT) (p<0.05), with greater adherence to HIT (83±14% vs. 61±15% prescribed sessions attended, respectively; p<0.05). HIT improved VO2max, insulin sensitivity, reduced abdominal fat mass, and induced favourable changes in blood lipids (p<0.05). HIT also induced beneficial effects on health perceptions, positive and negative affect, and subjective vitality (p<0.05). No difference between HIT and MICT was seen for any of these variables. Conclusions HIT performed in a real-world gym setting improves cardio-metabolic risk factors and psychological health in physically inactive adults. With a reduced time commitment and greater adherence than MICT, HIT offers a viable and effective exercise strategy to target the growing incidence of metabolic disease and psychological ill-being associated with physical inactivity. PMID:26402859

Predictors of Osteopathic Medical Students' Readiness to Use Health Information Technology.

PubMed

Jacobs, Robin J; Iqbal, Hassan; Rana, Arif M; Rana, Zaid; Kane, Michael N

2017-12-01

The advent of health information technology (HIT) tools can affect the practice of modern medicine in many ways, ideally by improving quality of care and efficiency and reducing medical errors. Future physicians will play a key role in the successful implementation of HIT. However, osteopathic medical students' willingness to learn, adopt, and use technology in a health care setting is not well understood. To understand osteopathic medical students' knowledge, attitudes, and behaviors regarding HIT and to identify factors that may be related to their readiness to use HIT. Using a cross-sectional approach, quantitative surveys were collected from students attending a large osteopathic medical school. Multivariate regression modeling was used to determine whether knowledge, attitudes, behaviors, and personal characteristics were associated with students' readiness to use HIT in future clinical practice. Six hundred four students responded to at least 70% of the survey and were included in the analysis. Multivariate modeling successfully explained the 26% of variance in predicting students' readiness to use HIT (F8,506=22.6, P<.001, R2=0.263). Greater self-efficacy, openness to change (in academic/work settings), favorable attitudes toward HIT use, mobile technology use, younger age, being male, and prior exposure to technology were associated with readiness to use HIT. Understanding students' level of HIT readiness may help guide medical education intervention efforts to better prepare future osteopathic physicians for HIT engagement and use. Innovative approaches to HIT education in medical school curricula that include biomedical informatics may be necessary.

HIT and brain reward function: A case of mistaken identity (theory).

PubMed

Wright, Cory; Colombo, Matteo; Beard, Alexander

2017-08-01

This paper employs a case study from the history of neuroscience-brain reward function-to scrutinize the inductive argument for the so-called 'Heuristic Identity Theory' (HIT). The case fails to support HIT, illustrating why other case studies previously thought to provide empirical support for HIT also fold under scrutiny. After distinguishing two different ways of understanding the types of identity claims presupposed by HIT and considering other conceptual problems, we conclude that HIT is not an alternative to the traditional identity theory so much as a relabeling of previously discussed strategies for mechanistic discovery. Copyright © 2017. Published by Elsevier Ltd.

Dual hit lipopolysaccharide & oleic acid combination induced rat model of acute lung injury/acute respiratory distress syndrome.

PubMed

Hagawane, T N; Gaikwad, R V; Kshirsagar, N A

2016-05-01

Despite advances in therapy and overall medical care, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) management remains a problem. Hence the objective of this study was to develop a rat model that mimics human ALI/ARDS. Four groups of Wistar rats, 48 per group were treated with (i) intratracheal (IT) lipopolysaccharide (LPS) (5 mg/kg) dissolved in normal saline (NS), (ii) intravenous (iv) oleic acid (OA) (250 μl/kg) suspension in bovine serum albumin (BSA), (iii) dual hit: IT LPS (2 mg/kg) dissolved in NS and iv OA (100 μl/kg) and (iv) control group: IT NS and iv BSA. From each group at set periods of time various investigations like chest x-rays, respiratory rate (RR), tidal volume (TV), total cell count, differential cell count, total protein count and cytokine levels in bronchoalveolar lavage fluid (BALF), lung wet/dry weight ratio and histopathological examination were done. It was noted that the respiratory rate, and tumour necrosis factor-α (TNF-α) levels were significantly higher at 4 h in the dual hit group as compared to LPS, OA and control groups. Interleukin-6 (IL-6) levels were significantly higher in the dual hit group as compared to LPS at 8 and 24 h, OA at 8 h and control (at all time intervals) group. IL-1β levels were significantly higher in LPS and dual hit groups at all time intervals, but not in OA and control groups. The injury induced in dual hit group was earlier and more sustained as compared to LPS and OA alone. The lung pathology and changes in respiration functions produced by the dual hit model were closer to the diagnostic criteria of ALI/ARDS in terms of clinical manifestations and pulmonary injury and the injury persisted longer as compared to LPS and OA single hit model. Therefore, the ARDS model produced by the dual hit method was closer to the diagnostic criteria of ARDS in terms of clinical manifestations and pulmonary injury.

Designing Patient-facing Health Information Technologies for the Outpatient Settings: A Literature Review.

PubMed

Yang, Yushi; Asan, Onur

2016-04-06

  The implementation of health information technologies (HITs) has changed the dynamics of doctor-patient communication in outpatient settings. Designing patient-facing HITs provides patients with easy access to healthcare information during the visit and has the potential to enhance the patient-centred care.  The objectives of this study are to systematically review how the designs of patient-facing HITs have been suggested and evaluated, and how they may potentially affect the doctor-patient communication and patient-centred care.  We conducted an online database search to identify articles published before December 2014 relevant to the objectives of this study. A total of nine papers have been identified and reviewed in this study.  Designing patient-facing HITs is at an early stage. The current literature has been exploring the impact of HITs on doctor-patient communication dynamics. Based on the findings of these studies, there is an emergent need to design more patient-centred HITs. There are also some papers that focus on the usability evaluation of some preliminary prototypes of the patient-facing HITs. The design styles of patient-facing HITs included sharing the health information with the patients on: (1) a separate patient display, (2) a projector, (3) a portable tablet, (4) a touch-based screen and (5) a shared computer display that can be viewed by both doctors and patients. Each of them had the strengths and limitations to facilitate the patient-centred care, and it is worthwhile to make a comparison of them in order to identify future research directions.  The designs of patient-facing HITs in outpatient settings are promising in facilitating the doctor-patient communication and patient engagement. However, their effectiveness and usefulness need to be further evaluated and improved from a systems perspective.

Design and implementation of a hospital-based usability laboratory: insights from a Department of Veterans Affairs laboratory for health information technology.

PubMed

Russ, Alissa L; Weiner, Michael; Russell, Scott A; Baker, Darrell A; Fahner, W Jeffrey; Saleem, Jason J

2012-12-01

Although the potential benefits of more usable health information technologies (HIT) are substantial-reduced HIT support costs, increased work efficiency, and improved patient safety--human factors methods to improve usability are rarely employed. The US Department of Veterans Affairs (VA) has emerged as an early leader in establishing usability laboratories to inform the design of HIT, including its electronic health record. Experience with a usability laboratory at a VA Medical Center provides insights on how to design, implement, and leverage usability laboratories in the health care setting. The VA Health Services Research and Development Service Human-Computer Interaction & Simulation Laboratory emerged as one of the first VA usability laboratories and was intended to provide research-based findings about HIT designs. This laboratory supports rapid prototyping, formal usability testing, and analysis tools to assess existing technologies, alternative designs, and potential future technologies. RESULTS OF IMPLEMENTATION: Although the laboratory has maintained a research focus, it has become increasingly integrated with VA operations, both within the medical center and on a national VA level. With this resource, data-driven recommendations have been provided for the design of HIT applications before and after implementation. The demand for usability testing of HIT is increasing, and information on how to develop usability laboratories for the health care setting is often needed. This article may assist other health care organizations that want to invest in usability resources to improve HIT. The establishment and utilization of usability laboratories in the health care setting may improve HIT designs and promote safe, high-quality care for patients.

CHRR: coordinate hit-and-run with rounding for uniform sampling of constraint-based models

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

Haraldsdóttir, Hulda S.; Cousins, Ben; Thiele, Ines

In constraint-based metabolic modelling, physical and biochemical constraints define a polyhedral convex set of feasible flux vectors. Uniform sampling of this set provides an unbiased characterization of the metabolic capabilities of a biochemical network. However, reliable uniform sampling of genome-scale biochemical networks is challenging due to their high dimensionality and inherent anisotropy. Here, we present an implementation of a new sampling algorithm, coordinate hit-and-run with rounding (CHRR). This algorithm is based on the provably efficient hit-and-run random walk and crucially uses a preprocessing step to round the anisotropic flux set. CHRR provably converges to a uniform stationary sampling distribution. Wemore » apply it to metabolic networks of increasing dimensionality. We show that it converges several times faster than a popular artificial centering hit-and-run algorithm, enabling reliable and tractable sampling of genome-scale biochemical networks.« less

CHRR: coordinate hit-and-run with rounding for uniform sampling of constraint-based models

DOE PAGES

Haraldsdóttir, Hulda S.; Cousins, Ben; Thiele, Ines; ...

2017-01-31

In constraint-based metabolic modelling, physical and biochemical constraints define a polyhedral convex set of feasible flux vectors. Uniform sampling of this set provides an unbiased characterization of the metabolic capabilities of a biochemical network. However, reliable uniform sampling of genome-scale biochemical networks is challenging due to their high dimensionality and inherent anisotropy. Here, we present an implementation of a new sampling algorithm, coordinate hit-and-run with rounding (CHRR). This algorithm is based on the provably efficient hit-and-run random walk and crucially uses a preprocessing step to round the anisotropic flux set. CHRR provably converges to a uniform stationary sampling distribution. Wemore » apply it to metabolic networks of increasing dimensionality. We show that it converges several times faster than a popular artificial centering hit-and-run algorithm, enabling reliable and tractable sampling of genome-scale biochemical networks.« less

The impact of Health Information Technology (I-HIT) Scale: the Australian results.

PubMed

Cook, Robyn; Foster, Joanne

2009-01-01

One of role of the nurse in the clinical setting is that of co-ordinating communication across the healthcare team. On a daily basis nurses interact with the person receiving care, their family members, and multiple care providers thus placing the nurse in the central position with access to a vast array of information on the person. Through this nurses have historically functioned as "information repositories". With the advent of Health Information Technology (HIT) tools there is a potential that HIT could impact interdisciplinary communication, practice efficiency and effectiveness, relationships and workflow in acute care settings [1][3]. In 2005, the HIMSS Nursing Informatics Community developed the I-HIT Scale to measure the impact of HIT on the nursing role and interdisciplinary communication in USA hospitals. In 2007, nursing informatics colleagues from Australia, Finland, Ireland, New Zealand, Scotland and the USA formed a research collaborative to validate the I-HIT in six additional countries. This paper will discuss the background, methodology, results and implications from the Australian I-HIT survey of over 1,100 nurses. The results are currently being analyzed and will be presented at the conference.

Studying the HIT-Complexity Interchange.

PubMed

Kuziemsky, Craig E; Borycki, Elizabeth M; Kushniruk, Andre W

2016-01-01

The design and implementation of health information technology (HIT) is challenging, particularly when it is being introduced into complex settings. While complex adaptive system (CASs) can be a valuable means of understanding relationships between users, HIT and tasks, much of the existing work using CASs is descriptive in nature. This paper addresses that issue by integrating a model for analyzing task complexity with approaches for HIT evaluation and systems analysis. The resulting framework classifies HIT-user tasks and issues as simple, complicated or complex, and provides insight on how to study them.

Health information technology knowledge and skills needed by HIT employers.

PubMed

Fenton, S H; Gongora-Ferraez, M J; Joost, E

2012-01-01

To evaluate the health information technology (HIT) workforce knowledge and skills needed by HIT employers. Statewide face-to-face and online focus groups of identified HIT employer groups in Austin, Brownsville, College Station, Dallas, El Paso, Houston, Lubbock, San Antonio, and webinars for rural health and nursing informatics. HIT employers reported needing an HIT workforce with diverse knowledge and skills ranging from basic to advanced, while covering information technology, privacy and security, clinical practice, needs assessment, contract negotiation, and many other areas. Consistent themes were that employees needed to be able to learn on the job and must possess the ability to think critically and problem solve. Many employers wanted persons with technical skills, yet also the knowledge and understanding of healthcare operations. The HIT employer focus groups provided valuable insight into employee skills needed in this fast-growing field. Additionally, this information will be utilized to develop a statewide HIT workforce needs assessment survey.

Are We There Yet? Human Factors Knowledge and Health Information Technology - the Challenges of Implementation and Impact.

PubMed

Turner, P; Kushniruk, A; Nohr, C

2017-08-01

Objective: To review the developments in human factors (HF) research on the challenges of health information technology (HIT) implementation and impact given the continuing incidence of usability problems and unintended consequences from HIT development and use. Methods: A search of PubMed/Medline and Web of Science® identified HF research published in 2015 and 2016. Electronic health records (EHRs) and patient-centred HIT emerged as significant foci of recent HF research. The authors selected prominent papers highlighting ongoing HF and usability challenges in these areas. This selective rather than systematic review of recent HF research highlights these key challenges and reflects on their implications on the future impact of HF research on HIT. Results: Research provides evidence of continued poor design, implementation, and usability of HIT, as well as technology-induced errors and unintended consequences. The paper highlights support for: (i) strengthening the evidence base on the benefits of HF approaches; (ii) improving knowledge translation in the implementation of HF approaches during HIT design, implementation, and evaluation; (iii) increasing transparency, governance, and enforcement of HF best practices at all stages of the HIT system development life cycle. Discussion and Conclusion: HF and usability approaches are yet to become embedded as integral components of HIT development, implementation, and impact assessment. As HIT becomes ever-more pervasive including with patients as end-users, there is a need to expand our conceptualisation of the problems to be addressed and the suite of tactics and strategies to be used to calibrate our pro-active involvement in its improvement. Georg Thieme Verlag KG Stuttgart.

Argatroban for an alternative anticoagulant in HIT during ECMO.

PubMed

Rougé, Alain; Pelen, Felix; Durand, Michel; Schwebel, Carole

2017-01-01

Extracorporeal membrane oxygenation (ECMO) have become more frequently used in daily ICU practice, heparin-induced thrombocytopenia (HIT) is a rare but life-threatening complication while on extracorporeal membrane oxygenation (ECMO). HIT confirmation directly impacts on anticoagulant strategy requiring no delay unfractionated heparin discontinuation to be replaced by alternative systemic anticoagulant treatment. We report two clinical cases of HIT occurring during ECMO in various settings with subsequent recovery with argatroban and provide literature review to help physicians treat HIT during ECMO in clinical daily practice. HIT during ECMO is uncommon, and despite the absence of recommendation, argatroban seems to be an appropriate and safe therapeutic option. Finally, there are not enough arguments favouring routine circuit change in the event of HIT during ECMO.

The lattice Boltzmann method and the problem of turbulence

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

Djenidi, L.

2015-03-10

This paper reports a brief review of numerical simulations of homogeneous isotopic turbulence (HIT) using the lattice Boltzmann method (LBM). The LBM results shows that the details of HIT are well captured and in agreement with existing data. This clearly indicates that the LBM is as good as current Navier-Stokes solvers and is very much adequate for investigating the problem of turbulence.

Universal Hitting Time Statistics for Integrable Flows

NASA Astrophysics Data System (ADS)

Dettmann, Carl P.; Marklof, Jens; Strömbergsson, Andreas

2017-02-01

The perceived randomness in the time evolution of "chaotic" dynamical systems can be characterized by universal probabilistic limit laws, which do not depend on the fine features of the individual system. One important example is the Poisson law for the times at which a particle with random initial data hits a small set. This was proved in various settings for dynamical systems with strong mixing properties. The key result of the present study is that, despite the absence of mixing, the hitting times of integrable flows also satisfy universal limit laws which are, however, not Poisson. We describe the limit distributions for "generic" integrable flows and a natural class of target sets, and illustrate our findings with two examples: the dynamics in central force fields and ellipse billiards. The convergence of the hitting time process follows from a new equidistribution theorem in the space of lattices, which is of independent interest. Its proof exploits Ratner's measure classification theorem for unipotent flows, and extends earlier work of Elkies and McMullen.

A framework for reporting on human factor/usability studies of health information technologies.

PubMed

Peute, Linda W; Driest, Keiko F; Marcilly, Romaric; Bras Da Costa, Sabrina; Beuscart-Zephir, Marie-Catherine; Jaspers, Monique W M

2013-01-01

Increasingly, studies are being published on the potential negative effect of introducing poor designed Health Information Technology (HIT) into clinical settings, relating to technology-induced errors and adverse events. Academic research on HIT design and evaluation is an extremely important source of information in providing new insights into factors contributing to successful system (re)design efforts, system user-friendliness and usability issues and safety critical aspects of HIT design. However, these studies have been inconsistent and incomprehensive in their reporting, complicating the appraisal of outcomes, generalizability of study findings, meta-analysis and harmonization of the available evidence. To improve identification of type of use errors and safety related issues regarding design and implementation of HIT, consensus on issues to be reported on in scientific publications is a necessary step forward. This study presents the first approach to a framework providing a set of principles to follow for comprehensive and unambiguous reporting of HIT design and usability evaluation studies with the objective to reduce variation, improve on the publication reporting quality and proper indexation of these studies. This framework may be helpful in expanding the knowledge base not only concerning the application of Human Factors (HF)/Usability studies of HIT but also improve the knowledge base of how to (re)design and implement effective, efficient and safe HIT.

Health Information Technology Knowledge and Skills Needed by HIT Employers

PubMed Central

Fenton, S.H.; Gongora-Ferraez, M.J.; Joost, E.

2012-01-01

Objective To evaluate the health information technology (HIT) workforce knowledge and skills needed by HIT employers. Methods Statewide face-to-face and online focus groups of identified HIT employer groups in Austin, Brownsville, College Station, Dallas, El Paso, Houston, Lubbock, San Antonio, and webinars for rural health and nursing informatics. Results HIT employers reported needing an HIT workforce with diverse knowledge and skills ranging from basic to advanced, while covering information technology, privacy and security, clinical practice, needs assessment, contract negotiation, and many other areas. Consistent themes were that employees needed to be able to learn on the job and must possess the ability to think critically and problem solve. Many employers wanted persons with technical skills, yet also the knowledge and understanding of healthcare operations. Conclusion The HIT employer focus groups provided valuable insight into employee skills needed in this fast-growing field. Additionally, this information will be utilized to develop a statewide HIT workforce needs assessment survey. PMID:23646090

Designing small universal k-mer hitting sets for improved analysis of high-throughput sequencing

PubMed Central

Kingsford, Carl

2017-01-01

With the rapidly increasing volume of deep sequencing data, more efficient algorithms and data structures are needed. Minimizers are a central recent paradigm that has improved various sequence analysis tasks, including hashing for faster read overlap detection, sparse suffix arrays for creating smaller indexes, and Bloom filters for speeding up sequence search. Here, we propose an alternative paradigm that can lead to substantial further improvement in these and other tasks. For integers k and L > k, we say that a set of k-mers is a universal hitting set (UHS) if every possible L-long sequence must contain a k-mer from the set. We develop a heuristic called DOCKS to find a compact UHS, which works in two phases: The first phase is solved optimally, and for the second we propose several efficient heuristics, trading set size for speed and memory. The use of heuristics is motivated by showing the NP-hardness of a closely related problem. We show that DOCKS works well in practice and produces UHSs that are very close to a theoretical lower bound. We present results for various values of k and L and by applying them to real genomes show that UHSs indeed improve over minimizers. In particular, DOCKS uses less than 30% of the 10-mers needed to span the human genome compared to minimizers. The software and computed UHSs are freely available at github.com/Shamir-Lab/DOCKS/ and acgt.cs.tau.ac.il/docks/, respectively. PMID:28968408

Validation of the Impact of Health Information Technology (I-HIT) Scale: an international collaborative.

PubMed

Dykes, Patricia C; Hurley, Ann C; Brown, Suzanne; Carr, Robyn; Cashen, Margaret; Collins, Rita; Cook, Robyn; Currie, Leanne; Docherty, Charles; Ensio, Anneli; Foster, Joanne; Hardiker, Nicholas R; Honey, Michelle L L; Killalea, Rosaleen; Murphy, Judy; Saranto, Kaija; Sensmeier, Joyce; Weaver, Charlotte

2009-01-01

In 2005, the Healthcare Information Management Systems Society (HIMSS) Nursing Informatics Community developed a survey to measure the impact of health information technology (HIT), the I-HIT Scale, on the role of nurses and interdisciplinary communication in hospital settings. In 2007, nursing informatics colleagues from Australia, England, Finland, Ireland, New Zealand, Scotland and the United States formed a research collaborative to validate the I-HIT across countries. All teams have completed construct and face validation in their countries. Five out of six teams have initiated reliability testing by practicing nurses. This paper reports the international collaborative's validation of the I-HIT Scale completed to date.

Exploring interpersonal behavior and team sensemaking during health information technology implementation.

PubMed

Kitzmiller, Rebecca R; McDaniel, Reuben R; Johnson, Constance M; Lind, E Allan; Anderson, Ruth A

2013-01-01

We examine how interpersonal behavior and social interaction influence team sensemaking and subsequent team actions during a hospital-based health information technology (HIT) implementation project. Over the course of 18 months, we directly observed the interpersonal interactions of HIT implementation teams using a sensemaking lens. We identified three voice-promoting strategies enacted by team leaders that fostered team member voice and sensemaking; communicating a vision; connecting goals to team member values; and seeking team member input. However, infrequent leader expressions of anger quickly undermined team sensemaking, halting dialog essential to problem solving. By seeking team member opinions, team leaders overcame the negative effects of anger. Leaders must enact voice-promoting behaviors and use them throughout a team's engagement. Further, training teams in how to use conflict to achieve greater innovation may improve sensemaking essential to project risk mitigation. Health care work processes are complex; teams involved in implementing improvements must be prepared to deal with conflicting, contentious issues, which will arise during change. Therefore, team conflict training may be essential to sustaining sensemaking. Future research should seek to identify team interactions that foster sensemaking, especially when topics are difficult or unwelcome, then determine the association between staff sensemaking and the impact on HIT implementation outcomes. We are among the first to focus on project teams tasked with HIT implementation. This research extends our understanding of how leaders' behaviors might facilitate or impeded speaking up among project teams in health care settings.

Design of the rivaroxaban for heparin-induced thrombocytopenia study.

PubMed

Linkins, Lori-Ann; Warkentin, Theodore E; Pai, Menaka; Shivakumar, Sudeep; Manji, Rizwan A; Wells, Philip S; Crowther, Mark A

2014-11-01

Rivaroxaban is an ideal potential candidate for treatment of heparin-induced thrombocytopenia (HIT) because it is administered orally by fixed dosing, requires no laboratory monitoring and is effective in the treatment of venous and arterial thromboembolism in other settings. The Rivaroxaban for HIT study is a prospective, multicentre, single-arm, cohort study evaluating the incidence of new symptomatic venous and arterial thromboembolism in patients with suspected or confirmed HIT who are treated with rivaroxaban. Methodological challenges faced in the design of this study include heterogeneity of the patient population, differences in the baseline risk of thrombosis and bleeding dependent on whether HIT is confirmed or just suspected, and heterogeneity in laboratory confirmation of HIT. The rationale for how these challenges were addressed and the final design of the Rivaroxaban for HIT study is reviewed.

Health Information Technology (HIT) Adaptation: Refocusing on the Journey to Successful HIT Implementation

PubMed Central

McAlearney, Ann Scheck; Sieck, Cynthia J; Hefner, Jennifer L; Huerta, Timothy R

2017-01-01

In past years, policies and regulations required hospitals to implement advanced capabilities of certified electronic health records (EHRs) in order to receive financial incentives. This has led to accelerated implementation of health information technologies (HIT) in health care settings. However, measures commonly used to evaluate the success of HIT implementation, such as HIT adoption, technology acceptance, and clinical quality, fail to account for complex sociotechnical variability across contexts and the different trajectories within organizations because of different implementation plans and timelines. We propose a new focus, HIT adaptation, to illuminate factors that facilitate or hinder the connection between use of the EHR and improved quality of care as well as to explore the trajectory of changes in the HIT implementation journey as it is impacted by frequent system upgrades and optimizations. Future research should develop instruments to evaluate the progress of HIT adaptation in both its longitudinal design and its focus on adaptation progress rather than on one cross-sectional outcome, allowing for more generalizability and knowledge transfer. PMID:28882812

Validation of the Headache Impact Test (HIT-6) in patients with chronic migraine.

PubMed

Rendas-Baum, Regina; Yang, Min; Varon, Sepideh F; Bloudek, Lisa M; DeGryse, Ronald E; Kosinski, Mark

2014-08-01

The Headache Impact Test (HIT)-6 was developed and has been validated in patients with various types of headache. The objective of this study was to report the psychometric properties of the HIT-6 among patients with chronic migraine. Data came from two international, multicenter, randomized, double-blind, placebo-controlled clinical trials of chronic migraine patients (N = 1,384) undergoing prophylaxis therapy. Confirmatory factor analysis and differential item functioning (DIF) analysis were used to test the latent structure and cross-cultural comparability of the HIT-6. Reliability, construct validity, and responsiveness were assessed. Two sets of criterion groups were used: (1) 28-day headache frequency: <10, 10-14, and ≥15 days; (2) sample quartiles of the total cumulative hours of headache: <140, 140 to <280, 280 to <420, and ≥420 hours. Two sets of responsiveness categories were defined as reduction of <30%, 30% to <50%, or ≥50% in (1) number of headache days and (2) cumulative hours of headache. Measurement invariance tests supported the stability of the HIT-6 latent structure across studies. DIF analysis supported cross-cultural comparability. Good reliability was observed across studies (Cronbach's α: 0.75-0.92; intraclass correlation coefficient: 0.76-0.80). HIT-6 scores correlated strongly (-0.86 to -0.59) with scores of the Migraine-Specific Quality-of-Life Questionnaire. Analysis of variance indicated that HIT-6 scores discriminated across both types of criterion groups (P<0.001), across studies and time points. HIT-6 change scores were significantly higher in magnitude in groups experiencing greater improvement (P<0.001). All measurement properties were consistently verified across the two studies, supporting the validity of the HIT-6 among chronic migraine patients. NCT00156910 and NCT00168428 on www.ClinicalTrials.gov.

Mental health and HIV sexual risk behavior among patrons of alcohol serving venues in Cape Town, South Africa.

PubMed

Sikkema, Kathleen J; Watt, Melissa H; Meade, Christina S; Ranby, Krista W; Kalichman, Seth C; Skinner, Donald; Pieterse, Desiree

2011-07-01

Alcohol-serving venues in South Africa provide a location for HIV prevention interventions due to risk factors of patrons in these establishments. Understanding the association between mental health and risk behaviors in these settings may inform interventions that address alcohol use and HIV prevention. Participants (n = 738) were surveyed in 6 alcohol-serving venues in Cape Town to assess post-traumatic stress disorder (PTSD) and depression symptoms, traumatic experiences, sexual behavior, and substance use. Logistic regression models examined whether traumatic experiences predicted PTSD and depression. Generalized linear models examined whether substance use, PTSD, and depressive symptoms predicted unprotected sexual intercourse. Men and women were analyzed separately. Participants exhibited high rates of traumatic experiences, PTSD, depression, alcohol consumption, and HIV risk behaviors. For men, PTSD was associated with being hit by a sex partner, physical child abuse, sexual child abuse and HIV diagnosis; depression was associated with being hit by a sex partner, forced sex and physical child abuse. For women, both PTSD and depression were associated with being hit by a sex partner, forced sex, and physical child abuse. Unprotected sexual intercourse was associated with age, frequency and quantity of alcohol use, drug use, and PTSD for men and frequency and quantity of alcohol use, depression, and PTSD for women. Mental health in this setting was poor and was associated with sexual risk behavior. Treating mental health and substance-use problems may aid in reducing HIV infection. Sexual assault prevention and treatment after sexual assault may strengthen HIV prevention efforts.

CHRR: coordinate hit-and-run with rounding for uniform sampling of constraint-based models.

PubMed

Haraldsdóttir, Hulda S; Cousins, Ben; Thiele, Ines; Fleming, Ronan M T; Vempala, Santosh

2017-06-01

In constraint-based metabolic modelling, physical and biochemical constraints define a polyhedral convex set of feasible flux vectors. Uniform sampling of this set provides an unbiased characterization of the metabolic capabilities of a biochemical network. However, reliable uniform sampling of genome-scale biochemical networks is challenging due to their high dimensionality and inherent anisotropy. Here, we present an implementation of a new sampling algorithm, coordinate hit-and-run with rounding (CHRR). This algorithm is based on the provably efficient hit-and-run random walk and crucially uses a preprocessing step to round the anisotropic flux set. CHRR provably converges to a uniform stationary sampling distribution. We apply it to metabolic networks of increasing dimensionality. We show that it converges several times faster than a popular artificial centering hit-and-run algorithm, enabling reliable and tractable sampling of genome-scale biochemical networks. https://github.com/opencobra/cobratoolbox . ronan.mt.fleming@gmail.com or vempala@cc.gatech.edu. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press.

Verification of Eulerian-Eulerian and Eulerian-Lagrangian simulations for fluid-particle flows

NASA Astrophysics Data System (ADS)

Kong, Bo; Patel, Ravi G.; Capecelatro, Jesse; Desjardins, Olivier; Fox, Rodney O.

2017-11-01

In this work, we study the performance of three simulation techniques for fluid-particle flows: (1) a volume-filtered Euler-Lagrange approach (EL), (2) a quadrature-based moment method using the anisotropic Gaussian closure (AG), and (3) a traditional two-fluid model. By simulating two problems: particles in frozen homogeneous isotropic turbulence (HIT), and cluster-induced turbulence (CIT), the convergence of the methods under grid refinement is found to depend on the simulation method and the specific problem, with CIT simulations facing fewer difficulties than HIT. Although EL converges under refinement for both HIT and CIT, its statistical results exhibit dependence on the techniques used to extract statistics for the particle phase. For HIT, converging both EE methods (TFM and AG) poses challenges, while for CIT, AG and EL produce similar results. Overall, all three methods face challenges when trying to extract converged, parameter-independent statistics due to the presence of shocks in the particle phase. National Science Foundation and National Energy Technology Laboratory.

Verification of Eulerian-Eulerian and Eulerian-Lagrangian simulations for turbulent fluid-particle flows

DOE PAGES

Patel, Ravi G.; Desjardins, Olivier; Kong, Bo; ...

2017-09-01

Here, we present a verification study of three simulation techniques for fluid–particle flows, including an Euler–Lagrange approach (EL) inspired by Jackson's seminal work on fluidized particles, a quadrature–based moment method based on the anisotropic Gaussian closure (AG), and the traditional two-fluid model. We perform simulations of two problems: particles in frozen homogeneous isotropic turbulence (HIT) and cluster-induced turbulence (CIT). For verification, we evaluate various techniques for extracting statistics from EL and study the convergence properties of the three methods under grid refinement. The convergence is found to depend on the simulation method and on the problem, with CIT simulations posingmore » fewer difficulties than HIT. Specifically, EL converges under refinement for both HIT and CIT, but statistics exhibit dependence on the postprocessing parameters. For CIT, AG produces similar results to EL. For HIT, converging both TFM and AG poses challenges. Overall, extracting converged, parameter-independent Eulerian statistics remains a challenge for all methods.« less

Verification of Eulerian-Eulerian and Eulerian-Lagrangian simulations for turbulent fluid-particle flows

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

Patel, Ravi G.; Desjardins, Olivier; Kong, Bo

Here, we present a verification study of three simulation techniques for fluid–particle flows, including an Euler–Lagrange approach (EL) inspired by Jackson's seminal work on fluidized particles, a quadrature–based moment method based on the anisotropic Gaussian closure (AG), and the traditional two-fluid model. We perform simulations of two problems: particles in frozen homogeneous isotropic turbulence (HIT) and cluster-induced turbulence (CIT). For verification, we evaluate various techniques for extracting statistics from EL and study the convergence properties of the three methods under grid refinement. The convergence is found to depend on the simulation method and on the problem, with CIT simulations posingmore » fewer difficulties than HIT. Specifically, EL converges under refinement for both HIT and CIT, but statistics exhibit dependence on the postprocessing parameters. For CIT, AG produces similar results to EL. For HIT, converging both TFM and AG poses challenges. Overall, extracting converged, parameter-independent Eulerian statistics remains a challenge for all methods.« less

Health information technology and sociotechnical systems: a progress report on recent developments within the UK National Health Service (NHS).

PubMed

Waterson, Patrick

2014-03-01

This paper summarises some of the research that Ken Eason and colleagues at Loughborough University have carried out in the last few years on the introduction of Health Information Technologies (HIT) within the UK National Health Service (NHS). In particular, the paper focuses on three examples which illustrate aspects of the introduction of HIT within the NHS and the role played by the UK National Programme for Information Technology (NPfIT). The studies focus on stages of planning and preparation, implementation and use, adaptation and evolution of HIT (e.g., electronic patient records, virtual wards) within primary, secondary and community care settings. Our findings point to a number of common themes which characterise the use of these systems. These include tensions between national and local strategies for implementing HIT and poor fit between healthcare work systems and the design of HIT. The findings are discussed in the light of other large-scale, national attempts to introduce similar technologies, as well as drawing out a set of wider lessons learnt from the NPfIT programme based on Ken Eason's earlier work and other research on the implementation of large-scale HIT. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.

[Diagnosis and treatment of heparin-induced thrombocytopenia (HIT) based on its atypical immunological features].

PubMed

Miyata, Shigeki; Maeda, Takuma

2016-03-01

Heparin-induced thrombocytopenia (HIT) is a prothrombotic side effect of heparin therapy caused by HIT antibodies, i.e., anti-platelet factor 4 (PF4)/heparin IgG with platelet-activating properties. For serological diagnosis, antigen immunoassays are commonly used worldwide. However, such assays do not indicate their platelet-activating properties, leading to low specificity for the HIT diagnosis. Therefore, over-diagnosis is currently the most serious problem associated with HIT. The detection of platelet-activating antibodies using a washed platelet activation assay is crucial for appropriate HIT diagnosis. Recent advances in our understanding of the pathogenesis of HIT include it having several clinical features atypical for an immune-mediated disease. Heparin-naïve patients can develop IgG antibodies as early as day 4, as in a secondary immune response. Evidence for an anamnestic response on heparin re-exposure is lacking. In addition, HIT antibodies are relatively short-lived, unlike those in a secondary immune response. These lines of evidence suggest that the mechanisms underlying HIT antibody formation may be compatible with a non-T cell-dependent immune reaction. These atypical clinical and serological features should be carefully considered while endeavoring to accurately diagnose HIT, which leads to appropriate therapies such as immediate administration of an alternative anticoagulant to prevent thromboembolic events and re-administration of heparin during surgery involving cardiopulmonary bypass when HIT antibodies are no longer detectable.

Performance Comparison of Two Gene Set Analysis Methods for Genome-wide Association Study Results: GSA-SNP vs i-GSEA4GWAS.

PubMed

Kwon, Ji-Sun; Kim, Jihye; Nam, Dougu; Kim, Sangsoo

2012-06-01

Gene set analysis (GSA) is useful in interpreting a genome-wide association study (GWAS) result in terms of biological mechanism. We compared the performance of two different GSA implementations that accept GWAS p-values of single nucleotide polymorphisms (SNPs) or gene-by-gene summaries thereof, GSA-SNP and i-GSEA4GWAS, under the same settings of inputs and parameters. GSA runs were made with two sets of p-values from a Korean type 2 diabetes mellitus GWAS study: 259,188 and 1,152,947 SNPs of the original and imputed genotype datasets, respectively. When Gene Ontology terms were used as gene sets, i-GSEA4GWAS produced 283 and 1,070 hits for the unimputed and imputed datasets, respectively. On the other hand, GSA-SNP reported 94 and 38 hits, respectively, for both datasets. Similar, but to a lesser degree, trends were observed with Kyoto Encyclopedia of Genes and Genomes (KEGG) gene sets as well. The huge number of hits by i-GSEA4GWAS for the imputed dataset was probably an artifact due to the scaling step in the algorithm. The decrease in hits by GSA-SNP for the imputed dataset may be due to the fact that it relies on Z-statistics, which is sensitive to variations in the background level of associations. Judicious evaluation of the GSA outcomes, perhaps based on multiple programs, is recommended.

Cryptotomography: reconstructing 3D Fourier intensities from randomly oriented single-shot diffraction patterns (CXIDB ID 9)

DOE Data Explorer

Loh, Ne-Te Duane

2011-08-01

These 2000 single-shot diffraction patterns include were either background-scattering only or hits (background-scattering plus diffraction signal from sub-micron ellipsoidal particles at random, undetermined orientations). Candidate hits were identified by eye, and the remainder were presumed as background. 54 usable, background-subtracted hits in this set (procedure in referenced article) were used to reconstruct the 3D diffraction intensities of the average ellipsoidal particle.

Health information technology and dynamic capabilities.

PubMed

Leung, Ricky C

2012-01-01

Health information technology (HIT) purports to increase quality and efficiency in health care organizations. However, health care organizations are situated in constantly changing environments. They need dynamic capabilities to implement HIT effectively. This article builds on the dynamic capabilities perspective and generates propositions about implementing HIT in dynamic environments. Specifically, I identify the (1) the necessary resources and capabilities for organizations to implement HIT; (2) the organizational capabilities and benefits that can be enhanced by HIT; and (3) the similarities and differences between three distinct forms of HIT. I synthesized the literature on dynamic capabilities and HIT to identify dynamic capabilities that are associated with (1) electronic medical records, (2) telemedicine, and (3) social media. In addition, I discuss the benefits of these HITs for improving the dynamic capabilities of health care organizations. PROPOSITIONS/FINDINGS: This article generates three sets of propositions that can be tested empirically. First, I am concerned with how organizational size and human resources affect successful implementation of HIT. In addition, I argue that three technology-specific factors--hospital type, medical specialty, and socially desirable technical features--may affect the implementation of HIT. To cope with constantly changing environmental pressures, health administrators need to deploy, modify, and/or acquire organizational resources skillfully. Practitioners need to identify dynamic capabilities to support specific forms of HIT and understand how HIT enables health care organizations in turn. The concept of evolutionary fitness in the dynamic capabilities perspective may be developed to measure HIT implementation.

Acceptance of health information technology in health professionals: an application of the revised technology acceptance model.

PubMed

Ketikidis, Panayiotis; Dimitrovski, Tomislav; Lazuras, Lambros; Bath, Peter A

2012-06-01

The response of health professionals to the use of health information technology (HIT) is an important research topic that can partly explain the success or failure of any HIT application. The present study applied a modified version of the revised technology acceptance model (TAM) to assess the relevant beliefs and acceptance of HIT systems in a sample of health professionals (n = 133). Structured anonymous questionnaires were used and a cross-sectional design was employed. The main outcome measure was the intention to use HIT systems. ANOVA was employed to examine differences in TAM-related variables between nurses and medical doctors, and no significant differences were found. Multiple linear regression analysis was used to assess the predictors of HIT usage intentions. The findings showed that perceived ease of use, but not usefulness, relevance and subjective norms directly predicted HIT usage intentions. The present findings suggest that a modification of the original TAM approach is needed to better understand health professionals' support and endorsement of HIT. Perceived ease of use, relevance of HIT to the medical and nursing professions, as well as social influences, should be tapped by information campaigns aiming to enhance support for HIT in healthcare settings.

Re-examining health IT policy: what will it take to derive value from our investment?

PubMed

Riskin, Loren; Koppel, Ross; Riskin, Daniel

2015-03-01

Despite substantial investments in health information technology (HIT), the nation's goals of reducing cost and improving outcomes through HIT remain elusive. This period of transition, with new Office of National Coordinator for HIT leadership, upcoming Meaningful Use Stage III definitions, and increasing congressional oversight, is opportune to consider needed course corrections in HIT strategy. This article describes current problems and recommended changes in HIT policy, including approaches to usability, interoperability, and quality measurement. Recommendations refrain from interim measures, such as electronic health record adoption rates, and instead focus on measurable national value to benefit the economy, to reduce healthcare costs, and to improve clinical efficiency and care quality. © The Author 2014. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Health Information Technology Coordination to Support Patient-centered Care Coordination.

PubMed

Steichen, O; Gregg, W

2015-08-13

To select papers published in 2014, illustrating how information technology can contribute to and improve patient-centered care coordination. The two section editors performed a literature review from Medline and Web of Science to select a list of candidate best papers on the use of information technology for patient-centered care coordination. These papers were peer-reviewed by external reviewers and three of them were selected as "best papers". The first selected paper reports a qualitative study exploring the gap between current practices of care coordination in various settings and idealized longitudinal care plans. The second selected paper illustrates several unintended consequences of HIT designed to improve care coordination. The third selected paper shows that advanced analytic techniques in medical informatics can be instrumental in studying patient-centered care coordination. The realization of true patient-centered care coordination is dependent upon a number of factors. Standardization of clinical documentation and HIT interoperability across organization and settings is a critical prerequisite for HIT to support patient-centered care coordination. Enabling patient involvement is an efficient means for goal setting and health information sharing. Additionally, unintended consequences of HIT tools (both positive and negative) must be measured and taken into account for quality improvement.

Examining Health Information Technology Implementation Success Factors in Critical Access Hospitals

ERIC Educational Resources Information Center

Monkman, Blake D.

2016-01-01

As the role of information technology increases throughout the world, healthcare providers in the United States face industry and governmental pressures to implement health information technology (HIT) as a tool to improve healthcare costs, quality, and safety. The problem addressed in this study was the relatively low HIT implementation success…

Visits, Hits, Caching and Counting on the World Wide Web: Old Wine in New Bottles?

ERIC Educational Resources Information Center

Berthon, Pierre; Pitt, Leyland; Prendergast, Gerard

1997-01-01

Although web browser caching speeds up retrieval, reduces network traffic, and decreases the load on servers and browser's computers, an unintended consequence for marketing research is that Web servers undercount hits. This article explores counting problems, caching, proxy servers, trawler software and presents a series of correction factors…

Discovery of a new chemical series of BRD4(1) inhibitors using protein-ligand docking and structure-guided design.

PubMed

Duffy, Bryan C; Liu, Shuang; Martin, Gregory S; Wang, Ruifang; Hsia, Ming Min; Zhao, He; Guo, Cheng; Ellis, Michael; Quinn, John F; Kharenko, Olesya A; Norek, Karen; Gesner, Emily M; Young, Peter R; McLure, Kevin G; Wagner, Gregory S; Lakshminarasimhan, Damodharan; White, Andre; Suto, Robert K; Hansen, Henrik C; Kitchen, Douglas B

2015-07-15

Bromodomains are key transcriptional regulators that are thought to be druggable epigenetic targets for cancer, inflammation, diabetes and cardiovascular therapeutics. Of particular importance is the first of two bromodomains in bromodomain containing 4 protein (BRD4(1)). Protein-ligand docking in BRD4(1) was used to purchase a small, focused screening set of compounds possessing a large variety of core structures. Within this set, a small number of weak hits each contained a dihydroquinoxalinone ring system. We purchased other analogs with this ring system and further validated the new hit series and obtained improvement in binding inhibition. Limited exploration by new analog synthesis showed that the binding inhibition in a FRET assay could be improved to the low μM level making this new core a potential hit-to-lead series. Additionally, the predicted geometries of the initial hit and an improved analog were confirmed by X-ray co-crystallography with BRD4(1). Copyright © 2015 Elsevier Ltd. All rights reserved.

Diffusion of information technology supporting the Institute of Medicine's quality chasm care aims.

PubMed

Burke, Darrell; Menachemi, Nir; Brooks, Robert G

2005-01-01

This article examines the degree to which healthcare information technology (HIT) supporting the Institute of Medicine's (IOM) six care aims is utilized in the hospital setting and explores organizational factors associated with HIT use. Guided by the IOM's Crossing the quality chasm report and associated literature, 27 applications and/or capabilities are classified according to one or more of the six care aims. A structured survey of Florida hospitals identified the use of HIT. Results suggest that, on average, hospitals have not yet embraced HIT to support the IOM's care aims and that associated organizational factors vary according to care aim.

Costs and benefits of health information technology.

PubMed

Shekelle, Paul G; Morton, Sally C; Keeler, Emmett B

2006-04-01

An evidence report was prepared to assess the evidence base regarding benefits and costs of health information technology (HIT) systems, that is, the value of discrete HIT functions and systems in various healthcare settings, particularly those providing pediatric care. PubMed, the Cochrane Controlled Clinical Trials Register, and the Cochrane Database of Reviews of Effectiveness (DARE) were electronically searched for articles published since 1995. Several reports prepared by private industry were also reviewed. Of 855 studies screened, 256 were included in the final analyses. These included systematic reviews, meta-analyses, studies that tested a hypothesis, and predictive analyses. Each article was reviewed independently by two reviewers; disagreement was resolved by consensus. Of the 256 studies, 156 concerned decision support, 84 assessed the electronic medical record, and 30 were about computerized physician order entry (categories are not mutually exclusive). One hundred twenty four of the studies assessed the effect of the HIT system in the outpatient or ambulatory setting; 82 assessed its use in the hospital or inpatient setting. Ninety-seven studies used a randomized design. There were 11 other controlled clinical trials, 33 studies using a pre-post design, and 20 studies using a time series. Another 17 were case studies with a concurrent control. Of the 211 hypothesis-testing studies, 82 contained at least some cost data. We identified no study or collection of studies, outside of those from a handful of HIT leaders, that would allow a reader to make a determination about the generalizable knowledge of the study's reported benefit. Beside these studies from HIT leaders, no other research assessed HIT systems that had comprehensive functionality and included data on costs, relevant information on organizational context and process change, and data on implementation. A small body of literature supports a role for HIT in improving the quality of pediatric care. Insufficient data were available on the costs or cost-effectiveness of implementing such systems. The ability of Electronic Health Records (EHRs) to improve the quality of care in ambulatory care settings was demonstrated in a small series of studies conducted at four sites (three U.S. medical centers and one in the Netherlands). The studies demonstrated improvements in provider performance when clinical information management and decision support tools were made available within an EHR system, particularly when the EHRs had the capacity to store data with high fidelity, to make those data readily accessible, and to help translate them into context-specific information that can empower providers in their work. Despite the heterogeneity in the analytic methods used, all cost-benefit analyses predicted substantial savings from EHR (and health care information exchange and interoperability) implementation: The quantifiable benefits are projected to outweigh the investment costs. However, the predicted time needed to break even varied from three to as many as 13 years. HIT has the potential to enable a dramatic transformation in the delivery of health care, making it safer, more effective, and more efficient. Some organizations have already realized major gains through the implementation of multifunctional, interoperable HIT systems built around an EHR. However, widespread implementation of HIT has been limited by a lack of generalizable knowledge about what types of HIT and implementation methods will improve care and manage costs for specific health organizations. The reporting of HIT development and implementation requires fuller descriptions of both the intervention and the organizational/economic environment in which it is implemented.

The One-on-One Stochastic Duel. Parts I and II

DTIC Science & Technology

1979-04-15

called the fundamental marksman problem (FM). From this we may solve the duel problem by considering each marksman to be firing independ- ently of the...other. The first to hit his passive target wins. This is entirely equivalent to the fundamental duel, a the model described above in no way links the...fire another round at t it muot fail, in order fo’" the system to be in the state of having just fired th a round which vas the n one, and no hits

Hypersensitivity to reward in problem gamblers.

PubMed

Hewig, Johannes; Kretschmer, Nora; Trippe, Ralf H; Hecht, Holger; Coles, Michael G H; Holroyd, Clay B; Miltner, Wolfgang H R

2010-04-15

Recent research has begun to examine the neurophysiologic basis of pathological gambling. However, direct evidence of a behavioral deficit and an accompanying neurofunctional deviation in a realistic gambling context such as Black Jack has not yet been reported. Electroencephalogram was recorded while 20 problem gamblers and 21 control participants played a computerized version of Black Jack. Participants were asked to decide at point scores between 11 and 21 whether they wanted to take another card ("hit") to arrive closer to 21 than the opponent (simulated by computer) or not to take another card ("sit") to avoid going over 21 ("bust"). At a critical point score of 16, problem gamblers decided more often to hit despite losses due to a bust on the preceding trial, whereas control participants decided more often to sit under these conditions. Furthermore, problem gamblers showed more reward-related positive amplitudes in the event-related brain potential than control participants after successful hit decisions at 16. Here we provide experimental evidence for high-risk taking behavior in gamblers and its correlate in event-related brain potentials. Our results suggest that high-risk-taking behavior in problem gamblers is associated with an increased reward-related neural response to infrequent successes of this behavior. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Unintended Consequences: New Problems, New Solutions. Contributions From 2015.

PubMed

Koppel, R; Chen, Y

2016-11-10

To select the best of the 2015 published papers on unintended consequences of healthcare information technology (HIT). Literature searches in several areas of scholarship, including IT, human factors, evaluation studies, medical errors, medical informatics, and implementation science. Also, because the specific terms "unintended consequences" were not often included in abstracts and titles, a more nuanced search algorithm was developed. We identified 754 papers that had some empirical research on unintended consequences of HIT. An initial screen of titles and abstracts reduced this to 171 papers of potential interest. We then further filtered out papers that did not meet the following criteria: 1) the paper had to report an original empirical investigation, and 2) the impact reported had to be not negligible, i.e., in quantitative studies, the results related to unintended consequences were statistically significant; and in qualitative studies the relevant themes emerged were prominent. This resulted in 33 papers of which 15 were selected as best paper candidates. Each of these 15 papers was then separately evaluated by four reviewers. The final selection of four papers was made jointly by the external reviewers and the two section editors. There is a growing awareness of the importance of HIT's unintended consequences-be they generated by the HIT vendors, the implementation process, the consultants, the users, or most probably, some combination of the above. There has also been greater creativity in use of data sources, including secondary data (e.g., medical malpractice cases and surveys) and a wider acceptance of mixed methods to identify unintended consequences. Unfortunately, the complexity of causes mitigates the value of recommendations to avoid unwanted outcomes. Suggestions are often contentious rather than obvious, setting-specific, and not universally applicable. "Lessons learned" often take on generalized-and perhaps platitudinous-forms, such as: "plan extra time," "involve all of the stakeholders," "recognize the different needs of different units or disciplines." The greater awareness of these problems, and the increased desire to identify and eliminate them is clearly reflected in the area's growing literature. We are hopeful the topic will receive additional attention and the discipline will improve its ability to identify and address these unexpected and usually adverse outcomes.

Health Information Technology (HIT) Adaptation: Refocusing on the Journey to Successful HIT Implementation.

PubMed

Yen, Po-Yin; McAlearney, Ann Scheck; Sieck, Cynthia J; Hefner, Jennifer L; Huerta, Timothy R

2017-09-07

In past years, policies and regulations required hospitals to implement advanced capabilities of certified electronic health records (EHRs) in order to receive financial incentives. This has led to accelerated implementation of health information technologies (HIT) in health care settings. However, measures commonly used to evaluate the success of HIT implementation, such as HIT adoption, technology acceptance, and clinical quality, fail to account for complex sociotechnical variability across contexts and the different trajectories within organizations because of different implementation plans and timelines. We propose a new focus, HIT adaptation, to illuminate factors that facilitate or hinder the connection between use of the EHR and improved quality of care as well as to explore the trajectory of changes in the HIT implementation journey as it is impacted by frequent system upgrades and optimizations. Future research should develop instruments to evaluate the progress of HIT adaptation in both its longitudinal design and its focus on adaptation progress rather than on one cross-sectional outcome, allowing for more generalizability and knowledge transfer. ©Po-Yin Yen, Ann Scheck McAlearney, Cynthia J Sieck, Jennifer L Hefner, Timothy R Huerta. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 07.09.2017.

Bioturbo similarity searching: combining chemical and biological similarity to discover structurally diverse bioactive molecules.

PubMed

Wassermann, Anne Mai; Lounkine, Eugen; Glick, Meir

2013-03-25

Virtual screening using bioactivity profiles has become an integral part of currently applied hit finding methods in pharmaceutical industry. However, a significant drawback of this approach is that it is only applicable to compounds that have been biologically tested in the past and have sufficient activity annotations for meaningful profile comparisons. Although bioactivity data generated in pharmaceutical institutions are growing on an unprecedented scale, the number of biologically annotated compounds still covers only a minuscule fraction of chemical space. For a newly synthesized compound or an isolated natural product to be biologically characterized across multiple assays, it may take a considerable amount of time. Consequently, this chemical matter will not be included in virtual screening campaigns based on bioactivity profiles. To overcome this problem, we herein introduce bioturbo similarity searching that uses chemical similarity to map molecules without biological annotations into bioactivity space and then searches for biologically similar compounds in this reference system. In benchmark calculations on primary screening data, we demonstrate that our approach generally achieves higher hit rates and identifies structurally more diverse compounds than approaches using chemical information only. Furthermore, our method is able to discover hits with novel modes of inhibition that traditional 2D and 3D similarity approaches are unlikely to discover. Test calculations on a set of natural products reveal the practical utility of the approach for identifying novel and synthetically more accessible chemical matter.

Hit and lead criteria in drug discovery for infectious diseases of the developing world.

PubMed

Katsuno, Kei; Burrows, Jeremy N; Duncan, Ken; Hooft van Huijsduijnen, Rob; Kaneko, Takushi; Kita, Kiyoshi; Mowbray, Charles E; Schmatz, Dennis; Warner, Peter; Slingsby, B T

2015-11-01

Reducing the burden of infectious diseases that affect people in the developing world requires sustained collaborative drug discovery efforts. The quality of the chemical starting points for such projects is a key factor in improving the likelihood of clinical success, and so it is important to set clear go/no-go criteria for the progression of hit and lead compounds. With this in mind, the Japanese Global Health Innovative Technology (GHIT) Fund convened with experts from the Medicines for Malaria Venture, the Drugs for Neglected Diseases initiative and the TB Alliance, together with representatives from the Bill &Melinda Gates Foundation, to set disease-specific criteria for hits and leads for malaria, tuberculosis, visceral leishmaniasis and Chagas disease. Here, we present the agreed criteria and discuss the underlying rationale.

Building on a national health information technology strategic plan for long-term and post-acute care: comments by the Long Term Post Acute Care Health Information Technology Collaborative.

PubMed

Alexander, Gregory L; Alwan, Majd; Batshon, Lynne; Bloom, Shawn M; Brennan, Richard D; Derr, John F; Dougherty, Michelle; Gruhn, Peter; Kirby, Annessa; Manard, Barbara; Raiford, Robin; Serio, Ingrid Johnson

2011-07-01

The LTPAC (Long Term Post Acute Care) Health Information Technology (HIT) Collaborative consists of an alliance of long-term services and post-acute care stakeholders. Members of the collaborative are actively promoting HIT innovations in long-term care settings because IT adoption for health care institutions in the United States has become a high priority. One method used to actively promote HIT is providing expert comments on important documents addressing HIT adoption. Recently, the Office of the National Coordinator for HIT released a draft of the Federal Health Information Technology Strategic Plan 2011-2015 for public comment. The following brief is intended to inform about recommendations and comments made by the Collaborative on the strategic plan. Copyright 2011, SLACK Incorporated.

The Association between Health Information Technology Adoption and Family Physicians' Practice Patterns in Canada: Evidence from 2007 and 2010 National Physician Surveys

PubMed Central

Sarma, Sisira; Hajizadeh, Mohammad; Thind, Amardeep; Chan, Rick

2013-01-01

Objective: To describe the association between health information technology (HIT) adoption and family physicians' patient visit length in Canada after controlling for physician and practice characteristics. Method: HIT adoption is defined in terms of four types of HIT usage: no HIT use (NO), basic HIT use without electronic medical record system (HIT), basic HIT use with electronic medical record (EMR) and advanced HIT use (EMR + HIT). The outcome variable is the average time spent on a patient visit (visit length). The data for this study came from the 2007 and 2010 National Physician Surveys. A log-linear model was used to analyze our visit length outcome. Results: The average time worked per week was found to be in the neighbourhood of 36 hours in both 2007 and 2010, but users of EMR and EMR + HIT were undertaking fewer patient visits per week relative to NO users. Multivariable analysis showed that EMR and EMR + HIT were associated with longer average time spent per patient visit by about 7.7% (p<0.05) and 6.7% (p<0.01), respectively, compared to NO users in 2007. In 2010, EMR was not statistically significant and EMR + HIT was associated with a 4% (p<0.1) increased visit length. A variety of practice-related variables such as the mode of remuneration, work setting and interprofessional practice influenced visit length in the expected direction. Conclusion: Use of HIT is found to be associated with fewer patient visits and longer visit length among family physicians in Canada relative to NO users, but this association weakened in the multivariable analysis of 2010. PMID:23968677

Donation, Not Disease! A Multiple-Hit Hypothesis on Development of Post-Donation Kidney Disease.

PubMed

Cheng, Xingxing S; Glassock, Richard J; Lentine, Krista L; Chertow, Glenn M; Tan, Jane C

2017-01-01

The risks following living kidney donation has been the subject of rigorous investigation in the past several decades. How to utilize the burgeoning new knowledge base to better the risk assessment, education, and health maintenance of donors is unclear. We review the physiologic and epidemiologic evidences on the post-donation state and submit a multiple-hit hypothesis to reconcile the finite elevation in risk of kidney disease after donation with the benign course of most kidney donors. The risk of end-stage kidney disease is higher in kidney donors compared to similarly healthy non-kidney donors. Nonetheless, post-donation kidney disease is uncommon and arises mostly in the setting of other "hits"-either a "first hit" present at birth or a "second hit" acquired later in life. The transplant community's focus should be directed toward (1) personalized risk assessment to inform consent before donation and (2) preventing and treating development of "second hits" following kidney donation.

The e-health implementation toolkit: qualitative evaluation across four European countries

PubMed Central

2011-01-01

Background Implementation researchers have attempted to overcome the research-practice gap in e-health by developing tools that summarize and synthesize research evidence of factors that impede or facilitate implementation of innovation in healthcare settings. The e-Health Implementation Toolkit (e-HIT) is an example of such a tool that was designed within the context of the United Kingdom National Health Service to promote implementation of e-health services. Its utility in international settings is unknown. Methods We conducted a qualitative evaluation of the e-HIT in use across four countries--Finland, Norway, Scotland, and Sweden. Data were generated using a combination of interview approaches (n = 22) to document e-HIT users' experiences of the tool to guide decision making about the selection of e-health pilot services and to monitor their progress over time. Results e-HIT users evaluated the tool positively in terms of its scope to organize and enhance their critical thinking about their implementation work and, importantly, to facilitate discussion between those involved in that work. It was easy to use in either its paper- or web-based format, and its visual elements were positively received. There were some minor criticisms of the e-HIT with some suggestions for content changes and comments about its design as a generic tool (rather than specific to sites and e-health services). However, overall, e-HIT users considered it to be a highly workable tool that they found useful, which they would use again, and which they would recommend to other e-health implementers. Conclusion The use of the e-HIT is feasible and acceptable in a range of international contexts by a range of professionals for a range of different e-health systems. PMID:22098945

The e-Health Implementation Toolkit: qualitative evaluation across four European countries.

PubMed

MacFarlane, Anne; Clerkin, Pauline; Murray, Elizabeth; Heaney, David J; Wakeling, Mary; Pesola, Ulla-Maija; Waterworth, Eva Lindh; Larsen, Frank; Makiniemi, Minna; Winblad, Ilkka

2011-11-19

Implementation researchers have attempted to overcome the research-practice gap in e-health by developing tools that summarize and synthesize research evidence of factors that impede or facilitate implementation of innovation in healthcare settings. The e-Health Implementation Toolkit (e-HIT) is an example of such a tool that was designed within the context of the United Kingdom National Health Service to promote implementation of e-health services. Its utility in international settings is unknown. We conducted a qualitative evaluation of the e-HIT in use across four countries--Finland, Norway, Scotland, and Sweden. Data were generated using a combination of interview approaches (n = 22) to document e-HIT users' experiences of the tool to guide decision making about the selection of e-health pilot services and to monitor their progress over time. e-HIT users evaluated the tool positively in terms of its scope to organize and enhance their critical thinking about their implementation work and, importantly, to facilitate discussion between those involved in that work. It was easy to use in either its paper- or web-based format, and its visual elements were positively received. There were some minor criticisms of the e-HIT with some suggestions for content changes and comments about its design as a generic tool (rather than specific to sites and e-health services). However, overall, e-HIT users considered it to be a highly workable tool that they found useful, which they would use again, and which they would recommend to other e-health implementers. The use of the e-HIT is feasible and acceptable in a range of international contexts by a range of professionals for a range of different e-health systems.

Use of health information technology (HIT) to improve statin adherence and low-density lipoprotein cholesterol goal attainment in high-risk patients: proceedings from a workshop.

PubMed

Cohen, Jerome D; Aspry, Karen E; Brown, Alan S; Foody, Joanne M; Furman, Roy; Jacobson, Terry A; Karalis, Dean G; Kris-Etherton, Penny M; Laforge, Ralph; O'Toole, Michael F; Scott, Ronald D; Underberg, James A; Valuck, Thomas B; Willard, Kaye-Eileen; Ziajka, Paul E; Ito, Matthew K

2013-01-01

The workshop discussions focused on how low-density lipoprotein cholesterol (LDL-C) goal attainment can be enhanced with the use of health information technology (HIT) in different clinical settings. A gap is acknowledged in LDL-C goal attainment, but because of the passage of the American Recovery & Reinvestment Act and the Health Information Technology for Economic and Clinical Health Acts there is now reason for optimism that this gap can be narrowed. For HIT to be effectively used to achieve treatment goals, it must be implemented in a setting in which the health care team is fully committed to achieving these goals. Implementation of HIT alone has not resulted in reducing the gap. It is critical to build an effective management strategy into the HIT platform without increasing the overall work/time burden on staff. By enhancing communication between the health care team and the patient, more timely adjustments to treatment plans can be made with greater opportunity for LDL-C goal attainment and improved efficiency in the long run. Patients would be encouraged to take a more active role. Support tools are available. The National Lipid Association has developed a toolkit designed to improve patient compliance and could be modified for use in an HIT system. The importance of a collaborative approach between nongovernmental organizations such as the National Lipid Association, National Quality Forum, HIT partners, and other members of the health care industry offers the best opportunity for long-term success and the real possibility that such efforts could be applied to other chronic conditions, for example, diabetes and hypertension. Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Nominal ISOMERs (Incorrect Spellings Of Medicines Eluding Researchers)—variants in the spellings of drug names in PubMed: a database review

PubMed Central

Aronson, Jeffrey K

2016-01-01

Objective To examine how misspellings of drug names could impede searches for published literature. Design Database review. Data source PubMed. Review methods The study included 30 drug names that are commonly misspelt on prescription charts in hospitals in Birmingham, UK (test set), and 30 control names randomly chosen from a hospital formulary (control set). The following definitions were used: standard names—the international non-proprietary names, variant names—deviations in spelling from standard names that are not themselves standard names in English language nomenclature, and hidden reference variants—variant spellings that identified publications in textword (tw) searches of PubMed or other databases, and which were not identified by textword searches for the standard names. Variant names were generated from standard names by applying letter substitutions, omissions, additions, transpositions, duplications, deduplications, and combinations of these. Searches were carried out in PubMed (30 June 2016) for “standard name[tw]” and “variant name[tw] NOT standard name[tw].” Results The 30 standard names of drugs in the test set gave 325 979 hits in total, and 160 hidden reference variants gave 3872 hits (1.17%). The standard names of the control set gave 470 064 hits, and 79 hidden reference variants gave 766 hits (0.16%). Letter substitutions (particularly i to y and vice versa) and omissions together accounted for 2924 (74%) of the variants. Amitriptyline (8530 hits) yielded 18 hidden reference variants (179 (2.1%) hits). Names ending in “in,” “ine,” or “micin” were commonly misspelt. Failing to search for hidden reference variants of “gentamicin,” “amitriptyline,” “mirtazapine,” and “trazodone” would miss at least 19 systematic reviews. A hidden reference variant related to Christmas, “No-el”, was rare; variants of “X-miss” were rarer. Conclusion When performing searches, researchers should include misspellings of drug names among their search terms. PMID:27974346

Nominal ISOMERs (Incorrect Spellings Of Medicines Eluding Researchers)-variants in the spellings of drug names in PubMed: a database review.

PubMed

Ferner, Robin E; Aronson, Jeffrey K

2016-12-14

 To examine how misspellings of drug names could impede searches for published literature.  Database review.  PubMed.  The study included 30 drug names that are commonly misspelt on prescription charts in hospitals in Birmingham, UK (test set), and 30 control names randomly chosen from a hospital formulary (control set). The following definitions were used: standard names-the international non-proprietary names, variant names-deviations in spelling from standard names that are not themselves standard names in English language nomenclature, and hidden reference variants-variant spellings that identified publications in textword (tw) searches of PubMed or other databases, and which were not identified by textword searches for the standard names. Variant names were generated from standard names by applying letter substitutions, omissions, additions, transpositions, duplications, deduplications, and combinations of these. Searches were carried out in PubMed (30 June 2016) for "standard name[tw]" and "variant name[tw] NOT standard name[tw]."  The 30 standard names of drugs in the test set gave 325 979 hits in total, and 160 hidden reference variants gave 3872 hits (1.17%). The standard names of the control set gave 470 064 hits, and 79 hidden reference variants gave 766 hits (0.16%). Letter substitutions (particularly i to y and vice versa) and omissions together accounted for 2924 (74%) of the variants. Amitriptyline (8530 hits) yielded 18 hidden reference variants (179 (2.1%) hits). Names ending in "in," "ine," or "micin" were commonly misspelt. Failing to search for hidden reference variants of "gentamicin," "amitriptyline," "mirtazapine," and "trazodone" would miss at least 19 systematic reviews. A hidden reference variant related to Christmas, "No-el", was rare; variants of "X-miss" were rarer.  When performing searches, researchers should include misspellings of drug names among their search terms. 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.

Simulation of a Real-Time Brain Computer Interface for Detecting a Self-Paced Hitting Task.

PubMed

Hammad, Sofyan H; Kamavuako, Ernest N; Farina, Dario; Jensen, Winnie

2016-12-01

An invasive brain-computer interface (BCI) is a promising neurorehabilitation device for severely disabled patients. Although some systems have been shown to work well in restricted laboratory settings, their utility must be tested in less controlled, real-time environments. Our objective was to investigate whether a specific motor task could be reliably detected from multiunit intracortical signals from freely moving animals in a simulated, real-time setting. Intracortical signals were first obtained from electrodes placed in the primary motor cortex of four rats that were trained to hit a retractable paddle (defined as a "Hit"). In the simulated real-time setting, the signal-to-noise-ratio was first increased by wavelet denoising. Action potentials were detected, and features were extracted (spike count, mean absolute values, entropy, and combination of these features) within pre-defined time windows (200 ms, 300 ms, and 400 ms) to classify the occurrence of a "Hit." We found higher detection accuracy of a "Hit" (73.1%, 73.4%, and 67.9% for the three window sizes, respectively) when the decision was made based on a combination of features rather than on a single feature. However, the duration of the window length was not statistically significant (p = 0.5). Our results showed the feasibility of detecting a motor task in real time in a less restricted environment compared to environments commonly applied within invasive BCI research, and they showed the feasibility of using information extracted from multiunit recordings, thereby avoiding the time-consuming and complex task of extracting and sorting single units. © 2016 International Neuromodulation Society.

Design, synthesis and screening studies of potent thiazol-2-amine derivatives as fibroblast growth factor receptor 1 inhibitors.

PubMed

Kumar, B V S Suneel; Lakshmi, Narasu; Kumar, M Ravi; Rambabu, Gundla; Manjashetty, Thimmappa H; Arunasree, Kalle M; Sriram, Dharmarajan; Ramkumar, Kavya; Neamati, Nouri; Dayam, Raveendra; Sarma, J A R P

2014-01-01

Fibroblast growth factor receptor 1 (FGFR1) a tyrosine kinase receptor, plays important roles in angiogenesis, embryonic development, cell proliferation, cell differentiation, and wound healing. The FGFR isoforms and their receptors (FGFRs) considered as a potential targets and under intense research to design potential anticancer agents. Fibroblast growth factors (FGF's) and its growth factor receptors (FGFR) plays vital role in one of the critical pathway in monitoring angiogenesis. In the current study, quantitative pharmacophore models were generated and validated using known FGFR1 inhibitors. The pharmacophore models were generated using a set of 28 compounds (training). The top pharmacophore model was selected and validated using a set of 126 compounds (test set) and also using external validation. The validated pharmacophore was considered as a virtual screening query to screen a database of 400,000 virtual molecules and pharmacophore model retrieved 2800 hits. The retrieved hits were subsequently filtered based on the fit value. The selected hits were subjected for docking studies to observe the binding modes of the retrieved hits and also to reduce the false positives. One of the potential hits (thiazole-2-amine derivative) was selected based the pharmacophore fit value, dock score, and synthetic feasibility. A few analogues of the thiazole-2-amine derivative were synthesized. These compounds were screened for FGFR1 activity and anti-proliferative studies. The top active compound showed 56.87% inhibition of FGFR1 activity at 50 µM and also showed good cellular activity. Further optimization of thiazole-2-amine derivatives is in progress.

Well There’s Your Problem: Isolating the Crash-Inducing Bits in a Fuzzed File

DTIC Science & Technology

2012-10-01

CurrHD end for for all CDChance[i] do Calculate Phit [i] [see (7)] BitReduction[i] ← CurrHD × CDChance[i] ExpectedReduction[i] ← Phit [i...at least one hit left to be found in the search space. Here we use the identity that phit = 1 — pmiss (14) and observe that the chance of getting...at least one hit in x tries is P (≥ 1_hit_in_ x_ tries) = 1 – pxmiss =1 − (1 − phit )x (15) Another way to interpret equation (15) is that if we try x

Quantum algorithms for Gibbs sampling and hitting-time estimation

DOE PAGES

Chowdhury, Anirban Narayan; Somma, Rolando D.

2017-02-01

In this paper, we present quantum algorithms for solving two problems regarding stochastic processes. The first algorithm prepares the thermal Gibbs state of a quantum system and runs in time almost linear in √Nβ/Ζ and polynomial in log(1/ϵ), where N is the Hilbert space dimension, β is the inverse temperature, Ζ is the partition function, and ϵ is the desired precision of the output state. Our quantum algorithm exponentially improves the dependence on 1/ϵ and quadratically improves the dependence on β of known quantum algorithms for this problem. The second algorithm estimates the hitting time of a Markov chain. Formore » a sparse stochastic matrix Ρ, it runs in time almost linear in 1/(ϵΔ 3/2), where ϵ is the absolute precision in the estimation and Δ is a parameter determined by Ρ, and whose inverse is an upper bound of the hitting time. Our quantum algorithm quadratically improves the dependence on 1/ϵ and 1/Δ of the analog classical algorithm for hitting-time estimation. Finally, both algorithms use tools recently developed in the context of Hamiltonian simulation, spectral gap amplification, and solving linear systems of equations.« less

NIMROD Simulations of the HIT-SI and HIT-SI3 Devices

NASA Astrophysics Data System (ADS)

Morgan, Kyle; Jarboe, Tom; Hossack, Aaron; Chandra, Rian; Everson, Chris

2017-10-01

The Helicity Injected Torus with Steady Inductive helicity injection (HIT-SI) experiment uses a set of inductively driven helicity injectors to apply non-axisymmetric current drive on the edge of the plasma, driving an axisymmetric spheromak equilibrium in a central confinement volume. Significant improvements have been made to extended MHD modeling of HIT-SI, with both the resolution of disagreement at high injector frequencies in HIT-SI in addition to successes with the new upgraded HIT-SI3 device. Previous numerical studies of HIT-SI, using a zero-beta eMHD model, focused on operations with a drive frequency of 14.5 kHz, and found reduced agreement with both the magnetic profile and current amplification at higher frequencies (30-70 kHz). HIT-SI3 has three helicity injectors which are able to operate with different mode structures of perturbations through the different relative temporal phasing of the injectors. Simulations that allow for pressure gradients have been performed in the parameter regimes of both devices using the NIMROD code and show improved agreement with experimental results, most notably capturing the observed Shafranov-shift due to increased beta observed at higher finj in HIT-SI and the variety of toroidal perturbation spectra available in HIT-SI3. This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Fusion Energy Sciences under Award Number DE-FG02- 96ER54361.

Statistical properties and pre-hit dynamics of price limit hits in the Chinese stock markets.

PubMed

Wan, Yu-Lei; Xie, Wen-Jie; Gu, Gao-Feng; Jiang, Zhi-Qiang; Chen, Wei; Xiong, Xiong; Zhang, Wei; Zhou, Wei-Xing

2015-01-01

Price limit trading rules are adopted in some stock markets (especially emerging markets) trying to cool off traders' short-term trading mania on individual stocks and increase market efficiency. Under such a microstructure, stocks may hit their up-limits and down-limits from time to time. However, the behaviors of price limit hits are not well studied partially due to the fact that main stock markets such as the US markets and most European markets do not set price limits. Here, we perform detailed analyses of the high-frequency data of all A-share common stocks traded on the Shanghai Stock Exchange and the Shenzhen Stock Exchange from 2000 to 2011 to investigate the statistical properties of price limit hits and the dynamical evolution of several important financial variables before stock price hits its limits. We compare the properties of up-limit hits and down-limit hits. We also divide the whole period into three bullish periods and three bearish periods to unveil possible differences during bullish and bearish market states. To uncover the impacts of stock capitalization on price limit hits, we partition all stocks into six portfolios according to their capitalizations on different trading days. We find that the price limit trading rule has a cooling-off effect (object to the magnet effect), indicating that the rule takes effect in the Chinese stock markets. We find that price continuation is much more likely to occur than price reversal on the next trading day after a limit-hitting day, especially for down-limit hits, which has potential practical values for market practitioners.

Technological iatrogenesis: the manifestation of inadequate organizational planning and the integration of health information technology.

PubMed

Palmieri, Patrick Albert; Peterson, Lori T; Corazzo, Luciano Bedoya

2011-01-01

The Institute of Medicine (IOM) views Health Information Technology (HIT) as an essential organizational prerequisite for the delivery of safe, reliable, and cost-effective health services. However, HIT presents the proverbial double-edged sword in generating solutions to improve system performance while facilitating the genesis of novel iatrogenic problems. Incongruent organizational processes give rise to technological iatrogenesis or the unintended consequences to system integrity and the resulting organizational outcomes potentiated by incongruent organizational-technological interfaces. HIT is a disruptive innovation for health services organizations but remains an overlooked organizational development (OD) concern. Recognizing the technology-organizational misalignments that result from HIT adoption is important for leaders seeking to eliminate sources of system instability. The Health Information Technology Iatrogenesis Model (HITIM) provides leaders with a conceptual framework from which to consider HIT as an instrument for organizational development. Complexity and Diffusion of Innovation theories support the framework that suggests each HIT adoption functions as a technological change agent. As such, leaders need to provide operational oversight to managers undertaking system change via HIT implementation. Traditional risk management tools, such as Failure Mode Effect Analysis and Root Cause Analysis, provide proactive pre- and post-implementation appraisals to verify system stability and to enhance system reliability. Reconsidering the use of these tools within the context of a new framework offers leaders guidance when adopting HIT to achieve performance improvement and better outcomes.

Usability Methods for Ensuring Health Information Technology Safety: Evidence-Based Approaches. Contribution of the IMIA Working Group Health Informatics for Patient Safety.

PubMed

Borycki, E; Kushniruk, A; Nohr, C; Takeda, H; Kuwata, S; Carvalho, C; Bainbridge, M; Kannry, J

2013-01-01

Issues related to lack of system usability and potential safety hazards continue to be reported in the health information technology (HIT) literature. Usability engineering methods are increasingly used to ensure improved system usability and they are also beginning to be applied more widely for ensuring the safety of HIT applications. These methods are being used in the design and implementation of many HIT systems. In this paper we describe evidence-based approaches to applying usability engineering methods. A multi-phased approach to ensuring system usability and safety in healthcare is described. Usability inspection methods are first described including the development of evidence-based safety heuristics for HIT. Laboratory-based usability testing is then conducted under artificial conditions to test if a system has any base level usability problems that need to be corrected. Usability problems that are detected are corrected and then a new phase is initiated where the system is tested under more realistic conditions using clinical simulations. This phase may involve testing the system with simulated patients. Finally, an additional phase may be conducted, involving a naturalistic study of system use under real-world clinical conditions. The methods described have been employed in the analysis of the usability and safety of a wide range of HIT applications, including electronic health record systems, decision support systems and consumer health applications. It has been found that at least usability inspection and usability testing should be applied prior to the widespread release of HIT. However, wherever possible, additional layers of testing involving clinical simulations and a naturalistic evaluation will likely detect usability and safety issues that may not otherwise be detected prior to widespread system release. The framework presented in the paper can be applied in order to develop more usable and safer HIT, based on multiple layers of evidence.

Video observation in HIT development: lessons learned on benefits and challenges.

PubMed

Høstgaard, Anna Marie; Bertelsen, Pernille

2012-08-22

Experience shows that the precondition for the development of successful health information technologies is a thorough insight into clinical work practice. In contemporary clinical work practice, clinical work and health information technology are integrated, and part of the practice is tacit. When work practice becomes routine, it slips to the background of the conscious awareness and becomes difficult to recognize without the context to support recall. This means that it is difficult to capture with traditional ethnographic research methods or in usability laboratories or clinical set ups. Observation by the use of the video technique within healthcare settings has proven to be capable of providing a thorough insight into the complex clinical work practice and its context - including parts of the tacit practice. The objective of this paper is 1) to argue for the video observation technique to inform and improve health-information-technology development and 2) to share insights and lessons learned on benefits and challenges when using the video observation technique within healthcare settings. A multiple case study including nine case studies conducted by DaCHI researchers 2004-2011 using audio-visual, non-participant video observation for data collection within different healthcare settings. In HIT development, video observation is beneficial for 1) informing and improving system design 2) studying changes in work practice 3) identifying new potentials and 4) documenting current work practices. The video observation technique used within healthcare settings is superior to other ethnographic research methods when it comes to disclosing the complexity in clinical work practice. The insights gained are far more realistic compared to traditional ethnographic studies or usability studies and studies in clinical set ups. Besides, the data generated through video recordings provide a solid basis for dialog between the health care professionals involved. The most important lessons learned are that a well considered methodology and clear formulated objectives are imperative, in order to stay focused during the data rich analysis phase. Additionally, the video observation technique is primarily recommended for studies of specific clinical work practices within delimited clinical settings. Overall, the video observation technique has proven to be capable of improving our understanding of the interwoven relation between clinical work practice and HIT and to inform us about user requirements and needs for HIT, which is a precondition for the development of more successful HIT systems in the future.

News Competition: Physics Olympiad hits Thailand Report: Institute carries out survey into maths in physics at university Event: A day for everyone teaching physics Conference: Welsh conference celebrates birthday Schools: Researchers in Residence scheme set to close Teachers: A day for new physics teachers Social: Network combines fun and physics Forthcoming events

NASA Astrophysics Data System (ADS)

2011-09-01

Competition: Physics Olympiad hits Thailand Report: Institute carries out survey into maths in physics at university Event: A day for everyone teaching physics Conference: Welsh conference celebrates birthday Schools: Researchers in Residence scheme set to close Teachers: A day for new physics teachers Social: Network combines fun and physics Forthcoming events

Evaluation of heparin-induced thrombocytopenia (HIT) laboratory testing and the 4Ts scoring system in the intensive care unit.

PubMed

Pierce, Wesly; Mazur, Joseph; Greenberg, Charles; Mueller, Joan; Foster, Joyce; Lazarchick, John

2013-01-01

Over-diagnosis of heparin-induced thrombocytopenia (HIT) results in costly and unnecessary laboratory screening and treatment with direct thrombin inhibitors. Our aim was to evaluate the utility of the 4Ts scoring system to predict HIT in multiple ICU settings and to characterize our treatment of these cases. Eighty-two patients from multiple ICU settings who underwent laboratory testing for HIT were classified as low-, intermediate-, or high-risk patients based on retrospectively adjudicated 4Ts scores. These results were compared with platelet-factor 4 enzyme-linked immunosorbent assays (PF4 ELISAs), optical density (OD) values, and serotonin-release assays (SRAs) to assess the utility of the 4Ts score to rule out ICU-related HIT and reduce laboratory and drug expenditures. Of the 82 patients reviewed, only 12 (11.4%) were PF4-positive and only 1 (1.2%) was SRA-positive for HIT. Heparin was discontinued in only 63.4% of patients suspected to have HIT. There were no significant differences in mean day of platelet fall, mean platelet nadir, and mean percent fall in platelet count between PF4-positive and negative patients (all p > 0.2). There was, however, a significantly higher proportion of patients with an intermediate to high 4Ts score in the PF4-positive group than in the PF4-negative group (66% vs. 30%, respectively; p = 0.02). The mean PF4 OD value in patients with intermediate to high 4Ts scores was significantly higher than in patients with low 4Ts scores (0.658 vs. 0.258, respectively; p < 0.001). The negative predictive values of the 4Ts score relative to the PF4 and SRA were 92% and 100%, respectively. The estimated laboratory and pharmacologic cost avoidance potential of the scoring system in this cohort was $21,450. Our modified 4Ts scoring system appears to be an effective tool for predicting HIT in the ICU and could avoid significant drug and laboratory expenditures if implemented prospectively. The clinical management of patients suspected of HIT is highly variable at our institution. Clinical protocols and education encouraging the proper identification and treatment of suspected HIT need to be established.

Smooth particle hydrodynamic modeling and validation for impact bird substitution

NASA Astrophysics Data System (ADS)

Babu, Arun; Prasad, Ganesh

2018-04-01

Bird strike events incidentally occur and can at times be fatal for air frame structures. Federal Aviation Regulations (FAR) and such other ones mandates aircrafts to be modeled to withstand various levels of bird hit damages. The subject matter of this paper is numerical modeling of a soft body geometry for realistically substituting an actual bird for carrying out simulations of bird hit on target structures. Evolution of such a numerical code to effect an actual bird behavior through impact is much desired for making use of the state of the art computational facilities in simulating bird strike events. Validity, of simulations depicting bird hits, is largely dependent on the correctness of the bird model. In an impact, a set of complex and coupled dynamic interaction exists between the target and the impactor. To simplify this problem, impactor response needs to be decoupled from that of the target. This can be done by assuming and modeling the target as noncompliant. Bird is assumed as fluidic in a impact. Generated stresses in the bird body are significant than its yield stresses. Hydrodynamic theory is most ideal for describing this problem. Impactor literally flows steadily over the target for most part of this problem. The impact starts with an initial shock and falls into a radial release shock regime. Subsequently a steady flow is established in the bird body and this phase continues till the whole length of the bird body is turned around. Initial shock pressure and steady state pressure are ideal variables for comparing and validating the bird model. Spatial discretization of the bird is done using Smooth Particle Hydrodynamic (SPH) approach. This Discrete Element Model (DEM) offers significant advantages over other contemporary approaches. Thermodynamic state variable relations are established using Polynomial Equation of State (EOS). ANSYS AUTODYN is used to perform the explicit dynamic simulation of the impact event. Validation of the shock and steady pressure data for different try geometries is done against experimental and other published theoretical results, which yielded a geometry which best reflects the load values as in a real bird impact event.

Combining Computational Methods for Hit to Lead Optimization in Mycobacterium tuberculosis Drug Discovery

PubMed Central

Ekins, Sean; Freundlich, Joel S.; Hobrath, Judith V.; White, E. Lucile; Reynolds, Robert C

2013-01-01

Purpose Tuberculosis treatments need to be shorter and overcome drug resistance. Our previous large scale phenotypic high-throughput screening against Mycobacterium tuberculosis (Mtb) has identified 737 active compounds and thousands that are inactive. We have used this data for building computational models as an approach to minimize the number of compounds tested. Methods A cheminformatics clustering approach followed by Bayesian machine learning models (based on publicly available Mtb screening data) was used to illustrate that application of these models for screening set selections can enrich the hit rate. Results In order to explore chemical diversity around active cluster scaffolds of the dose-response hits obtained from our previous Mtb screens a set of 1924 commercially available molecules have been selected and evaluated for antitubercular activity and cytotoxicity using Vero, THP-1 and HepG2 cell lines with 4.3%, 4.2% and 2.7% hit rates, respectively. We demonstrate that models incorporating antitubercular and cytotoxicity data in Vero cells can significantly enrich the selection of non-toxic actives compared to random selection. Across all cell lines, the Molecular Libraries Small Molecule Repository (MLSMR) and cytotoxicity model identified ~10% of the hits in the top 1% screened (>10 fold enrichment). We also showed that seven out of nine Mtb active compounds from different academic published studies and eight out of eleven Mtb active compounds from a pharmaceutical screen (GSK) would have been identified by these Bayesian models. Conclusion Combining clustering and Bayesian models represents a useful strategy for compound prioritization and hit-to lead optimization of antitubercular agents. PMID:24132686

Time Course of Visual Extrapolation Accuracy

DTIC Science & Technology

1995-09-01

The pond and duckweed problem: Three experiments on the misperception of exponential growth . Acta Psychologica 43, 239-251. Wiener, E.L., 1962...random variation in tracker velocity. Both models predicted changes in hit and false alarm rates well, except in a condition where response asymmetries...systematic velocity error in tracking, only random variation in tracker velocity. Both models predicted changes in hit and false alarm rates well

Statistical Properties and Pre-Hit Dynamics of Price Limit Hits in the Chinese Stock Markets

PubMed Central

Wan, Yu-Lei; Xie, Wen-Jie; Gu, Gao-Feng; Jiang, Zhi-Qiang; Chen, Wei; Xiong, Xiong; Zhang, Wei; Zhou, Wei-Xing

2015-01-01

Price limit trading rules are adopted in some stock markets (especially emerging markets) trying to cool off traders’ short-term trading mania on individual stocks and increase market efficiency. Under such a microstructure, stocks may hit their up-limits and down-limits from time to time. However, the behaviors of price limit hits are not well studied partially due to the fact that main stock markets such as the US markets and most European markets do not set price limits. Here, we perform detailed analyses of the high-frequency data of all A-share common stocks traded on the Shanghai Stock Exchange and the Shenzhen Stock Exchange from 2000 to 2011 to investigate the statistical properties of price limit hits and the dynamical evolution of several important financial variables before stock price hits its limits. We compare the properties of up-limit hits and down-limit hits. We also divide the whole period into three bullish periods and three bearish periods to unveil possible differences during bullish and bearish market states. To uncover the impacts of stock capitalization on price limit hits, we partition all stocks into six portfolios according to their capitalizations on different trading days. We find that the price limit trading rule has a cooling-off effect (object to the magnet effect), indicating that the rule takes effect in the Chinese stock markets. We find that price continuation is much more likely to occur than price reversal on the next trading day after a limit-hitting day, especially for down-limit hits, which has potential practical values for market practitioners. PMID:25874716

Implementation of a rapid HIT immunoassay at a university hospital - Retrospective analysis of HIT laboratory orders in patients with thrombocytopenia.

PubMed

Black, Anne; Heimerl, Susanne; Oertli, Linnéa; Wilczek, Wolf; Greinacher, Andreas; Spannagl, Michael; Herr, Wolfgang; Hart, Christina

2017-10-01

Heparin-induced thrombocytopenia (HIT) is a rare cause of thrombocytopenia and a potentially life-threatening adverse drug reaction. Clinical overdiagnosis of HIT results in costly laboratory tests and anticoagulation. Criteria and algorithms for diagnosis are established, but their translation into clinical practice is still challenging. In a retrospective approach we studied all HIT related laboratory test requests within four years and evaluated data before (1st period, 24month) and after (2nd period, 24month) replacing particle gel immunoassay (PaGIA) and enzyme-linked immunosorbent assay (ELISA) by a chemiluminescent immunoassay (CLIA). HIT was confirmed by heparin-induced platelet activation (HIPA) test. Clinical pretest probability for HIT using an implemented simplified 4Ts score and platelet count were evaluated. Costs for laboratory tests and alternative anticoagulation were calculated. In 1850 patients with suspected HIT, 2327 laboratory orders were performed. In 87.2% of these orders an intermediate/high simplified 4Ts score was found. Thrombocytopenia was present in 87.1%. After replacing PaGIA and ELISA by CLIA the number of immunological and functional laboratory tests was reduced by 38.2%. The number of positive HIT immunoassays declined from 22.6% to 6.0%, while the number of positive HIPA tests among positive immunological tests increased by 19%. Altogether, acute HIT was confirmed in 59 patients. A decline in the use of alternative anticoagulants was observed in the 2nd period. Our study shows that in a university hospital setting HIT is well-known, but diagnosis requires a precise laboratory confirmation. Replacing PaGIA and ELISA by CLIA did not influence laboratory order behavior but results in reduced overall costs for laboratory diagnostics and alternative anticoagulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Estimating residual fault hitting rates by recapture sampling

NASA Technical Reports Server (NTRS)

Lee, Larry; Gupta, Rajan

1988-01-01

For the recapture debugging design introduced by Nayak (1988) the problem of estimating the hitting rates of the faults remaining in the system is considered. In the context of a conditional likelihood, moment estimators are derived and are shown to be asymptotically normal and fully efficient. Fixed sample properties of the moment estimators are compared, through simulation, with those of the conditional maximum likelihood estimators. Properties of the conditional model are investigated such as the asymptotic distribution of linear functions of the fault hitting frequencies and a representation of the full data vector in terms of a sequence of independent random vectors. It is assumed that the residual hitting rates follow a log linear rate model and that the testing process is truncated when the gaps between the detection of new errors exceed a fixed amount of time.

Rationale and Study Protocol for a Multi-component Health Information Technology (HIT) Screening Tool for Depression and Post-traumatic Stress Disorder in the Primary Care Setting

PubMed Central

Biegler, Kelly; Mollica, Richard; Sim, Susan Elliott; Nicholas, Elisa; Chandler, Maria; Ngo-Metzger, Quyen; Paigne, Kittya; Paigne, Sompia; Nguyen, Danh V.; Sorkin, Dara H.

2016-01-01

The prevalence rate of depression in primary care is high. Primary care providers serve as the initial point of contact for the majority of patients with depression, yet, approximately 50% of cases remain unrecognized. The under-diagnosis of depression may be further exacerbated in limited English-language proficient (LEP) populations. Language barriers may result in less discussion of patients’ mental health needs and fewer referrals to mental health services, particularly given competing priorities of other medical conditions and providers’ time pressures. Recent advances in Health Information Technology (HIT) may facilitate novel ways to screen for depression in LEP populations. The purpose of this paper is to describe the rationale and protocol of a clustered-randomized controlled trial that will test the effectiveness of an HIT intervention that provides a multi-component approach to delivering culturally competent, mental health care in the primary care setting. The HIT intervention has four components: 1) web-based provider training, 2) multimedia electronic screening of depression and PTSD in the patients’ primary language, 3) Computer generated risk assessment scores delivered directly to the provider, and 4) clinical decision support. The outcomes of the study include assessing the potential of the HIT intervention to improve screening rates, clinical detection, provider initiation of treatment, and patient outcomes for depression and PTSD among LEP Cambodian refugees who experienced war atrocities and trauma during the Khmer Rouge. This technology has the potential to be adapted to any LEP population in order to facilitate mental health screening and treatment in the primary care setting. PMID:27394385

Rationale and study protocol for a multi-component Health Information Technology (HIT) screening tool for depression and post-traumatic stress disorder in the primary care setting.

PubMed

Biegler, Kelly; Mollica, Richard; Sim, Susan Elliott; Nicholas, Elisa; Chandler, Maria; Ngo-Metzger, Quyen; Paigne, Kittya; Paigne, Sompia; Nguyen, Danh V; Sorkin, Dara H

2016-09-01

The prevalence rate of depression in primary care is high. Primary care providers serve as the initial point of contact for the majority of patients with depression, yet, approximately 50% of cases remain unrecognized. The under-diagnosis of depression may be further exacerbated in limited English-language proficient (LEP) populations. Language barriers may result in less discussion of patients' mental health needs and fewer referrals to mental health services, particularly given competing priorities of other medical conditions and providers' time pressures. Recent advances in Health Information Technology (HIT) may facilitate novel ways to screen for depression and other mental health disorders in LEP populations. The purpose of this paper is to describe the rationale and protocol of a clustered randomized controlled trial that will test the effectiveness of an HIT intervention that provides a multi-component approach to delivering culturally competent, mental health care in the primary care setting. The HIT intervention has four components: 1) web-based provider training, 2) multimedia electronic screening of depression and PTSD in the patients' primary language, 3) Computer generated risk assessment scores delivered directly to the provider, and 4) clinical decision support. The outcomes of the study include assessing the potential of the HIT intervention to improve screening rates, clinical detection, provider initiation of treatment, and patient outcomes for depression and post-traumatic stress disorder (PTSD) among LEP Cambodian refugees who experienced war atrocities and trauma during the Khmer Rouge. This technology has the potential to be adapted to any LEP population in order to facilitate mental health screening and treatment in the primary care setting. Copyright © 2016 Elsevier Inc. All rights reserved.

The hit problem for symmetric polynomials over the Steenrod algebra

NASA Astrophysics Data System (ADS)

Janfada, A. S.; Wood, R. M. W.

2002-09-01

We cite [18] for references to work on the hit problem for the polynomial algebra P(n) = [open face F]2[x1, ;…, xn] = [oplus B: plus sign in circle]d[gt-or-equal, slanted]0 Pd(n), viewed as a graded left module over the Steenrod algebra [script A] at the prime 2. The grading is by the homogeneous polynomials Pd(n) of degree d in the n variables x1, …, xn of grading 1. The present article investigates the hit problem for the [script A]-submodule of symmetric polynomials B(n) = P(n)[sum L: summation operator]n , where [sum L: summation operator]n denotes the symmetric group on n letters acting on the right of P(n). Among the main results is the symmetric version of the well-known Peterson conjecture. For a positive integer d, let [mu](d) denote the smallest value of k for which d = [sum L: summation operator]ki=1(2[lambda]i[minus sign]1), where [lambda]i [gt-or-equal, slanted] 0.

Selection, application, and validation of a set of molecular descriptors for nuclear receptor ligands.

PubMed

Stewart, Eugene L; Brown, Peter J; Bentley, James A; Willson, Timothy M

2004-08-01

A methodology for the selection and validation of nuclear receptor ligand chemical descriptors is described. After descriptors for a targeted chemical space were selected, a virtual screening methodology utilizing this space was formulated for the identification of potential NR ligands from our corporate collection. Using simple descriptors and our virtual screening method, we are able to quickly identify potential NR ligands from a large collection of compounds. As validation of the virtual screening procedure, an 8, 000-membered NR targeted set and a 24, 000-membered diverse control set of compounds were selected from our in-house general screening collection and screened in parallel across a number of orphan NR FRET assays. For the two assays that provided at least one hit per set by the established minimum pEC(50) for activity, the results showed a 2-fold increase in the hit-rate of the targeted compound set over the diverse set.

A novel 3-dimensional electromagnetic guidance system increases intraoperative microwave antenna placement accuracy.

PubMed

Sastry, Amit V; Swet, Jacob H; Murphy, Keith J; Baker, Erin H; Vrochides, Dionisios; Martinie, John B; McKillop, Iain H; Iannitti, David A

2017-12-01

Failure to locate lesions and accurately place microwave antennas can lead to incomplete tumor ablation. The Emprint™ SX Ablation Platform employs real-time 3D-electromagnetic spatial antenna tracking to generate intraoperative laparoscopic antenna guidance. We sought to determine whether Emprint™ SX affected time/accuracy of antenna-placement in a laparoscopic training model. Targets (7-10 mm) were set in agar within a laparoscopic training device. Novices (no surgical experience), intermediates (surgical residents), and experts (HPB-surgeons) were asked to locate and hit targets using a MWA antenna (10-ultrasound only, 10-Emprint™ SX). Time to locate target, number of attempts to hit the target, first-time hit rate, and time from initiating antenna advance to hitting the target were measured. Participants located 100% of targets using ultrasound, with experts taking significantly less time than novices and intermediates. Using ultrasound only, successful hit-rates were 70% for novices and 90% for intermediates and experts. Using Emprint™ SX, successful hit rates for all 3-groups were 100%, with significantly increased first-time hit-rates and reduced time required to hit targets compared to ultrasound only. Emprint™ SX significantly improved accuracy and speed of antenna-placement independent of experience, and was particularly beneficial for novice users. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Modeling Rare Baseball Events--Are They Memoryless?

ERIC Educational Resources Information Center

Huber, Michael; Glen, Andrew

2007-01-01

Three sets of rare baseball events--pitching a no-hit game, hitting for the cycle, and turning a triple play--offer excellent examples of events whose occurrence may be modeled as Poisson processes. That is, the time of occurrence of one of these events doesn't affect when we see the next occurrence of such. We modeled occurrences of these three…

The importance of interaction in the implementation of information technology in health care: a symbolic interactionism study on the meaning of accessibility.

PubMed

Nilsson, Lina; Hofflander, Malin; Eriksén, Sara; Borg, Christel

2012-12-01

A challenge when groups from different disciplines work together in implementing health information technology (HIT) in a health-care context is that words often have different meanings depending upon work practices, and definition of situations. Accessibility is a word commonly associated with HIT implementation. This study aimed to investigate different meanings of accessibility when implementing HIT in everyday work practice in a health-care context. It focused on the perspective of nurses to highlight another view of the complex relationship between HIT and information in a health-care context. This is a qualitative study influenced by institutional ethnographic. District nurses and student nurses were interviewed. The results indicate that when implementing HIT accessibility depends on working routines, social structures and patient relationship. The findings of the study suggest that interaction needs to take on a more important role when implementing HIT because people act upon words from the interpreted meaning of them. Symbolic interactionism is proposed as a way to set a mutual stage to facilitate an overall understanding of the importance of the meaning of words. There is a need for making place and space for negotiation of the meaning of words when implementing HIT in everyday work practice.

Similarity searching and scaffold hopping in synthetically accessible combinatorial chemistry spaces.

PubMed

Boehm, Markus; Wu, Tong-Ying; Claussen, Holger; Lemmen, Christian

2008-04-24

Large collections of combinatorial libraries are an integral element in today's pharmaceutical industry. It is of great interest to perform similarity searches against all virtual compounds that are synthetically accessible by any such library. Here we describe the successful application of a new software tool CoLibri on 358 combinatorial libraries based on validated reaction protocols to create a single chemistry space containing over 10 (12) possible products. Similarity searching with FTrees-FS allows the systematic exploration of this space without the need to enumerate all product structures. The search result is a set of virtual hits which are synthetically accessible by one or more of the existing reaction protocols. Grouping these virtual hits by their synthetic protocols allows the rapid design and synthesis of multiple follow-up libraries. Such library ideas support hit-to-lead design efforts for tasks like follow-up from high-throughput screening hits or scaffold hopping from one hit to another attractive series.

The training and support needs of faculty and students using a health information technology system were significant: a case study in a dental school.

PubMed

Hill, Heather K; Stewart, Denice C L; Ash, Joan S

2010-11-13

Health Information Technology Systems (HITS) are becoming more widely integrated into patient care in the dental school setting. The purpose of this study was to evaluate the impact of a chairside HITS on users in the dental school setting. Qualitative techniques, including interviews, focus groups and observations, were used. Using grounded theory, we saw 9 themes emerge. One theme of particular interest was that "training and support needs of end-users were significant." This paper explores this theme in detail and discusses the implications.

Flight set 360L007 (STS-33R) field joint protection system, thermal protection system, and systems tunnel components, volume 7

NASA Technical Reports Server (NTRS)

1990-01-01

The performance of the thermal protection system, field joint protection system, and systems tunnel components of flight set 360L007 is presented as evaluated by postflight hardware inspection. The condition of both motors was similar to previous flights. Four aft edge strikes were noted on the ground environment instrumentation thermal protection system. The hits all left a clean substrate, indicating that the damage was caused by nozzle severance debris and/or water impact. No National Space Transportation System debris criteria for missing thermal protection system were violated. Two problem reports were written against the field joint protection system. The first concerned two cracks in the K5NA closeout over the trunnion/vent valve location on the left-hand aft field joint. A similar condition was observed on Flight 5 (360H005). The second problem report referred to a number of small surface cracks between two impact marks on the left-hand forward field joint. Neither area exhibited loose material or any abnormal heat effects, and they have no impact on flight safety.

The impact of the heparin-induced thrombocytopenia (HIT) computerized alert on provider behaviors and patient outcomes.

PubMed

Austrian, Jonathan S; Adelman, Jason S; Reissman, Stan H; Cohen, Hillel W; Billett, Henny H

2011-01-01

The aim of this study was to measure the effect of an electronic heparin-induced thrombocytopenia (HIT) alert on provider ordering behaviors and on patient outcomes. A pop-up alert was created for providers when an individual's platelet values had decreased by 50% or to <100,000/mm(3) in the setting of recent heparin exposure. The authors retrospectively compared inpatients admitted between January 24, 2008 and August 24, 2008 to a control group admitted 1 year prior to the HIT alert. The primary outcome was a change in HIT antibody testing. Secondary outcomes included an assessment of incidence of HIT antibody positivity, percentage of patients started on a direct thrombin inhibitor (DTI), length of stay and overall mortality. There were 1006 and 1081 patients in the control and intervention groups, respectively. There was a 33% relative increase in HIT antibody test orders (p=0.01), and 33% more of these tests were ordered the first day after the criteria were met when a pop-up alert was given (p=0.03). Heparin was discontinued in 25% more patients in the alerted group (p=0.01), and more direct thrombin inhibitors were ordered for them (p=0.03). The number who tested HIT antibody-positive did not differ, however, between the two groups (p=0.99). The length of stay and mortality were similar in both groups. The HIT alert significantly impacted provider behaviors. However, the alert did not result in more cases of HIT being detected or an improvement in overall mortality. Our findings do not support implementation of a computerized HIT alert.

Staff Responses When Parents Hit Children in a Hospital Setting.

PubMed

Font, Sarah A; Gershoff, Elizabeth T; Taylor, Catherine A; Terreros, Amy; Nielsen-Parker, Monica; Spector, Lisa; Foster, Rebecca H; Budzak Garza, Ann; Olson-Dorff, Denyse

Physical punishment of children is a prevalent practice that is condemned by most medical professionals given its link with increased risk of child physical abuse and other adverse child outcomes. This study examined the prevalence of parent-to-child hitting in medical settings and the intervention behaviors of staff who witness it. Staff at a children's medical center and a general medical center completed a voluntary, anonymous survey. We used descriptive statistics to examine differences in the experiences of physicians, nurses, and other medical staff. We used logistic regression to predict intervention behaviors among staff who witnessed parent-to-child hitting. Of the hospital staff who completed the survey (N = 2863), we found that 50% of physicians, 24% of nurses, 27% of other direct care staff, and 17% of nondirect care staff witnessed parent-to-child hitting at their medical center in the past year. A majority of physicians, nurses, and other direct care staff reported intervening sometimes or always. Nondirect care staff rarely intervened. Believing staff have the responsibility to intervene, and having comfortable strategies with which to intervene were strongly predictive of intervention behavior. Staff who did not intervene commonly reported that they did not know how to respond. Many medical center staff witness parent-to-child hitting. Although some of the staff reported that they intervened when they witnessed this behavior, the findings indicate that staff may need training to identify when and how they should respond.

The economics of health information technology in medication management: a systematic review of economic evaluations.

PubMed

O'Reilly, Daria; Tarride, Jean-Eric; Goeree, Ron; Lokker, Cynthia; McKibbon, K Ann

2012-01-01

To conduct a systematic review and synthesis of the evidence surrounding the cost-effectiveness of health information technology (HIT) in the medication process. Peer-reviewed electronic databases and gray literature were searched to identify studies on HIT used to assist in the medication management process. Articles including an economic component were reviewed for further screening. For this review, full cost-effectiveness analyses, cost-utility analyses and cost-benefit analyses, as well as cost analyses, were eligible for inclusion and synthesis. The 31 studies included were heterogeneous with respect to the HIT evaluated, setting, and economic methods used. Thus the data could not be synthesized, and a narrative review was conducted. Most studies evaluated computer decision support systems in hospital settings in the USA, and only five of the studied performed full economic evaluations. Most studies merely provided cost data; however, useful economic data involves far more input. A full economic evaluation includes a full enumeration of the costs, synthesized with the outcomes of the intervention. The quality of the economic literature in this area is poor. A few studies found that HIT may offer cost advantages despite their increased acquisition costs. However, given the uncertainty that surrounds the costs and outcomes data, and limited study designs, it is difficult to reach any definitive conclusion as to whether the additional costs and benefits represent value for money. Sophisticated concurrent prospective economic evaluations need to be conducted to address whether HIT interventions in the medication management process are cost-effective.

Staff Responses When Parents Hit Children in a Hospital Setting

PubMed Central

Font, Sarah A.; Gershoff, Elizabeth T.; Taylor, Catherine A.; Terreros, Amy; Nielsen-Parker, Monica; Spector, Lisa; Foster, Rebecca H.; Budzak Garza, Ann; Olson-Dorff, Denyse

2016-01-01

Objective Physical punishment of children is a prevalent practice that is condemned by most medical professionals given its link with increased risk of child physical abuse and other adverse child outcomes. This study examined the prevalence of parent-to-child hitting in medical settings and the intervention behaviors of staff who witness it. Method Staff at a children's medical center and a general medical center completed a voluntary, anonymous survey. We used descriptive statistics to examine differences in the experiences of physicians, nurses, and other medical staff. We used logistic regression to predict intervention behaviors among staff who witnessed parent-to-child hitting. Results Of the hospital staff who completed the survey (N=2,863), we found that 50% of physicians, 24% of nurses, 27% of other direct care staff, and 17% of non-direct care staff witnessed parent-to-child hitting at their medical center in the past year. A majority of physicians, nurses and other direct care staff reported intervening sometimes or always. Non-direct care staff rarely intervened. Believing staff have the responsibility to intervene and having comfortable strategies with which to intervene were strongly predictive of intervention behavior. Staff who did not intervene commonly reported that they did not know how to respond. Conclusion Many medical center staff witness parent-to-child hitting. Although some of the staff reported that they intervened when they witnessed this behavior, the findings indicate that staff may need training to identify when and how they should respond. PMID:27802257

Performance Prediction Toolkit

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

Chennupati, Gopinath; Santhi, Nanadakishore; Eidenbenz, Stephen

The Performance Prediction Toolkit (PPT), is a scalable co-design tool that contains the hardware and middle-ware models, which accept proxy applications as input in runtime prediction. PPT relies on Simian, a parallel discrete event simulation engine in Python or Lua, that uses the process concept, where each computing unit (host, node, core) is a Simian entity. Processes perform their task through message exchanges to remain active, sleep, wake-up, begin and end. The PPT hardware model of a compute core (such as a Haswell core) consists of a set of parameters, such as clock speed, memory hierarchy levels, their respective sizes,more » cache-lines, access times for different cache levels, average cycle counts of ALU operations, etc. These parameters are ideally read off a spec sheet or are learned using regression models learned from hardware counters (PAPI) data. The compute core model offers an API to the software model, a function called time_compute(), which takes as input a tasklist. A tasklist is an unordered set of ALU, and other CPU-type operations (in particular virtual memory loads and stores). The PPT application model mimics the loop structure of the application and replaces the computational kernels with a call to the hardware model's time_compute() function giving tasklists as input that model the compute kernel. A PPT application model thus consists of tasklists representing kernels and the high-er level loop structure that we like to think of as pseudo code. The key challenge for the hardware model's time_compute-function is to translate virtual memory accesses into actual cache hierarchy level hits and misses.PPT also contains another CPU core level hardware model, Analytical Memory Model (AMM). The AMM solves this challenge soundly, where our previous alternatives explicitly include the L1,L2,L3 hit-rates as inputs to the tasklists. Explicit hit-rates inevitably only reflect the application modeler's best guess, perhaps informed by a few small test problems using hardware counters; also, hard-coded hit-rates make the hardware model insensitive to changes in cache sizes. Alternatively, we use reuse distance distributions in the tasklists. In general, reuse profiles require the application modeler to run a very expensive trace analysis on the real code that realistically can be done at best for small examples.« less

HIT: a new approach for hiding multimedia information in text

NASA Astrophysics Data System (ADS)

El-Kwae, Essam A.; Cheng, Li

2002-04-01

A new technique for hiding multimedia data in text, called the Hiding in Text (HIT) technique, is introduced. The HIT technique can transform any type of media represented by a long binary string into innocuous text that follows correct grammatical rules. This technique divides English words into types where each word can appear in any number of types. For each type, there is a dictionary, which maps words to binary codes. Marker types are special types whose words do not repeat in any other type. Each generated sentence must include at least one word from the marker type. In the hiding phase, a binary string is input to the HIT encoding algorithm, which then selects sentence templates at random. The output is a set of English sentences according to the selected templates and the dictionaries of types. In the retrieving phase, the HIT technique uses the position of the marker word to identify the template used to build each sentence. The proposed technique greatly improves the efficiency and the security features of previous solutions. Examples for hiding text and image information in a cover text are given to illustrate the HIT technique.

Partner violence and sexual jealousy in China: a population-based survey.

PubMed

Wang, Tianfu; Parish, William L; Laumann, Edward O; Luo, Ye

2009-07-01

Using data from a nationally representative survey in China, this article examines the prevalence and risk factors for partner violence with a special focus on the important role of sexual jealousy. Among women aged 20 to 49, 7.2% reported that they were hit by their partners in the past year. Comparison shows that the Chinese prevalence is modestly below the overall median for other societies. Net of other factors, jealousy exacerbates hitting for both men and women in a reactive pattern, with the jealous partner getting hit. This suggests a rethinking of the role of sexual jealousy in spousal violence in some social settings.

Partner Violence and Sexual Jealousy in China: A Population-Based Survey

PubMed Central

Wang, Tianfu; Parish, William L.; Laumann, Edward O.; Luo, Ye

2013-01-01

Using data from a nationally representative survey of China, this paper examines the prevalence and risk factors for partner violence with a special focus on the important role of sexual jealousy. Among women age 20–49, 7.2% reported that they were hit by their partner last year. Comparison shows that the Chinese prevalence is modestly below the overall median for other societies. Net of other factors, jealousy exacerbates hitting for both men and women in a reactive pattern, with the jealous partner getting hit. This suggests a rethinking of the role of sexual jealousy in spousal violence in some social settings. PMID:19451317

Adrenal haemorrhage due to heparin-induced thrombocytopenia.

PubMed

Ketha, Siva; Smithedajkul, Patrick; Vella, Adrian; Pruthi, Rajiv; Wysokinski, Waldemar; McBane, Robert

2013-04-01

Adrenal haemorrhage (AH) is a rare but potentially devastating complication of heparin-induced thrombocytopenia (HIT). Neither the prevalence nor the natural history of AH due to HIT are known. The objectives of this study were to identify the spectrum of AH causes, to characterise the frequency of AH due to HIT and determine the natural history of HIT-associated AH. All patients with incident adrenal haemorrhage from January 2002 through June 2012 seen at the Mayo Clinic were identified. Over this time frame, there were a total of 115 patients with AH of which 11 cases (10%; mean age 67 ± 8 years; 73% female) were associated with HIT. Of these, all but one occurred in the postoperative setting and involved both adrenal glands (89%) with acute adrenal insufficiency at the time of diagnosis. Cases were found incidentally during an evaluation for fever, shock, abdominal pain or mental status changes. All HIT patients experienced venous thrombosis at other locations including deep venous thromboses (n=14), pulmonary emboli (n= 4) and arterial thrombosis (n=2). Four patients undergoing total knee arthroplasty had "spontaneous HIT" with AH in the absence of identifiable heparin exposure. Other causes of AH included trauma (29%), sepsis (15%), antiphospholipid antibody syndrome (10%), and metastatic disease (12%). In conclusion, AH is an important but seldom recognised presumed thrombotic complication of HIT, which usually occurs in the postoperative period, especially after orthopaedic procedures. This syndrome can occur in the apparent absence of heparin exposure, especially following major joint replacement surgery.

Parameter Optimization for Feature and Hit Generation in a General Unknown Screening Method-Proof of Concept Study Using a Design of Experiment Approach for a High Resolution Mass Spectrometry Procedure after Data Independent Acquisition.

PubMed

Elmiger, Marco P; Poetzsch, Michael; Steuer, Andrea E; Kraemer, Thomas

2018-03-06

High resolution mass spectrometry and modern data independent acquisition (DIA) methods enable the creation of general unknown screening (GUS) procedures. However, even when DIA is used, its potential is far from being exploited, because often, the untargeted acquisition is followed by a targeted search. Applying an actual GUS (including untargeted screening) produces an immense amount of data that must be dealt with. An optimization of the parameters regulating the feature detection and hit generation algorithms of the data processing software could significantly reduce the amount of unnecessary data and thereby the workload. Design of experiment (DoE) approaches allow a simultaneous optimization of multiple parameters. In a first step, parameters are evaluated (crucial or noncrucial). Second, crucial parameters are optimized. The aim in this study was to reduce the number of hits, without missing analytes. The obtained parameter settings from the optimization were compared to the standard settings by analyzing a test set of blood samples spiked with 22 relevant analytes as well as 62 authentic forensic cases. The optimization lead to a marked reduction of workload (12.3 to 1.1% and 3.8 to 1.1% hits for the test set and the authentic cases, respectively) while simultaneously increasing the identification rate (68.2 to 86.4% and 68.8 to 88.1%, respectively). This proof of concept study emphasizes the great potential of DoE approaches to master the data overload resulting from modern data independent acquisition methods used for general unknown screening procedures by optimizing software parameters.

A Dutch and American commentary on IT in health care: roundtable discussions on IT and innovations in health care.

PubMed

Savage, Grant T; van der Reis, Leo

2012-01-01

This chapter reports on experts' perspectives on health information technology (HIT) and how it may be used to improve health care quality and to lower health care costs. Two roundtables were convened that focused on how to best use HIT to improve the quality of health care while ensuring it is accessible and affordable. Participants drew upon lessons learned in the Netherlands, the United States, and other countries. The first roundtable focused on the use of (1) electronic health records (EHRs) by health care providers, (2) cloud computing for EHRs and health portals for consumers, and (3) data registries and networks for public health surveillance. The second roundtable highlighted (1) the rapid growth of personalized medicine, (2) the corresponding growth and sophistication of bioinformatics and analytics, (3) the increasing presence of mobile HIT, and (4) the disruptive changes in the institutional structures of biomedical research and development. Governmental sponsorship of small pilot projects to solve practicable health system problems would encourage HIT innovation among key stakeholders. However, large-scale HIT solutions developed through small pilot projects--should be pursued through public-private partnerships. At the same time, governments should speed up legislative and regulatory procedures to encourage adoption of cost-effective HIT innovations. Mobile HIT and social media are capable of fostering disease prevention and encouraging personal responsibility for improving or stabilizing chronic diseases. Both health services researchers and policy makers should find this chapter of value since it highlights trends in HIT and addresses how health care quality may be improved while costs are contained.

Statistical mechanical analysis of linear programming relaxation for combinatorial optimization problems

NASA Astrophysics Data System (ADS)

Takabe, Satoshi; Hukushima, Koji

2016-05-01

Typical behavior of the linear programming (LP) problem is studied as a relaxation of the minimum vertex cover (min-VC), a type of integer programming (IP) problem. A lattice-gas model on the Erdös-Rényi random graphs of α -uniform hyperedges is proposed to express both the LP and IP problems of the min-VC in the common statistical mechanical model with a one-parameter family. Statistical mechanical analyses reveal for α =2 that the LP optimal solution is typically equal to that given by the IP below the critical average degree c =e in the thermodynamic limit. The critical threshold for good accuracy of the relaxation extends the mathematical result c =1 and coincides with the replica symmetry-breaking threshold of the IP. The LP relaxation for the minimum hitting sets with α ≥3 , minimum vertex covers on α -uniform random graphs, is also studied. Analytic and numerical results strongly suggest that the LP relaxation fails to estimate optimal values above the critical average degree c =e /(α -1 ) where the replica symmetry is broken.

Statistical mechanical analysis of linear programming relaxation for combinatorial optimization problems.

PubMed

Takabe, Satoshi; Hukushima, Koji

2016-05-01

Typical behavior of the linear programming (LP) problem is studied as a relaxation of the minimum vertex cover (min-VC), a type of integer programming (IP) problem. A lattice-gas model on the Erdös-Rényi random graphs of α-uniform hyperedges is proposed to express both the LP and IP problems of the min-VC in the common statistical mechanical model with a one-parameter family. Statistical mechanical analyses reveal for α=2 that the LP optimal solution is typically equal to that given by the IP below the critical average degree c=e in the thermodynamic limit. The critical threshold for good accuracy of the relaxation extends the mathematical result c=1 and coincides with the replica symmetry-breaking threshold of the IP. The LP relaxation for the minimum hitting sets with α≥3, minimum vertex covers on α-uniform random graphs, is also studied. Analytic and numerical results strongly suggest that the LP relaxation fails to estimate optimal values above the critical average degree c=e/(α-1) where the replica symmetry is broken.

Modeling the Sliding/Falling Ladder Paradox

ERIC Educational Resources Information Center

Fox, William P.; Fox, James B.

2003-01-01

Recently we were presented with an interesting twist to the sliding ladder problem viewed in the related rates section of most calculus textbooks. Our problem concerning a sliding ladder that eventually hits the ground. At first, those attempting this problem fell into the calculus trap using only related rates. Previous work for this problem…

An ecological alternative to Snodgrass & Vanderwart: 360 high quality colour images with norms for seven psycholinguistic variables.

PubMed

Moreno-Martínez, Francisco Javier; Montoro, Pedro R

2012-01-01

This work presents a new set of 360 high quality colour images belonging to 23 semantic subcategories. Two hundred and thirty-six Spanish speakers named the items and also provided data from seven relevant psycholinguistic variables: age of acquisition, familiarity, manipulability, name agreement, typicality and visual complexity. Furthermore, we also present lexical frequency data derived from Internet search hits. Apart from the high number of variables evaluated, knowing that it affects the processing of stimuli, this new set presents important advantages over other similar image corpi: (a) this corpus presents a broad number of subcategories and images; for example, this will permit researchers to select stimuli of appropriate difficulty as required, (e.g., to deal with problems derived from ceiling effects); (b) the fact of using coloured stimuli provides a more realistic, ecologically-valid, representation of real life objects. In sum, this set of stimuli provides a useful tool for research on visual object- and word-processing, both in neurological patients and in healthy controls.

Measuring and improving patient safety through health information technology: The Health IT Safety Framework

PubMed Central

Singh, Hardeep

2016-01-01

Health information technology (health IT) has potential to improve patient safety but its implementation and use has led to unintended consequences and new safety concerns. A key challenge to improving safety in health IT-enabled healthcare systems is to develop valid, feasible strategies to measure safety concerns at the intersection of health IT and patient safety. In response to the fundamental conceptual and methodological gaps related to both defining and measuring health IT-related patient safety, we propose a new framework, the Health IT Safety (HITS) measurement framework, to provide a conceptual foundation for health IT-related patient safety measurement, monitoring, and improvement. The HITS framework follows both Continuous Quality Improvement (CQI) and sociotechnical approaches and calls for new measures and measurement activities to address safety concerns in three related domains: 1) concerns that are unique and specific to technology (e.g., to address unsafe health IT related to unavailable or malfunctioning hardware or software); 2) concerns created by the failure to use health IT appropriately or by misuse of health IT (e.g. to reduce nuisance alerts in the electronic health record (EHR)), and 3) the use of health IT to monitor risks, health care processes and outcomes and identify potential safety concerns before they can harm patients (e.g. use EHR-based algorithms to identify patients at risk for medication errors or care delays). The framework proposes to integrate both retrospective and prospective measurement of HIT safety with an organization's existing clinical risk management and safety programs. It aims to facilitate organizational learning, comprehensive 360 degree assessment of HIT safety that includes vendor involvement, refinement of measurement tools and strategies, and shared responsibility to identify problems and implement solutions. A long term framework goal is to enable rigorous measurement that helps achieve the safety benefits of health IT in real-world clinical settings. PMID:26369894

Meaningful Use of Electronic Health Records: Experiences From the Field and Future Opportunities.

PubMed

Slight, Sarah Patricia; Berner, Eta S; Galanter, William; Huff, Stanley; Lambert, Bruce L; Lannon, Carole; Lehmann, Christoph U; McCourt, Brian J; McNamara, Michael; Menachemi, Nir; Payne, Thomas H; Spooner, S Andrew; Schiff, Gordon D; Wang, Tracy Y; Akincigil, Ayse; Crystal, Stephen; Fortmann, Stephen P; Bates, David W

2015-09-18

With the aim of improving health care processes through health information technology (HIT), the US government has promulgated requirements for "meaningful use" (MU) of electronic health records (EHRs) as a condition for providers receiving financial incentives for the adoption and use of these systems. Considerable uncertainty remains about the impact of these requirements on the effective application of EHR systems. The Agency for Healthcare Research and Quality (AHRQ)-sponsored Centers for Education and Research in Therapeutics (CERTs) critically examined the impact of the MU policy relating to the use of medications and jointly developed recommendations to help inform future HIT policy. We gathered perspectives from a wide range of stakeholders (N=35) who had experience with MU requirements, including academicians, practitioners, and policy makers from different health care organizations including and beyond the CERTs. Specific issues and recommendations were discussed and agreed on as a group. Stakeholders' knowledge and experiences from implementing MU requirements fell into 6 domains: (1) accuracy of medication lists and medication reconciliation, (2) problem list accuracy and the shift in HIT priorities, (3) accuracy of allergy lists and allergy-related standards development, (4) support of safer and effective prescribing for children, (5) considerations for rural communities, and (6) general issues with achieving MU. Standards are needed to better facilitate the exchange of data elements between health care settings. Several organizations felt that their preoccupation with fulfilling MU requirements stifled innovation. Greater emphasis should be placed on local HIT configurations that better address population health care needs. Although MU has stimulated adoption of EHRs, its effects on quality and safety remain uncertain. Stakeholders felt that MU requirements should be more flexible and recognize that integrated models may achieve information-sharing goals in alternate ways. Future certification rules and requirements should enhance EHR functionalities critical for safer prescribing of medications in children.

Database for High Throughput Screening Hits (dHITS): a simple tool to retrieve gene specific phenotypes from systematic screens done in yeast.

PubMed

Chuartzman, Silvia G; Schuldiner, Maya

2018-03-25

In the last decade several collections of Saccharomyces cerevisiae yeast strains have been created. In these collections every gene is modified in a similar manner such as by a deletion or the addition of a protein tag. Such libraries have enabled a diversity of systematic screens, giving rise to large amounts of information regarding gene functions. However, often papers describing such screens focus on a single gene or a small set of genes and all other loci affecting the phenotype of choice ('hits') are only mentioned in tables that are provided as supplementary material and are often hard to retrieve or search. To help unify and make such data accessible, we have created a Database of High Throughput Screening Hits (dHITS). The dHITS database enables information to be obtained about screens in which genes of interest were found as well as the other genes that came up in that screen - all in a readily accessible and downloadable format. The ability to query large lists of genes at the same time provides a platform to easily analyse hits obtained from transcriptional analyses or other screens. We hope that this platform will serve as a tool to facilitate investigation of protein functions to the yeast community. © 2018 The Authors Yeast Published by John Wiley & Sons Ltd.

Connectionism and Compositional Semantics

DTIC Science & Technology

1989-05-01

can use their hidden layers to learn difficult discriminations. such as panty or the Penzias two clumps/three clumps problem, where the output is...sauce." For novel sentences that are similar to the training sentences (e.g., train on "the girl hit the boy," test on -the boy hit the girl "), the...overridden by semantic considerations. as in this example from Wendy Lehnert (personal communicanon): (5) John saw the girl with the telescope in a red

Improving the performance of minimizers and winnowing schemes

PubMed Central

Marçais, Guillaume; Pellow, David; Bork, Daniel; Orenstein, Yaron; Shamir, Ron; Kingsford, Carl

2017-01-01

Abstract Motivation: The minimizers scheme is a method for selecting k-mers from sequences. It is used in many bioinformatics software tools to bin comparable sequences or to sample a sequence in a deterministic fashion at approximately regular intervals, in order to reduce memory consumption and processing time. Although very useful, the minimizers selection procedure has undesirable behaviors (e.g. too many k-mers are selected when processing certain sequences). Some of these problems were already known to the authors of the minimizers technique, and the natural lexicographic ordering of k-mers used by minimizers was recognized as their origin. Many software tools using minimizers employ ad hoc variations of the lexicographic order to alleviate those issues. Results: We provide an in-depth analysis of the effect of k-mer ordering on the performance of the minimizers technique. By using small universal hitting sets (a recently defined concept), we show how to significantly improve the performance of minimizers and avoid some of its worse behaviors. Based on these results, we encourage bioinformatics software developers to use an ordering based on a universal hitting set or, if not possible, a randomized ordering, rather than the lexicographic order. This analysis also settles negatively a conjecture (by Schleimer et al.) on the expected density of minimizers in a random sequence. Availability and Implementation: The software used for this analysis is available on GitHub: https://github.com/gmarcais/minimizers.git. Contact: gmarcais@cs.cmu.edu or carlk@cs.cmu.edu PMID:28881970

Troubled Waters: Navigating Unintended Consequences of Health Information Technology.

PubMed

Lehmann, C U; Séroussi, B; Jaulent, M-C

2016-11-10

To provide an introduction to the 2016 IMIA Yearbook of Medical Informatics by the editors. We present a brief overview of the 2016 special topic "Unintended consequences of Health IT: new problems, new solutions", we review our choice of special topic section editors, and discuss the transitions in the editorial team for next year. This edition of the Yearbook acknowledges the fact that implementation and use of Health Information Technology (HIT) may result in unintended consequences, which may lead to both adverse and sometimes beneficial outcomes. However to date, in the literature, undesired outcomes are emphasized with a focus on the complex causes and the many sources that may generate them. The growing awareness of the importance of HIT's unintended consequences and their increasing documentation reflect a wider acceptance of HIT by users (more use generating more consequences) and and a new type of users (a shift from early adopters to late adopters and laggards), whith great expectations regarding the improvement of care quality through HIT solutions. Different points of view on new problems and new solutions of unintended consequences of Health IT are presented through the keynote paper, survey papers, and the working group contributions. The regular 2016 issue of the IMIA yearbook focuses on new unintended consequences of Health IT - brought on by wider adoption and different types of users as well as solutions to addressing them.

A set of high quality colour images with Spanish norms for seven relevant psycholinguistic variables: the Nombela naming test.

PubMed

Moreno-Martinez, Francisco Javier; Montoro, Pedro R; Laws, Keith R

2011-05-01

This paper presents a new corpus of 140 high quality colour images belonging to 14 subcategories and covering a range of naming difficulty. One hundred and six Spanish speakers named the items and provided data for several psycholinguistic variables: age of acquisition, familiarity, manipulability, name agreement, typicality and visual complexity. Furthermore, we also present lexical frequency data derived internet search hits. Apart from the large number of variables evaluated, these stimuli present an important advantage with respect to other comparable image corpora in so far as naming performance in healthy individuals is less prone to ceiling effect problems. Reliability and validity indexes showed that our items display similar psycholinguistic characteristics to those of other corpora. In sum, this set of ecologically valid stimuli provides a useful tool for scientists engaged in cognitive and neuroscience-based research.

A Two-Hit Model of Autism: Adolescence as the Second Hit

PubMed Central

Picci, Giorgia; Scherf, K. Suzanne

2015-01-01

Adolescence brings dramatic changes in behavior and neural organization. Unfortunately, for some 30% of individuals with autism, there is marked decline in adaptive functioning during adolescence. We propose a two-hit model of autism. First, early perturbations in neural development function as a “first hit” that sets up a neural system that is “built to fail” in the face of a second hit. Second, the confluence of pubertal hormones, neural reorganization, and increasing social demands during adolescence provides the “second hit” that interferes with the ability to transition into adult social roles and levels of adaptive functioning. In support of this model, we review evidence about adolescent-specific neural and behavioral development in autism. We conclude with predictions and recommendations for empirical investigation about several domains in which developmental trajectories for individuals with autism may be uniquely deterred in adolescence. PMID:26609500

The BioPrompt-box: an ontology-based clustering tool for searching in biological databases.

PubMed

Corsi, Claudio; Ferragina, Paolo; Marangoni, Roberto

2007-03-08

High-throughput molecular biology provides new data at an incredible rate, so that the increase in the size of biological databanks is enormous and very rapid. This scenario generates severe problems not only at indexing time, where suitable algorithmic techniques for data indexing and retrieval are required, but also at query time, since a user query may produce such a large set of results that their browsing and "understanding" becomes humanly impractical. This problem is well known to the Web community, where a new generation of Web search engines is being developed, like Vivisimo. These tools organize on-the-fly the results of a user query in a hierarchy of labeled folders that ease their browsing and knowledge extraction. We investigate this approach on biological data, and propose the so called The BioPrompt-boxsoftware system which deploys ontology-driven clustering strategies for making the searching process of biologists more efficient and effective. The BioPrompt-box (Bpb) defines a document as a biological sequence plus its associated meta-data taken from the underneath databank--like references to ontologies or to external databanks, and plain texts as comments of researchers and (title, abstracts or even body of) papers. Bpboffers several tools to customize the search and the clustering process over its indexed documents. The user can search a set of keywords within a specific field of the document schema, or can execute Blastto find documents relative to homologue sequences. In both cases the search task returns a set of documents (hits) which constitute the answer to the user query. Since the number of hits may be large, Bpbclusters them into groups of homogenous content, organized as a hierarchy of labeled clusters. The user can actually choose among several ontology-based hierarchical clustering strategies, each offering a different "view" of the returned hits. Bpbcomputes these views by exploiting the meta-data present within the retrieved documents such as the references to Gene Ontology, the taxonomy lineage, the organism and the keywords. Of course, the approach is flexible enough to leave room for future additions of other meta-information. The ultimate goal of the clustering process is to provide the user with several different readings of the (maybe numerous) query results and show possible hidden correlations among them, thus improving their browsing and understanding. Bpb is a powerful search engine that makes it very easy to perform complex queries over the indexed databanks (currently only UNIPROT is considered). The ontology-based clustering approach is efficient and effective, and could thus be applied successfully to larger databanks, like GenBank or EMBL.

The BioPrompt-box: an ontology-based clustering tool for searching in biological databases

PubMed Central

Corsi, Claudio; Ferragina, Paolo; Marangoni, Roberto

2007-01-01

Background High-throughput molecular biology provides new data at an incredible rate, so that the increase in the size of biological databanks is enormous and very rapid. This scenario generates severe problems not only at indexing time, where suitable algorithmic techniques for data indexing and retrieval are required, but also at query time, since a user query may produce such a large set of results that their browsing and "understanding" becomes humanly impractical. This problem is well known to the Web community, where a new generation of Web search engines is being developed, like Vivisimo. These tools organize on-the-fly the results of a user query in a hierarchy of labeled folders that ease their browsing and knowledge extraction. We investigate this approach on biological data, and propose the so called The BioPrompt-boxsoftware system which deploys ontology-driven clustering strategies for making the searching process of biologists more efficient and effective. Results The BioPrompt-box (Bpb) defines a document as a biological sequence plus its associated meta-data taken from the underneath databank – like references to ontologies or to external databanks, and plain texts as comments of researchers and (title, abstracts or even body of) papers. Bpboffers several tools to customize the search and the clustering process over its indexed documents. The user can search a set of keywords within a specific field of the document schema, or can execute Blastto find documents relative to homologue sequences. In both cases the search task returns a set of documents (hits) which constitute the answer to the user query. Since the number of hits may be large, Bpbclusters them into groups of homogenous content, organized as a hierarchy of labeled clusters. The user can actually choose among several ontology-based hierarchical clustering strategies, each offering a different "view" of the returned hits. Bpbcomputes these views by exploiting the meta-data present within the retrieved documents such as the references to Gene Ontology, the taxonomy lineage, the organism and the keywords. Of course, the approach is flexible enough to leave room for future additions of other meta-information. The ultimate goal of the clustering process is to provide the user with several different readings of the (maybe numerous) query results and show possible hidden correlations among them, thus improving their browsing and understanding. Conclusion Bpb is a powerful search engine that makes it very easy to perform complex queries over the indexed databanks (currently only UNIPROT is considered). The ontology-based clustering approach is efficient and effective, and could thus be applied successfully to larger databanks, like GenBank or EMBL. PMID:17430575

Classifying health information technology patient safety related incidents - an approach used in Wales.

PubMed

Warm, D; Edwards, P

2012-01-01

Interest in the field of patient safety incident reporting and analysis with respect to Health Information Technology (HIT) has been growing over recent years as the development, implementation and reliance on HIT systems becomes ever more prevalent. One of the rationales for capturing patient safety incidents is to learn from failures in the delivery of care and must form part of a feedback loop which also includes analysis; investigation and monitoring. With the advent of new technologies and organizational programs of delivery the emphasis is increasingly upon analyzing HIT incidents. This thematic review had two objectives, to test the applicability of a framework specifically designed to categorize HIT incidents and to review the Welsh incidents as communicated via the national incident reporting system in order to understand their implications for healthcare. The incidents were those reported as IT/ telecommunications failure/ overload. Incidents were searched for within a national reporting system using a standardized search strategy for incidents occurring between 1(st) January 2009 and 31(st) May 2011. 149 incident reports were identified and classified. The majority (77%) of which were machine related (technical problems) such as access problems; computer system down/too slow; display issues; and software malfunctions. A further 10% (n = 15) of incidents were down to human-computer interaction issues and 13% (n = 19) incidents, mainly telephone related, could not be classified using the framework being tested. On the basis of this review of incidents, it is recommended that the framework be expanded to include hardware malfunctions and the wrong record retrieved/missing data associated with a machine output error (as opposed to human error). In terms of the implications for clinical practice, the incidents reviewed highlighted critical issues including the access problems particularly relating to the use of mobile technologies.

Intrusion detection using rough set classification.

PubMed

Zhang, Lian-hua; Zhang, Guan-hua; Zhang, Jie; Bai, Ying-cai

2004-09-01

Recently machine learning-based intrusion detection approaches have been subjected to extensive researches because they can detect both misuse and anomaly. In this paper, rough set classification (RSC), a modern learning algorithm, is used to rank the features extracted for detecting intrusions and generate intrusion detection models. Feature ranking is a very critical step when building the model. RSC performs feature ranking before generating rules, and converts the feature ranking to minimal hitting set problem addressed by using genetic algorithm (GA). This is done in classical approaches using Support Vector Machine (SVM) by executing many iterations, each of which removes one useless feature. Compared with those methods, our method can avoid many iterations. In addition, a hybrid genetic algorithm is proposed to increase the convergence speed and decrease the training time of RSC. The models generated by RSC take the form of "IF-THEN" rules, which have the advantage of explication. Tests and comparison of RSC with SVM on DARPA benchmark data showed that for Probe and DoS attacks both RSC and SVM yielded highly accurate results (greater than 99% accuracy on testing set).

The economics of health information technology in medication management: a systematic review of economic evaluations

PubMed Central

Tarride, Jean-Eric; Goeree, Ron; Lokker, Cynthia; McKibbon, K Ann

2011-01-01

Objective To conduct a systematic review and synthesis of the evidence surrounding the cost-effectiveness of health information technology (HIT) in the medication process. Materials and methods Peer-reviewed electronic databases and gray literature were searched to identify studies on HIT used to assist in the medication management process. Articles including an economic component were reviewed for further screening. For this review, full cost-effectiveness analyses, cost-utility analyses and cost-benefit analyses, as well as cost analyses, were eligible for inclusion and synthesis. Results The 31 studies included were heterogeneous with respect to the HIT evaluated, setting, and economic methods used. Thus the data could not be synthesized, and a narrative review was conducted. Most studies evaluated computer decision support systems in hospital settings in the USA, and only five of the studied performed full economic evaluations. Discussion Most studies merely provided cost data; however, useful economic data involves far more input. A full economic evaluation includes a full enumeration of the costs, synthesized with the outcomes of the intervention. Conclusion The quality of the economic literature in this area is poor. A few studies found that HIT may offer cost advantages despite their increased acquisition costs. However, given the uncertainty that surrounds the costs and outcomes data, and limited study designs, it is difficult to reach any definitive conclusion as to whether the additional costs and benefits represent value for money. Sophisticated concurrent prospective economic evaluations need to be conducted to address whether HIT interventions in the medication management process are cost-effective. PMID:21984590

Interolog interfaces in protein–protein docking

PubMed Central

Alsop, James D.

2015-01-01

ABSTRACT Proteins are essential elements of biological systems, and their function typically relies on their ability to successfully bind to specific partners. Recently, an emphasis of study into protein interactions has been on hot spots, or residues in the binding interface that make a significant contribution to the binding energetics. In this study, we investigate how conservation of hot spots can be used to guide docking prediction. We show that the use of evolutionary data combined with hot spot prediction highlights near‐native structures across a range of benchmark examples. Our approach explores various strategies for using hot spots and evolutionary data to score protein complexes, using both absolute and chemical definitions of conservation along with refinements to these strategies that look at windowed conservation and filtering to ensure a minimum number of hot spots in each binding partner. Finally, structure‐based models of orthologs were generated for comparison with sequence‐based scoring. Using two data sets of 22 and 85 examples, a high rate of top 10 and top 1 predictions are observed, with up to 82% of examples returning a top 10 hit and 35% returning top 1 hit depending on the data set and strategy applied; upon inclusion of the native structure among the decoys, up to 55% of examples yielded a top 1 hit. The 20 common examples between data sets show that more carefully curated interolog data yields better predictions, particularly in achieving top 1 hits. Proteins 2015; 83:1940–1946. © 2015 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc. PMID:25740680

The effect of road and environmental characteristics on pedestrian hit-and-run accidents in Ghana.

PubMed

Aidoo, Eric Nimako; Amoh-Gyimah, Richard; Ackaah, Williams

2013-04-01

The number of pedestrians who have died as a result of being hit by vehicles has increased in recent years, in addition to vehicle passenger deaths. Many pedestrians who were involved in road traffic accident died as a result of the driver leaving the pedestrian who was struck unattended at the scene of the accident. This paper seeks to determine the effect of road and environmental characteristics on pedestrian hit-and-run accidents in Ghana. Using pedestrian accident data extracted from the National Road Traffic Accident Database at the Building and Road Research Institute (BRRI) of the Council for Scientific and Industrial Research (CSIR), Ghana, a binary logit model was employed in the analysis. The results from the estimated model indicate that fatal accidents, unclear weather, nighttime conditions, and straight and flat road sections without medians and junctions significantly increase the likelihood that the vehicle driver will leave the scene after hitting a pedestrian. Thus, integrating median separation and speed humps into road design and construction and installing street lights will help to curb the problem of pedestrian hit-and-run accidents in Ghana. Copyright © 2012 Elsevier Ltd. All rights reserved.

Patterns of Hits to the Nearshore from a Major Fairway in the Gulf of Finland

NASA Astrophysics Data System (ADS)

Viikmae, B.; Soomere, T.

2012-04-01

The Baltic Sea hosts one of the heaviest ship traffic in the world. Although relatively small in size, still up to 15% of the world's cargo is transported along its numerous fairways. The largest threat to the environment is oil transportation that has increased more than by a factor of two in 2000-2008 and a 40% increase is expected by the year 2015. One of the major marine highways in the European waters enters the Baltic Sea through the Danish Straits, crosses the Baltic Proper and stretches through the Gulf of Finland to Saint Petersburg. An area that is highly vulnerable to ship pollution is the nearshore that usually has the largest ecological value. While the probability of coastal pollution for open ocean coasts can be reduced by shifting ship routes farther offshore, the problem for narrow bays, like the Gulf of Finland, is how to minimize the probability of hitting any of the coasts. To a certain extent, light can be shed to this problem by means of quantification of the offshore areas in terms of their ability to serve a danger to coastal environment if pollution would happen in these areas. A convenient way to address this problem is to use statistical analysis of a large number of Lagrangian trajectories of test particles representing the potential pollution and passively carried by surface currents. In this paper, we make and attempt to quantify the link between potential sources of pollution along an existing fairway and the sections of the coast reached by current-driven pollution. The problem is analysed by means of considering hits to the nearshore from a major fairway in the Gulf of Finland and by making sure whether certain parts of the coast are hit by pollution particles most frequently and whether or not these pollution particles stem from certain specific parts of the fairway. Trajectories are simulated in the Gulf of Finland by placing tracers among a line that follows one of the major fairways from the Baltic Proper to Saint Petersburg. The probabilities for the hit to different parts of the nearshore and the ability of different sections of the fairway to provide coastal pollution have extensive seasonal variability. The potential impact of the fairway is roughly proportional to its distance from the nearest coast. A short section of the fairway to the south of Vyborg and a segment to the west of Tallinn are the most probable sources of coastal pollution. The most frequently hit coastal areas are short fragments between Hanko and Helsinki, the NE coast of the gulf to the south of Vyborg, and longer segments from Tallinn to Hiiumaa on the southern coast of the gulf.

Hit-to-lead evaluation of a novel class of sphingosine 1-phosphate lyase inhibitors.

PubMed

Dinges, Jurgen; Harris, Christopher M; Wallace, Grier A; Argiriadi, Maria A; Queeney, Kara L; Perron, Denise C; Dominguez, Eric; Kebede, Tegest; Desino, Kelly E; Patel, Hetal; Vasudevan, Anil

2016-05-01

Inhibition of sphingosine-1-phosphate lyase has recently been proposed as a potential treatment option for inflammatory disorders such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. In this report we describe our hit-to-lead evaluation of the isoxazolecarboxamide 6, a high-throughput screening hit (in vitro IC50=1.0 μM, cell IC50=1.8 μM), as a novel S1P lyase inhibitor. We were able to establish basic structure-activity relationships around 6 and succeeded in obtaining X-ray structural information which enabled structure-based design. With the discovery of 28, enzyme activity was quickly improved to IC50=120 nM and cell potency to IC50=230 nM. The main liability in the established isoxazolecarboxamide hit series was determined to be metabolic stability. In particular we identified that future lead-optimization efforts to overcome this problem should focus on blocking the N-dealkylation on the secondary amine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rotating Modulation Imager for the Orphan Source Search Problem

DTIC Science & Technology

2008-01-01

black mask. If the photon hits an open element it is transmitted and the function M(x) = 1. If the photon hits a closed mask element it is not...photon enters the top mask pair in the third slit, but passes through the second slit on the bottom mask. With a single black mask this is physically...modulation efficiency changes as a function of mask thickness for both tungsten and lead masks. The black line shows how the field of view changes with

Medical tongue piercing – development and evaluation of a surgical protocol and the perception of procedural discomfort of the participants

PubMed Central

2014-01-01

Background A system providing disabled persons with control of various assistive devices with the tongue has been developed at Aalborg University in Denmark. The system requires an activation unit attached to the tongue with a small piercing. The aim of this study was to establish and evaluate a safe and tolerable procedure for medical tongue piercing and to evaluate the expected and perceived procedural discomfort. Methods Four tetraplegic subjects volunteered for the study. A surgical protocol for a safe insertion of a tongue barbell piercing was presented using sterilized instruments and piercing parts. Moreover, post-procedural observations of participant complications such as bleeding, edema, and infection were recorded. Finally, procedural discomforts were monitored by VAS scores of pain, changes in taste and speech as well as problems related to hitting the teeth. Results The piercings were all successfully inserted in less than 5 min and the pain level was moderate compared with oral injections. No bleeding, infection, embedding of the piercing, or tooth/gingival injuries were encountered; a moderate edema was found in one case without affecting the speech. In two cases the piercing rod later had to be replaced by a shorter rod, because participants complained that the rod hit their teeth. The replacements prevented further problems. Moreover, loosening of balls was encountered, which could be prevented with the addition of dental glue. No cases of swallowing or aspiration of the piercing parts were recorded. Conclusions The procedure proved simple, fast, and safe for insertion of tongue piercings for tetraplegic subjects in a clinical setting. The procedure represented several precautions in order to avoid risks in these susceptible participants with possible co-morbidity. No serious complications were encountered, and the procedure was found tolerable to the participants. The procedure may be used in future studies with tongue piercings being a prerequisite for similar systems, and this may include insertion in an out-patient setting. PMID:24684776

Identification of ligand efficient, fragment-like hits from an HTS library: structure-based virtual screening and docking investigations of 2H- and 3H-pyrazolo tautomers for Aurora kinase A selectivity.

PubMed

Sarvagalla, Sailu; Singh, Vivek Kumar; Ke, Yi-Yu; Shiao, Hui-Yi; Lin, Wen-Hsing; Hsieh, Hsing-Pang; Hsu, John T A; Coumar, Mohane Selvaraj

2015-01-01

Furanopyrimidine 1 (IC50 = 273 nM, LE = 0.36, LELP = 10.28) was recently identified by high-throughput screening (HTS) of an in-house library (125,000 compounds) as an Aurora kinase inhibitor. Structure-based hit optimization resulted in lead molecules with in vivo efficacy in a mouse tumour xenograft model, but no oral bioavailability. This is attributed to "molecular obesity", a common problem during hit to lead evolution during which degradation of important molecular properties such as molecular weight (MW) and lipophilicity occurs. This could be effectively tackled by the right choice of hit compounds for optimization. In this regard, ligand efficiency (LE) and ligand efficiency dependent lipophilicity (LELP) indices are more often used to choose fragment-like hits for optimization. To identify hits with appropriate LE, we used a MW cut-off <250, and pyrazole structure to filter HTS library. Next, structure-based virtual screening using software (Libdock and Glide) in the Aurora A crystal structure (PDB ID: 3E5A) was carried out, and the top scoring 18 compounds tested for Aurora A enzyme inhibition. This resulted in the identification of a novel tetrahydro-pyrazolo-isoquinoline hit 7 (IC50 = 852 nM, LE = 0.44, LELP = 8.36) with fragment-like properties suitable for further hit optimization. Moreover, hit 7 was found to be selective for Aurora A (Aurora B IC50 = 35,150 nM) and the possible reasons for selectivity investigated by docking two tautomeric forms (2H- and 3H-pyrazole) of 7 in Auroras A and B (PDB ID: 4AF3) crystal structures. This docking study shows that the major 3H-pyrazole tautomer of 7 binds in Aurora A stronger than in Aurora B.

Identification of ligand efficient, fragment-like hits from an HTS library: structure-based virtual screening and docking investigations of 2 H- and 3 H-pyrazolo tautomers for Aurora kinase A selectivity

NASA Astrophysics Data System (ADS)

Sarvagalla, Sailu; Singh, Vivek Kumar; Ke, Yi-Yu; Shiao, Hui-Yi; Lin, Wen-Hsing; Hsieh, Hsing-Pang; Hsu, John T. A.; Coumar, Mohane Selvaraj

2015-01-01

Furanopyrimidine 1 (IC50 = 273 nM, LE = 0.36, LELP = 10.28) was recently identified by high-throughput screening (HTS) of an in-house library (125,000 compounds) as an Aurora kinase inhibitor. Structure-based hit optimization resulted in lead molecules with in vivo efficacy in a mouse tumour xenograft model, but no oral bioavailability. This is attributed to "molecular obesity", a common problem during hit to lead evolution during which degradation of important molecular properties such as molecular weight (MW) and lipophilicity occurs. This could be effectively tackled by the right choice of hit compounds for optimization. In this regard, ligand efficiency (LE) and ligand efficiency dependent lipophilicity (LELP) indices are more often used to choose fragment-like hits for optimization. To identify hits with appropriate LE, we used a MW cut-off <250, and pyrazole structure to filter HTS library. Next, structure-based virtual screening using software (Libdock and Glide) in the Aurora A crystal structure (PDB ID: 3E5A) was carried out, and the top scoring 18 compounds tested for Aurora A enzyme inhibition. This resulted in the identification of a novel tetrahydro-pyrazolo-isoquinoline hit 7 (IC50 = 852 nM, LE = 0.44, LELP = 8.36) with fragment-like properties suitable for further hit optimization. Moreover, hit 7 was found to be selective for Aurora A (Aurora B IC50 = 35,150 nM) and the possible reasons for selectivity investigated by docking two tautomeric forms (2 H- and 3 H-pyrazole) of 7 in Auroras A and B (PDB ID: 4AF3) crystal structures. This docking study shows that the major 3 H-pyrazole tautomer of 7 binds in Aurora A stronger than in Aurora B.

QMRA for Drinking Water: 1. Revisiting the Mathematical Structure of Single-Hit Dose-Response Models.

PubMed

Nilsen, Vegard; Wyller, John

2016-01-01

Dose-response models are essential to quantitative microbial risk assessment (QMRA), providing a link between levels of human exposure to pathogens and the probability of negative health outcomes. In drinking water studies, the class of semi-mechanistic models known as single-hit models, such as the exponential and the exact beta-Poisson, has seen widespread use. In this work, an attempt is made to carefully develop the general mathematical single-hit framework while explicitly accounting for variation in (1) host susceptibility and (2) pathogen infectivity. This allows a precise interpretation of the so-called single-hit probability and precise identification of a set of statistical independence assumptions that are sufficient to arrive at single-hit models. Further analysis of the model framework is facilitated by formulating the single-hit models compactly using probability generating and moment generating functions. Among the more practically relevant conclusions drawn are: (1) for any dose distribution, variation in host susceptibility always reduces the single-hit risk compared to a constant host susceptibility (assuming equal mean susceptibilities), (2) the model-consistent representation of complete host immunity is formally demonstrated to be a simple scaling of the response, (3) the model-consistent expression for the total risk from repeated exposures deviates (gives lower risk) from the conventional expression used in applications, and (4) a model-consistent expression for the mean per-exposure dose that produces the correct total risk from repeated exposures is developed. © 2016 Society for Risk Analysis.

Idea Bank: Wiffle Ball Physics

ERIC Educational Resources Information Center

Lancor, Rachael

2009-01-01

Projectile motion, a cornerstone topic of introductory physics, is usually a student's first exposure to the problem-solving techniques used in this subject. Often, this is an inactive learning experience--students work with pencil and paper to read and solve projectile motion problems (e.g., diagrams and descriptions of balls being hit, kicked,…

Comparison of Document Index Graph Using TextRank and HITS Weighting Method in Automatic Text Summarization

NASA Astrophysics Data System (ADS)

Hadyan, Fadhlil; Shaufiah; Arif Bijaksana, Moch.

2017-01-01

Automatic summarization is a system that can help someone to take the core information of a long text instantly. The system can help by summarizing text automatically. there’s Already many summarization systems that have been developed at this time but there are still many problems in those system. In this final task proposed summarization method using document index graph. This method utilizes the PageRank and HITS formula used to assess the web page, adapted to make an assessment of words in the sentences in a text document. The expected outcome of this final task is a system that can do summarization of a single document, by utilizing document index graph with TextRank and HITS to improve the quality of the summary results automatically.

Ligand- and structure-based in silico studies to identify kinesin spindle protein (KSP) inhibitors as potential anticancer agents.

PubMed

Balakumar, Chandrasekaran; Ramesh, Muthusamy; Tham, Chuin Lean; Khathi, Samukelisiwe Pretty; Kozielski, Frank; Srinivasulu, Cherukupalli; Hampannavar, Girish A; Sayyad, Nisar; Soliman, Mahmoud E; Karpoormath, Rajshekhar

2017-11-29

Kinesin spindle protein (KSP) belongs to the kinesin superfamily of microtubule-based motor proteins. KSP is responsible for the establishment of the bipolar mitotic spindle which mediates cell division. Inhibition of KSP expedites the blockade of the normal cell cycle during mitosis through the generation of monoastral MT arrays that finally cause apoptotic cell death. As KSP is highly expressed in proliferating/cancer cells, it has gained considerable attention as a potential drug target for cancer chemotherapy. Therefore, this study envisaged to design novel KSP inhibitors by employing computational techniques/tools such as pharmacophore modelling, virtual database screening, molecular docking and molecular dynamics. Initially, the pharmacophore models were generated from the data-set of highly potent KSP inhibitors and the pharmacophore models were validated against in house test set ligands. The validated pharmacophore model was then taken for database screening (Maybridge and ChemBridge) to yield hits, which were further filtered for their drug-likeliness. The potential hits retrieved from virtual database screening were docked using CDOCKER to identify the ligand binding landscape. The top-ranked hits obtained from molecular docking were progressed to molecular dynamics (AMBER) simulations to deduce the ligand binding affinity. This study identified MB-41570 and CB-10358 as potential hits and evaluated these experimentally using in vitro KSP ATPase inhibition assays.

The Anatomy of a Pitch: Doing Physics with PITCHf/x Data

NASA Astrophysics Data System (ADS)

Kagan, David

2009-10-01

On Aug. 7, 2007, Barry Bonds of the San Francisco Giants was at bat waiting for a 3-2 pitch from Mike Bacsik of the Washington Nationals. The ball left the pitcher's hand at 84.7 mph and arrived at home plate traveling 77.2 mph. It was within 0.2 in of the center of home plate and 3.213 ft above the ground when Bonds swung and hit his 756th home run, making him the all-time leader for homers in a career. Thanks to a company called Sportvision and Major League Baseball, you can get kinematic data on any pitch thrown. Just think of the interesting and realistic physics problems you can generate from such a rich data set!

High Throughput Screening of Esterases, Lipases and Phospholipases in Mutant and Metagenomic Libraries: A Review.

PubMed

Peña-García, Carlina; Martínez-Martínez, Mónica; Reyes-Duarte, Dolores; Ferrer, Manuel

2016-01-01

Nowadays, enzymes can be efficiently identified and screened from metagenomic resources or mutant libraries. A set of a few hundred new enzymes can be found using a simple substrate within few months. Hence, the establishment of collections of enzymes is no longer a big hurdle. However, a key problem is the relatively low rate of positive hits and that a timeline of several years from the identification of a gene to the development of a process is the reality rather than the exception. Major problems are related to the time-consuming and cost-intensive screening process that only very few enzymes finally pass. Accessing to the highest possible enzyme and mutant diversity by different, but complementary approaches is increasingly important. The aim of this review is to deliver state-of-art status of traditional and novel screening protocols for targeting lipases, esterases and phospholipases of industrial relevance, and that can be applied at high throughput scale (HTS) for at least 200 distinct substrates, at a speed of more than 105 - 108 clones/day. We also review fine-tuning sequence analysis pipelines and in silico tools, which can further improve enzyme selection by an unprecedent speed (up to 1030 enzymes). If the hit rate in an enzyme collection could be increased by HTS approaches, it can be expected that also the very further expensive and time-consuming enzyme optimization phase could be significantly shortened, as the processes of enzyme-candidate selection by such methods can be adapted to conditions most likely similar to the ones needed at industrial scale.

A Generalized QMRA Beta-Poisson Dose-Response Model.

PubMed

Xie, Gang; Roiko, Anne; Stratton, Helen; Lemckert, Charles; Dunn, Peter K; Mengersen, Kerrie

2016-10-01

Quantitative microbial risk assessment (QMRA) is widely accepted for characterizing the microbial risks associated with food, water, and wastewater. Single-hit dose-response models are the most commonly used dose-response models in QMRA. Denoting PI(d) as the probability of infection at a given mean dose d, a three-parameter generalized QMRA beta-Poisson dose-response model, PI(d|α,β,r*), is proposed in which the minimum number of organisms required for causing infection, K min , is not fixed, but a random variable following a geometric distribution with parameter 0

Cerebellar Disorders

MedlinePlus

... hit a tennis ball you are activating the cerebellum. The cerebellum is the area of the brain that controls coordination and balance. Problems with the cerebellum include Cancer Genetic disorders Ataxias - failure of muscle ...

Snags hit tethered satellite mission

NASA Technical Reports Server (NTRS)

Schuiling, Roelof

1993-01-01

The processing and course of the STS-46 Space Shuttle Atlantis mission are described. Problems experienced by the astronaut team in deploying the Tethered Satellite System during the mission are recounted.

The Use of Autonomic Modulation Device to Control Training Performance after High-Intensity Interval Training Program.

PubMed

Clemente-Suárez, Vicente Javier; Arroyo-Toledo, Juan Jaime

2018-01-25

The aim of the present research was to analyze the autonomic response in a group of trained swimmers before and after conducting a 4-week period of high-intensity interval training (HIT). Heart rate variability was analyzed in 14 swimmers (16.2 ± 2.6 years, 169.1 ± 10.2 cm and 61.3 ± 9.9 kg) in basal condition and during a HIT session before and after completing a training period. The HIT session that was evaluated consisted of: 16 × 25 m maximum speed, resting 30 s between sets. Participants combined aerobic training with tethered swimming and HIT sessions three times per week in a period of 4 weeks. Results showed a significantly decrease (p < 0.05) of the standard deviation of the NN intervals (SDNN), the standard deviation of differences between adjacent NN intervals (SDSD), the number of successive difference of intervals which differ by more than 50 ms (NN50), after the training period. Results showed a higher parasympathetic activation besides improvements in autonomic adaptation after HIT training period.

Fondaparinux for intra and perioperative anticoagulation in patients with heparin-induced thrombocytopenia candidates for peripheral vascular surgery: Report of 4 cases.

PubMed

Illuminati, Giulio; Calio', Francesco G; Pizzardi, Giulia; Amatucci, Chiara; Masci, Federica; Palumbo, Piergaspare

2016-01-01

Intra and perioperative anticoagulation in patients with heparin induced thrombocytopenia (HIT), candidates for peripheral vascular surgery remains a challenge, as the best alternative to heparin has not yet been established. We evaluated the off-label use of fondaparinux in four patients with HIT, undergoing peripheral vascular surgery procedures. Four patients of whom 3 men of a mean age of 66 years, with proven heparin induced thrombocytopenia (HIT) underwent two axillo-femoral bypasses, one femoro-popliteal bypass and one resection of a splenic artery aneurysm under fondaparinux. No intra or perioperative bleeding or thrombosis of new onset was observed. In the absence of a valid alternative to heparin for intra and perioperative anticoagulation in HIT, several other anticoagulants can be used in an off-label setting. However, no general consensus exist on which should be the one of choice. In this small series fondaparinux appeared to be both safe and effective. These preliminary results seem to justify the off-label use of fondaparinux for intra and perioperative anticoagulation in patients with HIT, candidates for peripheral vascular surgery interventions. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Hit Dexter: A Machine-Learning Model for the Prediction of Frequent Hitters.

PubMed

Stork, Conrad; Wagner, Johannes; Friedrich, Nils-Ole; de Bruyn Kops, Christina; Šícho, Martin; Kirchmair, Johannes

2018-03-20

False-positive assay readouts caused by badly behaving compounds-frequent hitters, pan-assay interference compounds (PAINS), aggregators, and others-continue to pose a major challenge to experimental screening. There are only a few in silico methods that allow the prediction of such problematic compounds. We report the development of Hit Dexter, two extremely randomized trees classifiers for the prediction of compounds likely to trigger positive assay readouts either by true promiscuity or by assay interference. The models were trained on a well-prepared dataset extracted from the PubChem Bioassay database, consisting of approximately 311 000 compounds tested for activity on at least 50 proteins. Hit Dexter reached MCC and AUC values of up to 0.67 and 0.96 on an independent test set, respectively. The models are expected to be of high value, in particular to medicinal chemists and biochemists who can use Hit Dexter to identify compounds for which extra caution should be exercised with positive assay readouts. Hit Dexter is available as a free web service at http://hitdexter.zbh. uni-hamburg.de. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

New oral anticoagulants in the treatment of heparin-induced thrombocytopenia.

PubMed

Sharifi, Mohsen; Bay, Curt; Vajo, Zoltan; Freeman, Wilbur; Sharifi, Mirali; Schwartz, Frederic

2015-04-01

Heparin induced thrombocytopenia (HIT) is a potentially catastrophic syndrome with a high incidence of vascular thrombosis. There are little data on the efficacy of new oral anticoagulants (NOAC) in this setting. This study reports on the outcome of patients with HIT, treated with NOAC. We retrospectively identified 22 patients with HIT who were treated by our group with a combination of NOAC and a short course of argatroban. These patients were evaluated in a prospective fashion for development of outcomes at a mean follow up of 19±3 months. There were a total of 5 deep and 2 superficial vein thromboses diagnosed at index hospitalization. No patient developed arterial thrombosis. All patients tolerated NOAC and their platelet count normalized before discharge. At 19 months of follow-up, 6 patients had died of non-thrombotic causes. There was no bleeding, limb loss or recurrent venous thromboembolism in any patient. In patients with HIT, a short course of parenteral treatment with argatroban followed by administration of a NOAC is highly safe and effective in prevention of thrombosis and normalization of platelet count. Development of HIT however, portends a poor prognosis independent of vascular thrombosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Introducing Bayesian thinking to high-throughput screening for false-negative rate estimation.

PubMed

Wei, Xin; Gao, Lin; Zhang, Xiaolei; Qian, Hong; Rowan, Karen; Mark, David; Peng, Zhengwei; Huang, Kuo-Sen

2013-10-01

High-throughput screening (HTS) has been widely used to identify active compounds (hits) that bind to biological targets. Because of cost concerns, the comprehensive screening of millions of compounds is typically conducted without replication. Real hits that fail to exhibit measurable activity in the primary screen due to random experimental errors will be lost as false-negatives. Conceivably, the projected false-negative rate is a parameter that reflects screening quality. Furthermore, it can be used to guide the selection of optimal numbers of compounds for hit confirmation. Therefore, a method that predicts false-negative rates from the primary screening data is extremely valuable. In this article, we describe the implementation of a pilot screen on a representative fraction (1%) of the screening library in order to obtain information about assay variability as well as a preliminary hit activity distribution profile. Using this training data set, we then developed an algorithm based on Bayesian logic and Monte Carlo simulation to estimate the number of true active compounds and potential missed hits from the full library screen. We have applied this strategy to five screening projects. The results demonstrate that this method produces useful predictions on the numbers of false negatives.

Biotin-c10-AppCH2ppA is an effective new chemical proteomics probe for diadenosine polyphosphate binding proteins.

PubMed

Azhar, M Ameruddin; Wright, Michael; Kamal, Ahmed; Nagy, Judith; Miller, Andrew D

2014-07-01

Here we report on the synthesis of a synthetic, stable biotin-c10-AppCH2ppA conjugate involving an unusual Cannizzaro reaction step. This conjugate is used to bind prospective Ap4A binding proteins from Escherichia coli bacterial cell lyzates. Following binding, identities of these proteins are then determined smoothly by a process of magnetic bio-panning and electrospray mass spectrometry. Protein hits appear to be a definitive set of stress protein related targets. While this hit list may not be exclusive, and may vary with the nature of sampling conditions and organism status, nevertheless hits do appear to correspond with bona fide Ap4A-binding proteins. Therefore these hits represent a sound basis on which to construct new hypotheses concerning the cellular importance of Ap4A to bacterial cells and the potential biological significance of Ap4A-protein binding interactions. Copyright © 2014. Published by Elsevier Ltd.

Novel hits for acetylcholinesterase inhibition derived by docking-based screening on ZINC database.

PubMed

Doytchinova, Irini; Atanasova, Mariyana; Valkova, Iva; Stavrakov, Georgi; Philipova, Irena; Zhivkova, Zvetanka; Zheleva-Dimitrova, Dimitrina; Konstantinov, Spiro; Dimitrov, Ivan

2018-12-01

The inhibition of the enzyme acetylcholinesterase (AChE) increases the levels of the neurotransmitter acetylcholine and symptomatically improves the affected cognitive function. In the present study, we searched for novel AChE inhibitors by docking-based virtual screening of the standard lead-like set of ZINC database containing more than 6 million small molecules using GOLD software. The top 10 best-scored hits were tested in vitro for AChE affinity, neurotoxicity, GIT and BBB permeability. The main pharmacokinetic parameters like volume of distribution, free fraction in plasma, total clearance, and half-life were predicted by previously derived models. Nine of the compounds bind to the enzyme with affinities from 0.517 to 0.735 µM, eight of them are non-toxic. All hits permeate GIT and BBB and bind extensively to plasma proteins. Most of them are low-clearance compounds. In total, seven of the 10 hits are promising for further lead optimisation. These are structures with ZINC IDs: 00220177, 44455618, 66142300, 71804814, 72065926, 96007907, and 97159977.

Health Information Technology Evaluation Framework (HITREF) Comprehensiveness as Assessed in Electronic Point-of-Care Documentation Systems Evaluations.

PubMed

Sockolow, Paulina S; Bowles, Kathryn H; Rogers, Michelle

2015-01-01

We assessed the Health Information Technology (HIT) Reference-based Evaluation Framework (HITREF) comprehensiveness in two HIT evaluations in settings different from that in which the HITREF was developed. Clinician satisfaction themes that emerged from clinician interviews in the home care and the hospital studies were compared to the framework components. Across both studies, respondents commented on 12 of the 20 HITREF components within 5 of the 6 HITREF concepts. No new components emerged that were missing from the HITREF providing evidence that the HITREF is a comprehensive framework. HITREF use in a range of HIT evaluations by researchers new to the HITREF demonstrates that it can be used as intended. Therefore, we continue to recommend the HITREF as a comprehensive, research-based HIT evaluation framework to increase the capacity of informatics evaluators' use of best practice and evidence-based practice to support the credibility of their findings for fulfilling the purpose of program evaluation.

Capture orbits around asteroids by hitting zero-velocity curves

NASA Astrophysics Data System (ADS)

Wang, Wei; Yang, Hongwei; Zhang, Wei; Ma, Guangfu

2017-12-01

The problem of capturing a spacecraft from a heliocentric orbit into a high parking orbit around binary asteroids is investigated in the current study. To reduce the braking Δ V, a new capture strategy takes advantage of the three-body gravity of the binary asteroid to lower the inertial energy before applying the Δ V. The framework of the circular restricted three-body problem (CR3BP) is employed for the binary asteroid system. The proposed capture strategy is based on the mechanism by which inertial energy can be decreased sharply near zero-velocity curves (ZVCs). The strategy has two steps, namely, hitting the target ZVC and raising the periapsis by a small Δ V at the apoapsis. By hitting the target ZVC, the positive inertial energy decreases and becomes negative. Using a small Δ V, the spacecraft inserts into a bounded orbit around the asteroid. In addition, a rotating mass dipole model is employed for elongated asteroids, which leads to dynamics similar to that of the CR3BP. With this approach, the proposed capture strategy can be applied to elongated asteroids. Numerical simulations validate that the proposed capture strategy is applicable for the binary asteroid 90 Antiope and the elongated asteroid 216 Kleopatra.

Assessment of Dengue virus helicase and methyltransferase as targets for fragment-based drug discovery.

PubMed

Coutard, Bruno; Decroly, Etienne; Li, Changqing; Sharff, Andrew; Lescar, Julien; Bricogne, Gérard; Barral, Karine

2014-06-01

Seasonal and pandemic flaviviruses continue to be leading global health concerns. With the view to help drug discovery against Dengue virus (DENV), a fragment-based experimental approach was applied to identify small molecule ligands targeting two main components of the flavivirus replication complex: the NS3 helicase (Hel) and the NS5 mRNA methyltransferase (MTase) domains. A library of 500 drug-like fragments was first screened by thermal-shift assay (TSA) leading to the identification of 36 and 32 fragment hits binding Hel and MTase from DENV, respectively. In a second stage, we set up a fragment-based X-ray crystallographic screening (FBS-X) in order to provide both validated fragment hits and structural binding information. No fragment hit was confirmed for DENV Hel. In contrast, a total of seven fragments were identified as DENV MTase binders and structures of MTase-fragment hit complexes were solved at resolution at least 2.0Å or better. All fragment hits identified contain either a five- or six-membered aromatic ring or both, and three novel binding sites were located on the MTase. To further characterize the fragment hits identified by TSA and FBS-X, we performed enzymatic assays to assess their inhibition effect on the N7- and 2'-O-MTase enzymatic activities: five of these fragment hits inhibit at least one of the two activities with IC50 ranging from 180μM to 9mM. This work validates the FBS-X strategy for identifying new anti-flaviviral hits targeting MTase, while Hel might not be an amenable target for fragment-based drug discovery (FBDD). This approach proved to be a fast and efficient screening method for FBDD target validation and discovery of starting hits for the development of higher affinity molecules that bind to novel allosteric sites. Copyright © 2014 Elsevier B.V. All rights reserved.

Sepsis Patients with First and Second-Hit Infections Show Different Outcomes Depending on the Causative Organism

PubMed Central

Morgan, Matt P.; Szakmany, Tamas; Power, Sarah G.; Olaniyi, Patrick; Hall, Judith E.; Rowan, Kathy; Eberl, Matthias

2016-01-01

Objective: With improving rates of initial survival in severe sepsis, second-hit infections that occur following resolution of the primary insult carry an increasing burden of morbidity. However, despite the clinical relevance of these infections, no data are available on differential outcomes in patients with first and second-hit infections depending on the nature of the causative organism. This study aims to explore any differences in these subgroups. Design: In a retrospective, observational cohort study, the United Kingdom Intensive Care National Audit & Research Centre (ICNARC) database was used to explore the outcomes of patient with first-hit infections leading to sepsis, and sepsis patients with second-hit infections grouped according to the Gram status of the causative organism. Setting: General critical care units in England, Wales, and Northern Ireland participating in the ICNARC programme between 1 January, 2007 and 30 June, 2012. Patients: Patient groups analyzed included 2119 patients with and 1319 patients without sepsis who developed an intensive care unit acquired infection in blood. Subgroups included patients with trauma, emergency neurosurgery, elective surgery, and cardiogenic shock. Measurements and main results: Gram-negative organisms were associated with poorer outcomes in first-hit infections. The 90-day mortality of patients who developed a Gram-negative infection was 43.6% following elective surgery and 27.9% following trauma. This compared with a mortality of 25.6 and 20.6%, respectively, in Gram-positive infections. Unexpectedly, an inverse relationship between Gram status and mortality was observed in second-hit infections. Patients with an initial diagnosis of sepsis who developed secondary infections caused by Gram-negative organisms had a 90-day mortality of 40.4%, compared with 43.6% in Gram-positive infections. Conclusions: Our study identifies a fundamental difference in patient outcomes between first-hit and second-hit bacterial infections, which may be due to genetic, microbiological, immunological, and environmental factors. This finding has direct implications for risk stratification and defines future research priorities. PMID:26955367

Hitting the Target: Target Setting and Information Systems for the Learning and Skills Sector.

ERIC Educational Resources Information Center

Owen, Jane; Alterman, Jeff

The use of target setting in conjunction with good information systems in colleges and work-based learning (WBL) providers can lead to improved service provisions across the sector in the United Kingdom. Target setting must be carried out in a systematic way in which providers must develop target- setting processes with a focus on learner success;…

Perspectives on Sleep, Sleep Problems, and Their Treatment, in People with Serious Mental Illnesses: A Systematic Review

PubMed Central

Bee, Penny

2016-01-01

Sleep problems are common in people with serious mental illness, and impact negatively on functioning and wellbeing. To understand the development of sleep problems, their maintenance, and their treatment, an in depth understanding of patient perspectives is crucial. A systematic literature review was conducted using Medline, AMED, PsychInfo, Embase and CINAHL. Qualitative and quantitative studies were included if they explored or measured patient perspectives on sleep, sleep problems or sleep treatments in people with serious mental illness. Of the 2,067 hits, only 22 met review inclusion criteria, and high quality evidence was sparse. The limited findings suggested sleep was seen as highly interlinked with mental health. Evaluations of treatments varied, however perceived efficacy and personalisation of treatments were valued. Some evidence suggested patient priorities and conceptualisations regarding sleep may diverge from those of validated screening tools developed in general population and sleep medicine samples. More rigorous research is needed to support adaptation and development of interventions and outcome measures for use in specialist mental health settings. Qualitative studies exploring the experience of sleep disturbance in particular diagnostic groups and contexts are urgently required, as are patient perspectives on sleep interventions. PMID:27657927

Improving the performance of minimizers and winnowing schemes.

PubMed

Marçais, Guillaume; Pellow, David; Bork, Daniel; Orenstein, Yaron; Shamir, Ron; Kingsford, Carl

2017-07-15

The minimizers scheme is a method for selecting k -mers from sequences. It is used in many bioinformatics software tools to bin comparable sequences or to sample a sequence in a deterministic fashion at approximately regular intervals, in order to reduce memory consumption and processing time. Although very useful, the minimizers selection procedure has undesirable behaviors (e.g. too many k -mers are selected when processing certain sequences). Some of these problems were already known to the authors of the minimizers technique, and the natural lexicographic ordering of k -mers used by minimizers was recognized as their origin. Many software tools using minimizers employ ad hoc variations of the lexicographic order to alleviate those issues. We provide an in-depth analysis of the effect of k -mer ordering on the performance of the minimizers technique. By using small universal hitting sets (a recently defined concept), we show how to significantly improve the performance of minimizers and avoid some of its worse behaviors. Based on these results, we encourage bioinformatics software developers to use an ordering based on a universal hitting set or, if not possible, a randomized ordering, rather than the lexicographic order. This analysis also settles negatively a conjecture (by Schleimer et al. ) on the expected density of minimizers in a random sequence. The software used for this analysis is available on GitHub: https://github.com/gmarcais/minimizers.git . gmarcais@cs.cmu.edu or carlk@cs.cmu.edu. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Effects of special composite stretching on the swing of amateur golf players

PubMed Central

Lee, Joong-chul; Lee, Sung-wan; Yeo, Yun-ghi; Park, Gi Duck

2015-01-01

[Purpose] The study investigated stretching for safer a golf swing compared to present stretching methods for proper swings in order to examine the effects of stretching exercises on golf swings. [Subjects] The subjects were 20 amateur golf club members who were divided into two groups: an experimental group which performed stretching, and a control group which did not. The subjects had no bone deformity, muscle weakness, muscle soreness, or neurological problems. [Methods] A swing analyzer and a ROM measuring instrument were used as the measuring tools. The swing analyzer was a GS400-golf hit ball analyzer (Korea) and the ROM measuring instrument was a goniometer (Korea). [Results] The experimental group showed a statistically significant improvement in driving distance. After the special stretching training for golf, a statistically significant difference in hit-ball direction deviation after swings were found between the groups. The experimental group showed statistically significant decreases in hit ball direction deviation. After the special stretching training for golf, statistically significant differences in hit-ball speed were found between the groups. The experimental group showed significant increases in hit-ball speed. [Conclusion] To examine the effects of a special stretching program for golf on golf swing-related factors, 20 male amateur golf club members performed a 12-week stretching training program. After the golf stretching training, statistically significant differences were found between the groups in hit-ball driving distance, direction deviation, deflection distance, and speed. PMID:25995553

Effects of special composite stretching on the swing of amateur golf players.

PubMed

Lee, Joong-Chul; Lee, Sung-Wan; Yeo, Yun-Ghi; Park, Gi Duck

2015-04-01

[Purpose] The study investigated stretching for safer a golf swing compared to present stretching methods for proper swings in order to examine the effects of stretching exercises on golf swings. [Subjects] The subjects were 20 amateur golf club members who were divided into two groups: an experimental group which performed stretching, and a control group which did not. The subjects had no bone deformity, muscle weakness, muscle soreness, or neurological problems. [Methods] A swing analyzer and a ROM measuring instrument were used as the measuring tools. The swing analyzer was a GS400-golf hit ball analyzer (Korea) and the ROM measuring instrument was a goniometer (Korea). [Results] The experimental group showed a statistically significant improvement in driving distance. After the special stretching training for golf, a statistically significant difference in hit-ball direction deviation after swings were found between the groups. The experimental group showed statistically significant decreases in hit ball direction deviation. After the special stretching training for golf, statistically significant differences in hit-ball speed were found between the groups. The experimental group showed significant increases in hit-ball speed. [Conclusion] To examine the effects of a special stretching program for golf on golf swing-related factors, 20 male amateur golf club members performed a 12-week stretching training program. After the golf stretching training, statistically significant differences were found between the groups in hit-ball driving distance, direction deviation, deflection distance, and speed.

Health Information Technology: Meaningful Use and Next Steps to Improving Electronic Facilitation of Medication Adherence.

PubMed

Bosworth, Hayden B; Zullig, Leah L; Mendys, Phil; Ho, Michael; Trygstad, Troy; Granger, Christopher; Oakes, Megan M; Granger, Bradi B

2016-03-15

The use of health information technology (HIT) may improve medication adherence, but challenges for implementation remain. The aim of this paper is to review the current state of HIT as it relates to medication adherence programs, acknowledge the potential barriers in light of current legislation, and provide recommendations to improve ongoing medication adherence strategies through the use of HIT. We describe four potential HIT barriers that may impact interoperability and subsequent medication adherence. Legislation in the United States has incentivized the use of HIT to facilitate and enhance medication adherence. The Health Information Technology for Economic and Clinical Health (HITECH) was recently adopted and establishes federal standards for the so-called "meaningful use" of certified electronic health record (EHR) technology that can directly impact medication adherence. The four persistent HIT barriers to medication adherence include (1) underdevelopment of data reciprocity across clinical, community, and home settings, limiting the capture of data necessary for clinical care; (2) inconsistent data definitions and lack of harmonization of patient-focused data standards, making existing data difficult to use for patient-centered outcomes research; (3) inability to effectively use the national drug code information from the various electronic health record and claims datasets for adherence purposes; and (4) lack of data capture for medication management interventions, such as medication management therapy (MTM) in the EHR. Potential recommendations to address these issues are discussed. To make meaningful, high quality data accessible, and subsequently improve medication adherence, these challenges will need to be addressed to fully reach the potential of HIT in impacting one of our largest public health issues.

Methanol shutdowns cause anxiety

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

Thomas, N.

1996-10-23

European methanol players face an anxious few weeks as unscheduled outages combine with planned turnarounds to make an increasingly tight market. Global markets are also described as tightening, with production problems widely reported in North America. Several European producers were in the middle of shutdown periods when problems at Condea`s 400,000-m.t./year unit at Wesseling, Germany reportedly caused production to run at only 50% of capacity. In addition, the methanol plant at the Leuna refinery is said to be operating at only 60% of capacity, and one producer has had to extend a turnaround period. River levels in Germany are alsomore » low, putting pressure on shipments from Rotterdam. {open_quotes}This is a very difficult situation and we`re living hand to mouth,{close_quotes} says one producer. Producer sources report bids from consumers up to DM280/m.t. T2 fob Rotterdam, but they are unable to obtain extra product. Derivatives makers may also face problems: One methyl tert-butyl ether producer predicts prices {open_quotes}may hit the roof{close_quotes} once feedstock sourcing problems hit home.« less

Making Quality Health Websites a National Public Health Priority: Toward Quality Standards.

PubMed

Devine, Theresa; Broderick, Jordan; Harris, Linda M; Wu, Huijuan; Hilfiker, Sandra Williams

2016-08-02

Most US adults have limited health literacy skills. They struggle to understand complex health information and services and to make informed health decisions. The Internet has quickly become one of the most popular places for people to search for information about their health, thereby making access to quality information on the Web a priority. However, there are no standardized criteria for evaluating Web-based health information. Every 10 years, the US Department of Health and Human Services' Office of Disease Prevention and Health Promotion (ODPHP) develops a set of measurable objectives for improving the health of the nation over the coming decade, known as Healthy People. There are two objectives in Healthy People 2020 related to website quality. The first is objective Health Communication and Health Information Technology (HC/HIT) 8.1: increase the proportion of health-related websites that meet 3 or more evaluation criteria for disclosing information that can be used to assess information reliability. The second is objective HC/HIT-8.2: increase the proportion of health-related websites that follow established usability principles. The ODPHP conducted a nationwide assessment of the quality of Web-based health information using the Healthy People 2020 objectives. The ODPHP aimed to establish (1) a standardized approach to defining and measuring the quality of health websites; (2) benchmarks for measurement; (3) baseline data points to capture the current status of website quality; and (4) targets to drive improvement. The ODPHP developed the National Quality Health Website Survey instrument to assess the quality of health-related websites. The ODPHP used this survey to review 100 top-ranked health-related websites in order to set baseline data points for these two objectives. The ODPHP then set targets to drive improvement by 2020. This study reviewed 100 health-related websites. For objective HC/HIT-8.1, a total of 58 out of 100 (58.0%) websites met 3 or more out of 6 reliability criteria. For objective HC/HIT-8.2, a total of 42 out of 100 (42.0%) websites followed 10 or more out of 19 established usability principles. On the basis of these baseline data points, ODPHP set targets for the year 2020 that meet the minimal statistical significance-increasing objective HC/HIT-8.1 data point to 70.5% and objective HC/HIT-8.2 data point to 55.7%. This research is a critical first step in evaluating the quality of Web-based health information. The criteria proposed by ODPHP provide methods to assess website quality for professionals designing, developing, and managing health-related websites. The criteria, baseline data, and targets are valuable tools for driving quality improvement.

Making Quality Health Websites a National Public Health Priority: Toward Quality Standards

PubMed Central

2016-01-01

Background Most US adults have limited health literacy skills. They struggle to understand complex health information and services and to make informed health decisions. The Internet has quickly become one of the most popular places for people to search for information about their health, thereby making access to quality information on the Web a priority. However, there are no standardized criteria for evaluating Web-based health information. Every 10 years, the US Department of Health and Human Services' Office of Disease Prevention and Health Promotion (ODPHP) develops a set of measurable objectives for improving the health of the nation over the coming decade, known as Healthy People. There are two objectives in Healthy People 2020 related to website quality. The first is objective Health Communication and Health Information Technology (HC/HIT) 8.1: increase the proportion of health-related websites that meet 3 or more evaluation criteria for disclosing information that can be used to assess information reliability. The second is objective HC/HIT-8.2: increase the proportion of health-related websites that follow established usability principles. Objective The ODPHP conducted a nationwide assessment of the quality of Web-based health information using the Healthy People 2020 objectives. The ODPHP aimed to establish (1) a standardized approach to defining and measuring the quality of health websites; (2) benchmarks for measurement; (3) baseline data points to capture the current status of website quality; and (4) targets to drive improvement. Methods The ODPHP developed the National Quality Health Website Survey instrument to assess the quality of health-related websites. The ODPHP used this survey to review 100 top-ranked health-related websites in order to set baseline data points for these two objectives. The ODPHP then set targets to drive improvement by 2020. Results This study reviewed 100 health-related websites. For objective HC/HIT-8.1, a total of 58 out of 100 (58.0%) websites met 3 or more out of 6 reliability criteria. For objective HC/HIT-8.2, a total of 42 out of 100 (42.0%) websites followed 10 or more out of 19 established usability principles. On the basis of these baseline data points, ODPHP set targets for the year 2020 that meet the minimal statistical significance—increasing objective HC/HIT-8.1 data point to 70.5% and objective HC/HIT-8.2 data point to 55.7%. Conclusions This research is a critical first step in evaluating the quality of Web-based health information. The criteria proposed by ODPHP provide methods to assess website quality for professionals designing, developing, and managing health-related websites. The criteria, baseline data, and targets are valuable tools for driving quality improvement. PMID:27485512

High-throughput Identification of DNA-Encoded IgG Ligands that Distinguish Active and Latent Mycobacterium Tuberculosis Infections

PubMed Central

Ndungu, John Maina; Suponitsky-Kroyter, Irena; Cavett, Valerie J.; McEnaney, Patrick J.; MacConnell, Andrew B.; Doran, Todd. M.; Ronacher, Katharina; Stanley, Kim; Utset, Ofelia; Walzl, Gerhard; Paegel, Brian M.; Kodadek, Thomas

2017-01-01

The circulating antibody repertoire encodes a patient's health status and pathogen exposure history, but identifying antibodies with diagnostic potential usually requires knowledge of the antigen(s). We previously circumvented this problem by screening libraries of bead-displayed small molecules against case and control serum samples to discover “epitope surrogates” (ligands of IgGs enriched in the case sample). Here, we describe an improved version of this technology that employs DNA-encoded libraries and high-throughput FACS-based screening to discover epitope surrogates that differentiate noninfectious/latent (LTB) patients from infectious/active TB (ATB) patients, which is imperative for proper treatment selection and antibiotic stewardship. Normal control/LTB (10 patients each, NCL) and ATB (10 patients) serum pools were screened against a library (5 × 106 beads, 448k unique compounds) using fluorescent anti-human IgG to label hit compound beads for FACS. Deep sequencing decoded all hit structures and each hit's occurrence frequencies. ATB hits were pruned of NCL hits and prioritized for resynthesis based on occurrence and homology. Several structurally homologous families were identified and 16/21 resynthesized representative hits validated as selective ligands of ATB serum IgGs (p < 0.005). The native secreted TB protein Ag85B (though not the E. coli recombinant form) competed with one of the validated ligands for binding to antibodies, suggesting that it mimics a native Ag85B epitope. The use of DNA-encoded libraries and FACS-based screening in epitope surrogate discovery reveals thousands of potential hit structures. Distilling this list down to several consensus chemical structures yielded a diagnostic panel for ATB composed of thermally stable and economically produced small molecule ligands in place of protein antigens. PMID:27957856

Validation of extended magnetohydrodynamic simulations of the HIT-SI3 experiment using the NIMROD code

NASA Astrophysics Data System (ADS)

Morgan, K. D.; Jarboe, T. R.; Hossack, A. C.; Chandra, R. N.; Everson, C. J.

2017-12-01

The HIT-SI3 experiment uses a set of inductively driven helicity injectors to apply a non-axisymmetric current drive on the edge of the plasma, driving an axisymmetric spheromak equilibrium in a central confinement volume. These helicity injectors drive a non-axisymmetric perturbation that oscillates in time, with relative temporal phasing of the injectors modifying the mode structure of the applied perturbation. A set of three experimental discharges with different perturbation spectra are modelled using the NIMROD extended magnetohydrodynamics code, and comparisons are made to both magnetic and fluid measurements. These models successfully capture the bulk dynamics of both the perturbation and the equilibrium, though disagreements related to the pressure gradients experimentally measured exist.

Post processing of protein-compound docking for fragment-based drug discovery (FBDD): in-silico structure-based drug screening and ligand-binding pose prediction.

PubMed

Fukunishi, Yoshifumi

2010-01-01

For fragment-based drug development, both hit (active) compound prediction and docking-pose (protein-ligand complex structure) prediction of the hit compound are important, since chemical modification (fragment linking, fragment evolution) subsequent to the hit discovery must be performed based on the protein-ligand complex structure. However, the naïve protein-compound docking calculation shows poor accuracy in terms of docking-pose prediction. Thus, post-processing of the protein-compound docking is necessary. Recently, several methods for the post-processing of protein-compound docking have been proposed. In FBDD, the compounds are smaller than those for conventional drug screening. This makes it difficult to perform the protein-compound docking calculation. A method to avoid this problem has been reported. Protein-ligand binding free energy estimation is useful to reduce the procedures involved in the chemical modification of the hit fragment. Several prediction methods have been proposed for high-accuracy estimation of protein-ligand binding free energy. This paper summarizes the various computational methods proposed for docking-pose prediction and their usefulness in FBDD.

An Ecological Alternative to Snodgrass & Vanderwart: 360 High Quality Colour Images with Norms for Seven Psycholinguistic Variables

PubMed Central

Moreno-Martínez, Francisco Javier; Montoro, Pedro R.

2012-01-01

This work presents a new set of 360 high quality colour images belonging to 23 semantic subcategories. Two hundred and thirty-six Spanish speakers named the items and also provided data from seven relevant psycholinguistic variables: age of acquisition, familiarity, manipulability, name agreement, typicality and visual complexity. Furthermore, we also present lexical frequency data derived from Internet search hits. Apart from the high number of variables evaluated, knowing that it affects the processing of stimuli, this new set presents important advantages over other similar image corpi: (a) this corpus presents a broad number of subcategories and images; for example, this will permit researchers to select stimuli of appropriate difficulty as required, (e.g., to deal with problems derived from ceiling effects); (b) the fact of using coloured stimuli provides a more realistic, ecologically-valid, representation of real life objects. In sum, this set of stimuli provides a useful tool for research on visual object-and word- processing, both in neurological patients and in healthy controls. PMID:22662166

Just in time: technology to disseminate curriculum and manage educational requirements with mobile technology.

PubMed

Ferenchick, Gary; Fetters, Moses; Carse, A Mervyn

2008-01-01

Learning objectives intended to guide clinical education may be of limited usefulness if they are unavailable to students when interacting with patients. We developed, implemented, and evaluated a Web-based process to disseminate the Clerkship Directors of Internal Medicine curricular objectives to students via handheld computers and for students to upload patient logs to a central database. We delivered this program to all students in our geographically dispersed system, with minimal technological problems. The total number of "hits" on curricular objectives was 8,932 (averaging 149 per student or approximately 2.7 times daily). The average number of "hits" per problem was 470, ranging from 18 for smoking cessation to 1,784 for chest pain. The total number of patient problems logged by students was 9,579, and 91% of students met our prespecified criteria for numbers and types of patients. Dissemination and use of curricular learning objectives and related tools is enhanced with mobile technology.

B-HIT - A Tool for Harvesting and Indexing Biodiversity Data

PubMed Central

Barker, Katharine; Braak, Kyle; Cawsey, E. Margaret; Coddington, Jonathan; Robertson, Tim; Whitacre, Jamie

2015-01-01

With the rapidly growing number of data publishers, the process of harvesting and indexing information to offer advanced search and discovery becomes a critical bottleneck in globally distributed primary biodiversity data infrastructures. The Global Biodiversity Information Facility (GBIF) implemented a Harvesting and Indexing Toolkit (HIT), which largely automates data harvesting activities for hundreds of collection and observational data providers. The team of the Botanic Garden and Botanical Museum Berlin-Dahlem has extended this well-established system with a range of additional functions, including improved processing of multiple taxon identifications, the ability to represent associations between specimen and observation units, new data quality control and new reporting capabilities. The open source software B-HIT can be freely installed and used for setting up thematic networks serving the demands of particular user groups. PMID:26544980

B-HIT - A Tool for Harvesting and Indexing Biodiversity Data.

PubMed

Kelbert, Patricia; Droege, Gabriele; Barker, Katharine; Braak, Kyle; Cawsey, E Margaret; Coddington, Jonathan; Robertson, Tim; Whitacre, Jamie; Güntsch, Anton

2015-01-01

With the rapidly growing number of data publishers, the process of harvesting and indexing information to offer advanced search and discovery becomes a critical bottleneck in globally distributed primary biodiversity data infrastructures. The Global Biodiversity Information Facility (GBIF) implemented a Harvesting and Indexing Toolkit (HIT), which largely automates data harvesting activities for hundreds of collection and observational data providers. The team of the Botanic Garden and Botanical Museum Berlin-Dahlem has extended this well-established system with a range of additional functions, including improved processing of multiple taxon identifications, the ability to represent associations between specimen and observation units, new data quality control and new reporting capabilities. The open source software B-HIT can be freely installed and used for setting up thematic networks serving the demands of particular user groups.

When Wife-Beating Is Not Necessarily Abuse: A Feminist and Cross-Cultural Analysis of the Concept of Abuse as Expressed by Tibetan Survivors of Domestic Violence.

PubMed

Rajan, Hamsa

2016-11-20

This article describes the views of Tibetan women who have experienced physical violence from male intimate partners. How they conceptualise abuse, their views on acceptable versus unacceptable hitting, and the acts besides hitting which they felt to be unacceptable or abusive, are explored. Views of survivors' relatives/friends and men who have hit their wives are also included. Western-based domestic violence theory is shown to be incommensurate with abuse in particular socio-cultural settings. As feminist scholars emphasize listening deeply to voices of women in the global South, this article demonstrates how such listening might be undertaken when the views expressed by women diverge from feminism. © The Author(s) 2016.

This is SPIRAL-TAP: Sparse Poisson Intensity Reconstruction ALgorithms--theory and practice.

PubMed

Harmany, Zachary T; Marcia, Roummel F; Willett, Rebecca M

2012-03-01

Observations in many applications consist of counts of discrete events, such as photons hitting a detector, which cannot be effectively modeled using an additive bounded or Gaussian noise model, and instead require a Poisson noise model. As a result, accurate reconstruction of a spatially or temporally distributed phenomenon (f*) from Poisson data (y) cannot be effectively accomplished by minimizing a conventional penalized least-squares objective function. The problem addressed in this paper is the estimation of f* from y in an inverse problem setting, where the number of unknowns may potentially be larger than the number of observations and f* admits sparse approximation. The optimization formulation considered in this paper uses a penalized negative Poisson log-likelihood objective function with nonnegativity constraints (since Poisson intensities are naturally nonnegative). In particular, the proposed approach incorporates key ideas of using separable quadratic approximations to the objective function at each iteration and penalization terms related to l1 norms of coefficient vectors, total variation seminorms, and partition-based multiscale estimation methods.

Powered two-wheeler drivers' risk of hitting a pedestrian in towns.

PubMed

Clabaux, Nicolas; Fournier, Jean-Yves; Michel, Jean-Emmanuel

2014-12-01

The risk of collision between pedestrians and powered two-wheelers is poorly understood today. The objective of this research is to determine the risk for powered two-wheeler drivers of hitting and injuring a pedestrian per kilometer driven in towns and to compare this risk with that run by four-wheeled vehicle drivers. Using the bodily injury accidents recorded by the police on nine roads in the city of Marseille in 2011 and a campaign of observations of powered two-wheeler traffic, we estimated the risk per kilometer driven by powered two-wheeler drivers of hitting a pedestrian and compared it with the risk run by four-wheeled vehicle drivers. The results show that the risk for powered two-wheeler drivers of hitting and injuring a pedestrian is significantly higher than the risk run by four-wheeled vehicle drivers. On the nine roads studied, it is on average 3.33 times higher (95% CI: 1.63; 6.78). Taking four more years into account made it possible to consolidate these results and to tighten the confidence interval. There does indeed seem to be problems in the interactions between pedestrians and powered two-wheeler users in urban traffic. These interaction problems lead to a higher risk of hitting and injuring a pedestrian for powered two-wheeler drivers than for four-wheeled vehicle drivers. The analysis of the police reports suggests that part of this increased risk comes from filtering maneuvers by powered two-wheelers. Possible countermeasures deal with the urban street layout. Measures consisting in reducing the width and the number of traffic lanes to a strict minimum and installing medians or pedestrian islands could be an effective way for the prevention of urban accidents between pedestrians and powered two-wheelers. Copyright © 2014 National Safety Council and Elsevier Ltd. All rights reserved.

Measuring and improving patient safety through health information technology: The Health IT Safety Framework.

PubMed

Singh, Hardeep; Sittig, Dean F

2016-04-01

Health information technology (health IT) has potential to improve patient safety but its implementation and use has led to unintended consequences and new safety concerns. A key challenge to improving safety in health IT-enabled healthcare systems is to develop valid, feasible strategies to measure safety concerns at the intersection of health IT and patient safety. In response to the fundamental conceptual and methodological gaps related to both defining and measuring health IT-related patient safety, we propose a new framework, the Health IT Safety (HITS) measurement framework, to provide a conceptual foundation for health IT-related patient safety measurement, monitoring, and improvement. The HITS framework follows both Continuous Quality Improvement (CQI) and sociotechnical approaches and calls for new measures and measurement activities to address safety concerns in three related domains: 1) concerns that are unique and specific to technology (e.g., to address unsafe health IT related to unavailable or malfunctioning hardware or software); 2) concerns created by the failure to use health IT appropriately or by misuse of health IT (e.g. to reduce nuisance alerts in the electronic health record (EHR)), and 3) the use of health IT to monitor risks, health care processes and outcomes and identify potential safety concerns before they can harm patients (e.g. use EHR-based algorithms to identify patients at risk for medication errors or care delays). The framework proposes to integrate both retrospective and prospective measurement of HIT safety with an organization's existing clinical risk management and safety programs. It aims to facilitate organizational learning, comprehensive 360 degree assessment of HIT safety that includes vendor involvement, refinement of measurement tools and strategies, and shared responsibility to identify problems and implement solutions. A long term framework goal is to enable rigorous measurement that helps achieve the safety benefits of health IT in real-world clinical settings. 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/

Expressing gambling-related cognitive biases in motor behaviour: rolling dice to win prizes.

PubMed

Lim, Matthew S M; Bowden-Jones, Henrietta; Rogers, Robert D

2014-09-01

Cognitive perspectives on gambling propose that biased thinking plays a significant role in sustaining gambling participation and, in vulnerable individuals, gambling problems. One prominent set of cognitive biases include illusions of control involving beliefs that it is possible to influence random gaming events. Sociologists have reported that (some) gamblers believe that it is possible to throw dice in different ways to achieve gaming outcomes (e.g., 'dice-setting' in craps). However, experimental demonstrations of these phenomena are lacking. Here, we asked regular gamblers to roll a computer-simulated, but fair, 6 sided die for monetary prizes. Gamblers allowed the die to roll for longer when attempting to win higher value bets, and when attempting to hit high winning numbers. This behaviour was exaggerated in gamblers motivated to keep gambling following the experience of almost-winning in gambling games. These results suggest that gambling cognitive biases find expression in the motor behaviour of rolling dice for monetary prizes, possibly reflecting embodied substrates.

Pharmacophore Based Virtual Screening Approach to Identify Selective PDE4B Inhibitors

PubMed Central

Gaurav, Anand; Gautam, Vertika

2017-01-01

Phosphodiesterase 4 (PDE4) has been established as a promising target in asthma and chronic obstructive pulmonary disease. PDE4B subtype selective inhibitors are known to reduce the dose limiting adverse effect associated with non-selective PDE4B inhibitors. This makes the development of PDE4B subtype selective inhibitors a desirable research goal. To achieve this goal, ligand based pharmacophore modeling approach is employed. Separate pharmacophore hypotheses for PDE4B and PDE4D inhibitors were generated using HypoGen algorithm and 106 PDE4 inhibitors from literature having thiopyrano [3,2-d] Pyrimidines, 2-arylpyrimidines, and triazines skeleton. Suitable training and test sets were created using the molecules as per the guidelines available for HypoGen program. Training set was used for hypothesis development while test set was used for validation purpose. Fisher validation was also used to test the significance of the developed hypothesis. The validated pharmacophore hypotheses for PDE4B and PDE4D inhibitors were used in sequential virtual screening of zinc database of drug like molecules to identify selective PDE4B inhibitors. The hits were screened for their estimated activity and fit value. The top hit was subjected to docking into the active sites of PDE4B and PDE4D to confirm its selectivity for PDE4B. The hits are proposed to be evaluated further using in-vitro assays. PMID:29201082

Aligning health information technologies with effective service delivery models to improve chronic disease care.

PubMed

Bauer, Amy M; Thielke, Stephen M; Katon, Wayne; Unützer, Jürgen; Areán, Patricia

2014-09-01

Healthcare reforms in the United States, including the Affordable Care and HITECH Acts, and the NCQA criteria for the Patient Centered Medical Home have promoted health information technology (HIT) and the integration of general medical and mental health services. These developments, which aim to improve chronic disease care, have largely occurred in parallel, with little attention to the need for coordination. In this article, the fundamental connections between HIT and improvements in chronic disease management are explored. We use the evidence-based collaborative care model as an example, with attention to health literacy improvement for supporting patient engagement in care. A review of the literature was conducted to identify how HIT and collaborative care, an evidence-based model of chronic disease care, support each other. Five key principles of effective collaborative care are outlined: care is patient-centered, evidence-based, measurement-based, population-based, and accountable. The potential role of HIT in implementing each principle is discussed. Key features of the mobile health paradigm are described, including how they can extend evidence-based treatment beyond traditional clinical settings. HIT, and particularly mobile health, can enhance collaborative care interventions, and thus improve the health of individuals and populations when deployed in integrated delivery systems. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of eight weeks of aerobic interval training and of isoinertial resistance training on risk factors of cardiometabolic diseases and exercise capacity in healthy elderly subjects

PubMed Central

Bruseghini, Paolo; Calabria, Elisa; Tam, Enrico; Milanese, Chiara; Oliboni, Eugenio; Pezzato, Andrea; Pogliaghi, Silvia; Salvagno, Gian Luca; Schena, Federico; Mucelli, Roberto Pozzi; Capelli, Carlo

2015-01-01

We investigated the effect of 8 weeks of high intensity interval training (HIT) and isoinertial resistance training (IRT) on cardiovascular fitness, muscle mass-strength and risk factors of metabolic syndrome in 12 healthy older adults (68 yy ± 4). HIT consisted in 7 two-minute repetitions at 80%–90% of V˙O2max, 3 times/w. After 4 months of recovery, subjects were treated with IRT, which included 4 sets of 7 maximal, bilateral knee extensions/flexions 3 times/w on a leg-press flywheel ergometer. HIT elicited significant: i) modifications of selected anthropometrical features; ii) improvements of cardiovascular fitness and; iii) decrease of systolic pressure. HIT and IRT induced hypertrophy of the quadriceps muscle, which, however, was paralleled by significant increases in strength only after IRT. Neither HIT nor IRT induced relevant changes in blood lipid profile, with the exception of a decrease of LDL and CHO after IRT. Physiological parameters related with aerobic fitness and selected body composition values predicting cardiovascular risk remained stable during detraining and, after IRT, they were complemented by substantial increase of muscle strength, leading to further improvements of quality of life of the subjects. PMID:26046575

Aligning health information technologies with effective service delivery models to improve chronic disease care

PubMed Central

Bauer, Amy M.; Thielke, Stephen M.; Katon, Wayne; Unützer, Jürgen; Areán, Patricia

2014-01-01

Objective Healthcare reforms in the United States, including the Affordable Care and HITECH Acts, and the NCQA criteria for the Patient Centered Medical Home have promoted health information technology (HIT) and the integration of general medical and mental health services. These developments, which aim to improve chronic disease care have largely occurred in parallel, with little attention to the need for coordination. In this article, the fundamental connections between HIT and improvements in chronic disease management are explored. We use the evidence-based collaborative care model as an example, with attention to health literacy improvement for supporting patient engagement in care. Method A review of the literature was conducted to identify how HIT and collaborative care, an evidence-based model of chronic disease care, support each other. Results Five key principles of effective collaborative care are outlined: care is patient-centered, evidence-based, measurement-based, population-based, and accountable. The potential role of HIT in implementing each principle is discussed. Key features of the mobile health paradigm are described, including how they can extend evidence-based treatment beyond traditional clinical settings. Conclusion HIT, and particularly mobile health, can enhance collaborative care interventions, and thus improve the health of individuals and populations when deployed in integrated delivery systems. PMID:24963895

The role of health information technology in care coordination in the United States.

PubMed

Hsiao, Chun-Ju; King, Jennifer; Hing, Esther; Simon, Alan E

2015-02-01

Examine the extent to which office-based physicians in the United States receive patient health information necessary to coordinate care across settings and determine whether receipt of information needed to coordinate care is associated with use of health information technology (HIT) (defined by presence or absence of electronic health record system and electronic sharing of information). Cross-sectional study using the 2012 National Electronic Health Records Survey (65% weighted response rate). Office-based physicians. Use of HIT and 3 types of patient health information needed to coordinate care. In 2012, 64% of physicians routinely received the results of a patient's consultation with a provider outside of their practice, whereas 46% routinely received a patient's history and reason for a referred consultation from a provider outside of their practice. About 54% of physicians reported routinely receiving a patient's hospital discharge information. In adjusted analysis, significant differences in receiving necessary information were observed by use of HIT. Compared with those not using HIT, a lower percentage of physicians who used an electronic health record system and shared patient health information electronically failed to receive the results of outside consultations or patient's history and reason for a referred consultation. No significant differences were observed for the receipt of hospital discharge information by use of HIT. Among physicians routinely receiving information needed for care coordination, at least 54% of them did not receive the information electronically. Although a higher percentage of physicians using HIT received patient information necessary for care coordination than those who did not use HIT, more than one third did not routinely receive the needed patient information at all.

Care coordination gaps due to lack of interoperability in the United States: a qualitative study and literature review.

PubMed

Samal, Lipika; Dykes, Patricia C; Greenberg, Jeffrey O; Hasan, Omar; Venkatesh, Arjun K; Volk, Lynn A; Bates, David W

2016-04-22

Health information technology (HIT) could improve care coordination by providing clinicians remote access to information, improving legibility, and allowing asynchronous communication, among other mechanisms. We sought to determine, from a clinician perspective, how care is coordinated and to what extent HIT is involved when transitioning patients between emergency departments, acute care hospitals, skilled nursing facilities, and home health agencies in settings across the United States. We performed a qualitative study with clinicians and information technology professionals from six regions of the U.S. which were chosen as national leaders in HIT. We analyzed data through a two person consensus approach, assigning responses to each of nine care coordination activities. We also conducted a literature review of MEDLINE®, CINAHL®, and Embase, analyzing results of studies that examined interventions to improve information transfer during transitions of care. We enrolled 29 respondents from 17 organizations and conducted six focus groups. Respondents reported how HIT is currently used for care coordination activities. HIT is currently used to monitor patients and to align systems-level resources with population needs. However, we identified multiple areas where the lack of interoperability leads to inefficient processes and missing data. Additionally, the literature review identified ten intervention studies that address information transfer, seven of which employed HIT and three of which utilized other communication methods such as telephone calls, faxed records, and nurse case management. Significant care coordination gaps exist due to the lack of interoperability across the United States. We must design, evaluate, and incentivize the use of HIT for care coordination. We should focus on the domains where we found the largest gaps: information transfer, systems to monitor patients, tools to support patients' self-management goals, and tools to link patients and their caregivers with community resources.

Toward a comprehensive theory for the sweeping of trapped radiation by inert orbiting matter

NASA Technical Reports Server (NTRS)

Fillius, Walker

1988-01-01

There is a need to calculate loss rates when trapped Van Allen radiation encounters inert orbiting material such as planetary rings and satellites. An analytic expression for the probability of a hit in a bounce encounter is available for all cases where the absorber is spherical and the particles are gyrotropically distributed on a cylindrical flux tube. The hit probability is a function of the particle's pitch angle, the size of the absorber, and the distance between flux tube and absorber, when distances are scaled to the gyroradius of a particle moving perpendicular to the magnetic field. Using this expression, hit probabilities have been computed in drift encounters for all regimes of particle energies and absorber sizes. This technique generalizes the approach to sweeping lifetimes, and is particularly suitable for attacking the inverse problem, where one is given a sweeping signature and wants to deduce the properties of the absorber(s).

Psychology: Climate change hits home

NASA Astrophysics Data System (ADS)

Weber, Elke U.

2011-04-01

Engaging the public with climate change has proved difficult, in part because they see the problem as remote. New evidence suggests that direct experience of one anticipated impact -- flooding -- increases people's concern and willingness to save energy.

The impact of health information technology on organ transplant care: A systematic review.

PubMed

Niazkhani, Zahra; Pirnejad, Habibollah; Rashidi Khazaee, Parviz

2017-04-01

Health Information Technology (HIT) has a potential to promote transplant care. However, a systematic appraisal on how HIT application has so far affected transplant care is greatly missing from the literature. We systematically reviewed trials that evaluated HIT impact on process and patient outcomes as well as costs in organ transplant care. A systematic search was conducted in OVID versions of MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane, and IEEE databases from January 1990 to December 2015. Studies were included if they: (i) evaluated HIT interventions; (ii) reported results for organ transplant population; (iii) reported quantitative data on process, patient, and cost outcomes; and (iv) used a randomized controlled trial or quasi-experimental study design. Primarily, 12,440 publications were identified; from which ten met inclusion criteria. Among HIT systems, uses of clinical decision support systems (CDSS) targeting different aspects of the complex organ transplant care were common. In terms of process outcomes, HIT positively impacted the timeliness of care, laboratory and medication management practices such as promoting therapeutic or diagnostic protocol compliance by clinicians, and reducing medication errors. Regarding patient outcomes, HIT demonstrated a beneficial impact on the percentage of post-transplant patients with normal lab values and decreasing immunosuppressive toxicity and also deviation from the predefined immunosuppressive therapeutic window. However, in terms of mortality, readmission, rejection, and antiviral resistance rates, the impact was not clearly established in the literature. Finally, these systems were associated with savings in the costs of transplant care in three studies. This is the first study reviewing HIT impact on transplant care outcomes. CDSSs have mainly been reported to support transplant care in realizing the above-mentioned benefits. However, to make conclusions, more evidence with less risk of bias is warranted. Several gaps in the literature, including comparison of the impact of commercial systems in different transplant settings, was identified which can motivate future research. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of a pretest scoring system (4Ts) for the diagnosis of heparin-induced thrombocytopenia in a university hospital setting.

PubMed

Vatanparast, Rodina; Lantz, Sarah; Ward, Kristine; Crilley, Pamela Ann; Styler, Michael

2012-11-01

The initial diagnosis of heparin-induced thrombocytopenia (HIT) is made on clinical grounds because the assays with the highest sensitivity (eg, heparin-platelet factor 4 antibody enzyme-linked immunosorbent assay [ELISA]) and specificity (eg, serotonin release assay) may not be readily available. The clinical utility of the pretest scoring system, the 4Ts, was developed and validated by Lo et al in the Journal of Thrombosis and Haemostasis in 2006. The pretest scoring system looks at the degree and timing of thrombocytopenia, thrombosis, and the possibility of other etiologies. Based on the 4T score, patients can be categorized as having a high, intermediate, or low probability of having HIT. We conducted a retrospective study of 100 consecutive patients who were tested for HIT during their hospitalization at Hahnemann University Hospital (Philadelphia, PA) in 2009. Of the 100 patients analyzed, 72, 23, and 5 patients had 4T pretest probability scores of low, intermediate, and high, respectively. A positive HIT ELISA (optical density > 1.0 unit) was detected in 0 of 72 patients (0%) in the low probability group, in 5 of 23 patients (22%) in the intermediate probability group, and in 2 of 5 patients (40%) in the high probability group. The average turnaround time for the HIT ELISA was 4 to 5 days. Fourteen (19%) of the 72 patients with a low pretest probability of HIT were treated with a direct thrombin inhibitor. Ten (71%) of the 14 patients in the low probability group treated with a direct thrombin inhibitor had a major complication of bleeding requiring blood transfusion support. In this retrospective study, a low 4T score showed 100% correlation with a negative HIT antibody assay. We recommend incorporating the 4T scoring system into institutional core measures when assessing a patient with suspected HIT, selecting only patients with intermediate to high probability for therapeutic intervention, which may translate into reduced morbidity and lower health care costs.

Temper Tantrums

MedlinePlus

... set an example for your child. Hitting and spanking don't help. And they send the message ... More Effective Parenting How Can Parents Discipline Without Spanking? Delayed Speech or Language Development Talking to Your ...

An Ethnographically Informed Participatory Design of Primary Healthcare Information Technology in a Developing Country Setting.

PubMed

Shidende, Nima Herman; Igira, Faraja Teddy; Mörtberg, Christina Margaret

2017-01-01

Ethnography, with its emphasis on understanding activities where they occur, and its use of qualitative data gathering techniques rich in description, has a long tradition in Participatory Design (PD). Yet there are limited methodological insights in its application in developing countries. This paper proposes an ethnographically informed PD approach, which can be applied when designing Primary Healthcare Information Technology (PHIT). We use findings from a larger multidisciplinary project, Health Information Systems Project (HISP) to elaborate how ethnography can be used to facilitate participation of health practitioners in developing countries settings as well as indicating the importance of ethnographic approach to participatory Health Information Technology (HIT) designers. Furthermore, the paper discusses the pros and cons of using an ethnographic approach in designing HIT.

Modeling distortion of HIT by an Actuator Disk in a periodic domain

NASA Astrophysics Data System (ADS)

Ghate, Aditya; Ghaisas, Niranjan; Lele, Sanjiva

2017-11-01

We study the distortion of incompressible, homogeneous isotropic turbulence (HIT) by a dragging actuator disk with a fixed thrust coefficient (under the large Reynolds number limit), using Large Eddy Simulation (LES). The HIT inflow is tailored to ensure that the largest length scales in the flow are smaller than the actuator disk diameter in order to minimize the meandering of the turbulent wake and isolate the length scales that undergo distortion. The numerical scheme (Fourier collocation with dealiasing) and the SGS closure (anisotropic minimum dissipation model) are carefully selected to minimize numerical artifacts expected due to the inviscid assumption. The LES is used to characterize the following 3 properties of the flow a) distortion of HIT due to the expanding streamtube resulting in strong anisotropy, b) turbulent pressure modulation across the actuator disk, and the c) turbulent wake state. Finally, we attempt to model the initial distortion and the pressure modulation using a WKB variant of RDT solved numerically using a set of discrete Gabor modes. Funding provided by Precourt Institute for Energy at Stanford University.

Virtual High-Throughput Screening for Matrix Metalloproteinase Inhibitors.

PubMed

Choi, Jun Yong; Fuerst, Rita

2017-01-01

Structure-based virtual screening (SBVS) is a common method for the fast identification of hit structures at the beginning of a medicinal chemistry program in drug discovery. The SBVS, described in this manuscript, is focused on finding small molecule hits that can be further utilized as a starting point for the development of inhibitors of matrix metalloproteinase 13 (MMP-13) via structure-based molecular design. We intended to identify a set of structurally diverse hits, which occupy all subsites (S1'-S3', S2, and S3) centering the zinc containing binding site of MMP-13, by the virtual screening of a chemical library comprising more than ten million commercially available compounds. In total, 23 compounds were found as potential MMP-13 inhibitors using Glide docking followed by the analysis of the structural interaction fingerprints (SIFt) of the docked structures.

Combinatorial therapy discovery using mixed integer linear programming.

PubMed

Pang, Kaifang; Wan, Ying-Wooi; Choi, William T; Donehower, Lawrence A; Sun, Jingchun; Pant, Dhruv; Liu, Zhandong

2014-05-15

Combinatorial therapies play increasingly important roles in combating complex diseases. Owing to the huge cost associated with experimental methods in identifying optimal drug combinations, computational approaches can provide a guide to limit the search space and reduce cost. However, few computational approaches have been developed for this purpose, and thus there is a great need of new algorithms for drug combination prediction. Here we proposed to formulate the optimal combinatorial therapy problem into two complementary mathematical algorithms, Balanced Target Set Cover (BTSC) and Minimum Off-Target Set Cover (MOTSC). Given a disease gene set, BTSC seeks a balanced solution that maximizes the coverage on the disease genes and minimizes the off-target hits at the same time. MOTSC seeks a full coverage on the disease gene set while minimizing the off-target set. Through simulation, both BTSC and MOTSC demonstrated a much faster running time over exhaustive search with the same accuracy. When applied to real disease gene sets, our algorithms not only identified known drug combinations, but also predicted novel drug combinations that are worth further testing. In addition, we developed a web-based tool to allow users to iteratively search for optimal drug combinations given a user-defined gene set. Our tool is freely available for noncommercial use at http://www.drug.liuzlab.org/. zhandong.liu@bcm.edu Supplementary data are available at Bioinformatics online.

Choosing non-redundant representative subsets of protein sequence data sets using submodular optimization.

PubMed

Libbrecht, Maxwell W; Bilmes, Jeffrey A; Noble, William Stafford

2018-04-01

Selecting a non-redundant representative subset of sequences is a common step in many bioinformatics workflows, such as the creation of non-redundant training sets for sequence and structural models or selection of "operational taxonomic units" from metagenomics data. Previous methods for this task, such as CD-HIT, PISCES, and UCLUST, apply a heuristic threshold-based algorithm that has no theoretical guarantees. We propose a new approach based on submodular optimization. Submodular optimization, a discrete analogue to continuous convex optimization, has been used with great success for other representative set selection problems. We demonstrate that the submodular optimization approach results in representative protein sequence subsets with greater structural diversity than sets chosen by existing methods, using as a gold standard the SCOPe library of protein domain structures. In this setting, submodular optimization consistently yields protein sequence subsets that include more SCOPe domain families than sets of the same size selected by competing approaches. We also show how the optimization framework allows us to design a mixture objective function that performs well for both large and small representative sets. The framework we describe is the best possible in polynomial time (under some assumptions), and it is flexible and intuitive because it applies a suite of generic methods to optimize one of a variety of objective functions. © 2018 Wiley Periodicals, Inc.

Rapid immunoassays for diagnosis of heparin-induced thrombocytopenia: Comparison of diagnostic accuracy, reproducibility, and costs in clinical practice

PubMed Central

Bankova, Andriyana; Andres, Yvonne; Horn, Michael P.; Alberio, Lorenzo

2017-01-01

Background Immunoassays are crucial in the work-up of patients with suspected heparin-induced thrombocytopenia (HIT) and rapid tests have been recently developed. However, comparative data on diagnostic accuracy, reproducibility, and analytical costs of different immunoassays in clinical practice are limited. Methods Samples of 179 consecutive patients evaluated for suspected HIT in clinical practice using a polyspecific enzyme-linked immunoabsorbent assay (GTI diagnostics; ELISA) and a rapid particle gel immunoassay (PaGIA), were additionally analysed with a IgG-specific chemiluminescent immunoassay (AcuStar HIT-IgG). Presence of HIT was defined as a positive functional heparin-induced platelet aggregation test. Diagnostic accuracy was determined for low, intermediate and high thresholds as previously established (ELISA: optical density 0.4, 1.3, and 2.0 respectively; PaGIA: positive/negative, titre of 4, titre of 32; AcuStar HIT-IgG: 1.0 U/ml, 2.8, 9.4) and reproducibility was assessed by repeated measurements. Costs of test determination were calculated taking reagents, controls, and working time of technicians according to Swiss health care system into account. Results Data on PaGIA results were available for 171 patients (95.5%), ELISA for 144 patients (80.4%), and AcuStar HIT-IgG for 179 patients (100%). Sensitivity was above 95% for all assays at low and intermediate thresholds. Specificity increased with higher thresholds and was above 90% for all assays with intermediate and high thresholds. Specificity of AcuStar HIT-IgG (92.8%; 95% CI 87.7, 96.2) was significantly higher than PaGIA (83.0%; 95% CI 76.3, 88.5) and higher than ELISA (81.8%, 95% CI 74.2, 88.0) at low threshold (p<0.05). Reproducibility was adequate for all assays. Total costs per test were CHF 51.02 for ELISA, 117.70 for AcuStar HIT-IgG, and 83.13 for PaGIA. Conclusions We observed favourable diagnostic accuracy measures and a high reproducibility for PaGIA and AcuStar HIT-IgG. Implementation into 24-hours-service might improve patient care but the results must be confirmed in other settings and larger populations as well. PMID:28594835

Health information technology to facilitate communication involving health care providers, caregivers, and pediatric patients: a scoping review.

PubMed

Gentles, Stephen James; Lokker, Cynthia; McKibbon, K Ann

2010-06-18

Pediatric patients with health conditions requiring follow-up typically depend on a caregiver to mediate at least part of the necessary two-way communication with health care providers on their behalf. Health information technology (HIT) and its subset, information communication technology (ICT), are increasingly being applied to facilitate communication between health care provider and caregiver in these situations. Awareness of the extent and nature of published research involving HIT interventions used in this way is currently lacking. This scoping review was designed to map the health literature about HIT used to facilitate communication involving health care providers and caregivers (who are usually family members) of pediatric patients with health conditions requiring follow-up. Terms relating to care delivery, information technology, and pediatrics were combined to search MEDLINE, EMBASE, and CINAHL for the years 1996 to 2008. Eligible studies were selected after three rounds of duplicate screening in which all authors participated. Data regarding patient, caregiver, health care provider, HIT intervention, outcomes studied, and study design were extracted and maintained in a Microsoft Access database. Stage of research was categorized using the UK's Medical Research Council (MRC) framework for developing and evaluating complex interventions. Quantitative and qualitative descriptive summaries are presented. We included 104 eligible studies (112 articles) conducted in 17 different countries and representing 30 different health conditions. The most common conditions were asthma, type 1 diabetes, special needs, and psychiatric disorder. Most studies (88, 85%) included children 2 to 12 years of age, and 73 (71%) involved home care settings. Health care providers operated in hospital settings in 96 (92%) of the studies. Interventions featured 12 modes of communication (eg, Internet, intranets, telephone, video conferencing, email, short message service [SMS], and manual downloading of information) used to facilitate 15 categories of functions (eg, support, medication management, education, and monitoring). Numerous patient, caregiver, and health care relevant outcomes have been measured. Most outcomes concerned satisfaction, use, usability, feasibility, and resource use, although behavior changes and quality of life were also reported. Most studies (57 studies, 55%) were pilot phase, with a lesser proportion of development phase (24 studies, 23%) and evaluation phase (11 studies, 11%) studies. HIT interventions addressed several recurring themes in this review: establishing continuity of care, addressing time constraints, and bridging geographical barriers. HIT used in pediatric care involving caregivers has been implemented differently in a range of disease settings, with varying needs influencing the function, form and synchronicity of information transfer. Although some authors have followed a phased approach to development, evaluation and implementation, a greater emphasis on methodological standards such as the MRC guidance for complex interventions would produce more fruitful programs of development and more useful evaluations in the future. This review will be especially helpful to those deciding on areas where further development or research into HIT for this purpose may be warranted.

Reflections on US health care information technology policy from a global perspective.

PubMed

Huerta, Timothy R; Ford, Eric W

2012-01-01

Health information technology (HIT) has been lauded as a foundation upon which the development of an integral solution to cost and quality problems facing many nations is predicated. Countries throughout the world have taken differing approaches in their efforts to advance that foundation through policy, financial, and cultural systems that come to support or hinder adoption. As we explore potential opportunities to learn from the experience of others, we pause to consider the environmental, regulatory, financial, and social dynamics that define the US context. This chapter outlines the framework for a comparative approach through four dimensions--environmental, regulation, financial, and social--through which comparative HIT studies should be explored. With such markedly different contexts in which their HIT is embedded, it is important to not simply look at other countries as a yardstick upon which we compare our failures and successes. Rather, we must look critically at these examples understanding that the dynamics at play in each context have created opportunities and obligations that have come to define each country's implementation. The need for a common framework through which scholars can explore comparative HIT systems, while remaining grounded in the US context is an important aspect of effective knowledge translation in adoption.

Applications of computerized adaptive testing (CAT) to the assessment of headache impact.

PubMed

Ware, John E; Kosinski, Mark; Bjorner, Jakob B; Bayliss, Martha S; Batenhorst, Alice; Dahlöf, Carl G H; Tepper, Stewart; Dowson, Andrew

2003-12-01

To evaluate the feasibility of computerized adaptive testing (CAT) and the reliability and validity of CAT-based estimates of headache impact scores in comparison with 'static' surveys. Responses to the 54-item Headache Impact Test (HIT) were re-analyzed for recent headache sufferers (n = 1016) who completed telephone interviews during the National Survey of Headache Impact (NSHI). Item response theory (IRT) calibrations and the computerized dynamic health assessment (DYNHA) software were used to simulate CAT assessments by selecting the most informative items for each person and estimating impact scores according to pre-set precision standards (CAT-HIT). Results were compared with IRT estimates based on all items (total-HIT), computerized 6-item dynamic estimates (CAT-HIT-6), and a developmental version of a 'static' 6-item form (HIT-6-D). Analyses focused on: respondent burden (survey length and administration time), score distributions ('ceiling' and 'floor' effects), reliability and standard errors, and clinical validity (diagnosis, level of severity). A random sample (n = 245) was re-assessed to test responsiveness. A second study (n = 1103) compared actual CAT surveys and an improved 'static' HIT-6 among current headache sufferers sampled on the Internet. Respondents completed measures from the first study and the generic SF-8 Health Survey; some (n = 540) were re-tested on the Internet after 2 weeks. In the first study, simulated CAT-HIT and total-HIT scores were highly correlated (r = 0.92) without 'ceiling' or 'floor' effects and with a substantial reduction (90.8%) in respondent burden. Six of the 54 items accounted for the great majority of item administrations (3603/5028, 77.6%). CAT-HIT reliability estimates were very high (0.975-0.992) in the range where 95% of respondents scored, and relative validity (RV) coefficients were high for diagnosis (RV = 0.87) and severity (RV = 0.89); patient-level classifications were accurate 91.3% for a diagnosis of migraine. For all three criteria of change, CAT-HIT scores were more responsive than all other measures. In the second study, estimates of respondent burden, item usage, reliability and clinical validity were replicated. The test-retest reliability of CAT-HIT was 0.79 and alternate forms coefficients ranged from 0.85 to 0.91. All correlations with the generic SF-8 were negative. CAT-based administrations of headache impact items achieved very large reductions in respondent burden without compromising validity for purposes of patient screening or monitoring changes in headache impact over time. IRT models and CAT-based dynamic health assessments warrant testing among patients with other conditions.

Pediatric palliative care and eHealth opportunities for patient-centered care.

PubMed

Madhavan, Subha; Sanders, Amy E; Chou, Wen-Ying Sylvia; Shuster, Alex; Boone, Keith W; Dente, Mark A; Shad, Aziza T; Hesse, Bradford W

2011-05-01

Pediatric palliative care currently faces many challenges including unnecessary pain from insufficiently personalized treatment, doctor-patient communication breakdowns, and a paucity of usable patient-centric information. Recent advances in informatics for consumer health through eHealth initiatives have the potential to bridge known communication gaps, but overall these technologies remain under-utilized in practice. This paper seeks to identify effective uses of existing and developing health information technology (HIT) to improve communications and care within the clinical setting. A needs analysis was conducted by surveying seven pediatric oncology patients and their extended support network at the Lombardi Pediatric Clinic at Georgetown University Medical Center in May and June of 2010. Needs were mapped onto an existing inventory of emerging HIT technologies to assess what existing informatics solutions could effectively bridge these gaps. Through the patient interviews, a number of communication challenges and needs in pediatric palliative cancer care were identified from the interconnected group perspective surrounding each patient. These gaps mapped well, in most cases, to existing or emerging cyberinfrastructure. However, adoption and adaptation of appropriate technologies could improve, including for patient-provider communication, behavioral support, pain assessment, and education, all through integration within existing work flows. This study provides a blueprint for more optimal use of HIT technologies, effectively utilizing HIT standards-based technology solutions to improve communication. This research aims to further stimulate the development and adoption of interoperable, standardized technologies and delivery of context-sensitive information to substantially improve the quality of care patients receive within pediatric palliative care clinics and other settings. Copyright © 2011 American Journal of Preventive Medicine. All rights reserved.

Bridging clinical researcher perceptions and health IT realities: A case study of stakeholder creep.

PubMed

Panyard, Daniel J; Ramly, Edmond; Dean, Shannon M; Bartels, Christie M

2018-02-01

We present a case report detailing a challenge in health information technology (HIT) project implementations we term "stakeholder creep": not thoroughly identifying which stakeholders need to be involved and why before starting a project, consequently not understanding the true effort, skill sets, social capital, and time required to complete the project. A root cause analysis was performed post-implementation to understand what led to stakeholder creep. HIT project stakeholders were given a questionnaire to comment on these misconceptions and a proposed implementation tool to help mitigate stakeholder creep. Stakeholder creep contributed to an unexpected increase in time (3-month delayed go-live) and effort (68% over expected HIT work hours). Four main clinician/researcher misconceptions were identified that contributed to the development of stakeholder creep: 1) that EHR IT is a single group; 2) that all EHR IT members know the entire EHR functionality; 3) that changes to an EHR need the input of just a single EHR IT member; and 4) that the technological complexity of a project mirrors the clinical complexity. HIT project stakeholders similarly perceived clinicians/researchers to hold these misconceptions. The proposed stakeholder planning tool was perceived to be feasible and helpful. Stakeholder creep can negatively affect HIT project implementations. Projects may be susceptible to stakeholder creep when clinicians/researchers hold misconceptions related to HIT organization and processes. Implementation tools, such as the proposed stakeholder checklist, could be helpful in preempting and mitigating the effect of stakeholder creep. Copyright © 2017 Elsevier B.V. All rights reserved.

Ship detection in satellite imagery using rank-order greyscale hit-or-miss transforms

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

Harvey, Neal R; Porter, Reid B; Theiler, James

2010-01-01

Ship detection from satellite imagery is something that has great utility in various communities. Knowing where ships are and their types provides useful intelligence information. However, detecting and recognizing ships is a difficult problem. Existing techniques suffer from too many false-alarms. We describe approaches we have taken in trying to build ship detection algorithms that have reduced false alarms. Our approach uses a version of the grayscale morphological Hit-or-Miss transform. While this is well known and used in its standard form, we use a version in which we use a rank-order selection for the dilation and erosion parts of themore » transform, instead of the standard maximum and minimum operators. This provides some slack in the fitting that the algorithm employs and provides a method for tuning the algorithm's performance for particular detection problems. We describe our algorithms, show the effect of the rank-order parameter on the algorithm's performance and illustrate the use of this approach for real ship detection problems with panchromatic satellite imagery.« less

NASA Scatterometer Observes the Extratropical Transition of Pacific Typhoons

NASA Technical Reports Server (NTRS)

Liu, W. Timothy; Tang, Wenquing; Dunbar, R. Scott

1997-01-01

The transition is a facinating science problem, but it also has important economic consequences. The transition occurs over the busiest trans-ocean shipping lane, and when the resulting storms hit land, they usually cause devastation to populated areas.

Effects of Low-Volume, High-Intensity Whole-Body Calisthenics on Army ROTC Cadets.

PubMed

Gist, Nicholas H; Freese, Eric C; Ryan, Terence E; Cureton, Kirk J

2015-05-01

Our objective was to determine the effects of high-intensity interval training (HIT) on fitness in Army Reserve Officers' Training Corps cadets. Twenty-six college-aged (20.5 ± 1.7 years) participants completed 4 weeks of exercise training 3 days · wk(-1) consisting of either approximately 60 minutes of typical physical training or HIT whole-body calisthenics involving 4 to 7 sets of 30-second "all out" burpees separated by 4 minutes of active recovery. Several pre- and postintervention fitness variables were compared. We observed no changes across time or differences between groups in aerobic capacity, anaerobic capacity, or Army Physical Fitness Test performance (p > 0.05). However, there was a significant Group × Time interaction (p = 0.015) for skeletal muscle mitochondrial function (Tc: time constant of recovery). For the typical physical training group, we observed improved mitochondrial function (Tc decreased 2.4 ± 4.6 seconds; Cohen's d = -0.51); whereas, mitochondrial function decreased in HIT (Tc increased 2.4 ± 4.6 seconds; d = 0.50). HIT sustained fitness despite the short duration and reduced volume of activity. A program that includes HIT as part of a larger program may be well suited for maintaining fitness in moderately trained armed forces personnel without access to equipment. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Poisson Statistics of Combinatorial Library Sampling Predict False Discovery Rates of Screening

PubMed Central

2017-01-01

Microfluidic droplet-based screening of DNA-encoded one-bead-one-compound combinatorial libraries is a miniaturized, potentially widely distributable approach to small molecule discovery. In these screens, a microfluidic circuit distributes library beads into droplets of activity assay reagent, photochemically cleaves the compound from the bead, then incubates and sorts the droplets based on assay result for subsequent DNA sequencing-based hit compound structure elucidation. Pilot experimental studies revealed that Poisson statistics describe nearly all aspects of such screens, prompting the development of simulations to understand system behavior. Monte Carlo screening simulation data showed that increasing mean library sampling (ε), mean droplet occupancy, or library hit rate all increase the false discovery rate (FDR). Compounds identified as hits on k > 1 beads (the replicate k class) were much more likely to be authentic hits than singletons (k = 1), in agreement with previous findings. Here, we explain this observation by deriving an equation for authenticity, which reduces to the product of a library sampling bias term (exponential in k) and a sampling saturation term (exponential in ε) setting a threshold that the k-dependent bias must overcome. The equation thus quantitatively describes why each hit structure’s FDR is based on its k class, and further predicts the feasibility of intentionally populating droplets with multiple library beads, assaying the micromixtures for function, and identifying the active members by statistical deconvolution. PMID:28682059

Guided Iterative Substructure Search (GI-SSS) - A New Trick for an Old Dog.

PubMed

Weskamp, Nils

2016-07-01

Substructure search (SSS) is a fundamental technique supported by various chemical information systems. Many users apply it in an iterative manner: they modify their queries to shape the composition of the retrieved hit sets according to their needs. We propose and evaluate two heuristic extensions of SSS aimed at simplifying these iterative query modifications by collecting additional information during query processing and visualizing this information in an intuitive way. This gives the user a convenient feedback on how certain changes to the query would affect the retrieved hit set and reduces the number of trial-and-error cycles needed to generate an optimal search result. The proposed heuristics are simple, yet surprisingly effective and can be easily added to existing SSS implementations. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pharmacophore modeling and virtual screening to identify potential RET kinase inhibitors.

PubMed

Shih, Kuei-Chung; Shiau, Chung-Wai; Chen, Ting-Shou; Ko, Ching-Huai; Lin, Chih-Lung; Lin, Chun-Yuan; Hwang, Chrong-Shiong; Tang, Chuan-Yi; Chen, Wan-Ru; Huang, Jui-Wen

2011-08-01

Chemical features based 3D pharmacophore model for REarranged during Transfection (RET) tyrosine kinase were developed by using a training set of 26 structurally diverse known RET inhibitors. The best pharmacophore hypothesis, which identified inhibitors with an associated correlation coefficient of 0.90 between their experimental and estimated anti-RET values, contained one hydrogen-bond acceptor, one hydrogen-bond donor, one hydrophobic, and one ring aromatic features. The model was further validated by a testing set, Fischer's randomization test, and goodness of hit (GH) test. We applied this pharmacophore model to screen NCI database for potential RET inhibitors. The hits were docked to RET with GOLD and CDOCKER after filtering by Lipinski's rules. Ultimately, 24 molecules were selected as potential RET inhibitors for further investigation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Unintended Consequences: New Problems, New Solutions Contributions From 2015

PubMed Central

Chen, Y.

2016-01-01

Summary Objective To select the best of the 2015 published papers on unintended consequences of healthcare information technology (HIT). Method Literature searches in several areas of scholarship, including IT, human factors, evaluation studies, medical errors, medical informatics, and implementation science. Also, because the specific terms “unintended consequences” were not often included in abstracts and titles, a more nuanced search algorithm was developed. Results We identified 754 papers that had some empirical research on unintended consequences of HIT. An initial screen of titles and abstracts reduced this to 171 papers of potential interest. We then further filtered out papers that did not meet the following criteria: 1) the paper had to report an original empirical investigation, and 2) the impact reported had to be not negligible, i.e., in quantitative studies, the results related to unintended consequences were statistically significant; and in qualitative studies the relevant themes emerged were prominent. This resulted in 33 papers of which 15 were selected as best paper candidates. Each of these 15 papers was then separately evaluated by four reviewers. The final selection of four papers was made jointly by the external reviewers and the two section editors. Conclusions There is a growing awareness of the importance of HIT’s unintended consequences—be they generated by the HIT vendors, the implementation process, the consultants, the users, or most probably, some combination of the above. There has also been greater creativity in use of data sources, including secondary data (e.g., medical malpractice cases and surveys) and a wider acceptance of mixed methods to identify unintended consequences. Unfortunately, the complexity of causes mitigates the value of recommendations to avoid unwanted outcomes. Suggestions are often contentious rather than obvious, setting-specific, and not universally applicable. “Lessons learned” often take on generalized—and perhaps platitudinous—forms, such as: “plan extra time,” “involve all of the stakeholders,” “recognize the different needs of different units or disciplines.” The greater awareness of these problems, and the increased desire to identify and eliminate them is clearly reflected in the area’s growing literature. We are hopeful the topic will receive additional attention and the discipline will improve its ability to identify and address these unexpected and usually adverse outcomes. PMID:27830235

Lessons Learned from Participatory Design in Dementia Care: Placing Care Partners at the Centre.

PubMed

Hendriks, Niels; Slegers, Karin; Wilkinson, Andrea

2017-01-01

In this paper we analyze the participatory design (PD) process of a health information technology (HIT) project. This project, AToM was situated in dementia care and involved partners from academia, industry and care. The analysis specifically focuses on the role of the care partners in the PD process. We will show that the conditions to enable 'good participatory design' were not fully met and we present a set of actions to prevent this in future HIT projects. Central to our recommended approach is placing the care partners at the centre of the PD project.

Mental Health and Self-Esteem of Institutionalized Adolescents Affected by Armed Conflict.

PubMed

War, Firdous Ahmad; Ved, Rifat Saroosh; Paul, Mohammad Altaf

2016-04-01

The primary purpose of this paper was to compare the epidemiology of mental health problems and self-esteem of conflict hit adolescents living in charitable seminaries with their counterparts brought up in natural homes. Substantive body of the literature illustrates the emotional and behavioral issues experienced by these adolescents. In this study, 27 adolescents from a charitable Muslim seminary and 30 adolescents from a regular school were recruited. Self-report measures and clinical interview were used to measure mental health and self-esteem. The findings indicate that adolescents in institution setting may not be having mental health and self-esteem-related issues when compared to adolescents living in intact by parent homes. While the authors acknowledge the limitations of the study, these findings need further research to examine the causes for these differences.

Behind the Curtain: Assessing the Case for National Curriculum Standards. Policy Analysis. No. 661

ERIC Educational Resources Information Center

McCluskey, Neal

2010-01-01

The argument for national curriculum standards sounds simple: set high standards, make all schools meet them, and watch American students achieve at high levels. It is straightforward and compelling, and it is driving a sea change in American education policy. Unfortunately, setting high standards and getting American students to hit them is…

[Patterns of access to information on protection against UV during the Brazilian summer: is there such a thing as the "summer effect"?].

PubMed

Vasconcellos-Silva, Paulo Roberto; Griep, Rosane Harter; de Souza, Miriam Carvalho

2015-08-01

Internet search patterns associated with "windows" of collective interest have been increasingly investigated in the field of public health. This article sets out to identify search patterns relating to the quest for information on skin protection after the perception of excessive exposure to UV radiation - the so-called "summer effect" as it is commonly referred to in Brazil. To calculate the number of hits on the Brazilian National Cancer Institute website - a renowned source of information resources on prevention - log analyzer software was used to measure the volume of hits on specific content pages. The pages on skin protection and self-examination (pages of interest) were monitored over a 48-month period. It was seen that, although the monthly average of hits on pages of interest revealed statistically significant annual growth, the results for the analysis of variance showed no significant differences between the number of hits in the summer compared with other months (p = 0.7491). In short, the perception of intense exposure to the summer sun did not encourage further interest to search for information on prevention.

Present Development and Current Problems about Composite in Our Country

DTIC Science & Technology

1989-12-20

factor of phase structure by SEM observation after hitting it by free vibrating torsion pendulum. The fourth paper is related to composite of Geopolymer ...TW FiLE CO0PY C o FTD-ID (RS) T-0639-89 CD 0 FOREIGN TECHNOLOGY DIVISION I PRESENT DEVELOPMENT AND CURRENT PROBLEMS ABOUT COMPOSITE IN OUR COUNTRY...T-0639-89 20 December 1989 MICROFICHE NR: FTD-90-C-000009 PRESENT DEVELOPMENT AND CURRENT PROBLEMS ABOUT COMPOSITE IN OUR COUNTRY By: Gu Zhenlong

Supporting Primary Care Practices in Building Capacity to Use Health Information Data

PubMed Central

Fernald, Douglas; Wearner, Robyn; Dickinson, W. Perry

2014-01-01

Introduction: Our objective was to describe essential support resources and strategies in order to advance the pace and scope of the use of health information technology (HIT) data. Background and Context: Primary data were collected between January 2011 and October 2012. The primary study population comprised 51 primary care practices enrolled in the Colorado Beacon Consortium in western Colorado. Methods: We used qualitative methods embedded in a mixed-method evaluation: monthly narrative reports from practices; interviews with providers and staff; and focused, group discussions with quality improvement (QI) advisors and staff from the Health Information Technology Regional Extension Center. Findings: Practices valued effective support strategies to assist with using HIT, including the following: translating rules and regulations into individual practice settings; facilitating peer-to-peer connections; providing processes and tools for practice improvement; maintaining accountability and momentum; and providing local electronic health record (EHR) technical expertise. Benefits of support included improved quality measures, operational improvements, increased provider and staff engagement, and deeper understanding of EHR data. Discussion: The findings affirm the utility of practice facilitation for HIT-focused aims with personalized attention and cross-fertilization among practices for improvements. Facilitation to sustain ongoing improvements and prepare for future HIT-intensive improvement activities was highly valued. In addition to the general practice facilitator, an EHR technical expert was critical to improving practice capacity to use electronic clinical data. Collaborative learning expands the pool of mentors and teachers, who can further translate their own lessons into practical advice for their peers, yielding the emergence of a stronger sense of community among the practices. Conclusions: Using HIT more effectively in primary care will require sustained, focused efforts by practices as regulations, incentives and HIT evolve. Ongoing support for community-based practice facilitators; collaborative learning; and local, personalized EHR advisors will help practices care for patients while more effectively deploying HIT to improve care. PMID:25848621

Deferred Maintenance.

ERIC Educational Resources Information Center

DeLong, Richard A.

1984-01-01

Unusually hard hit by the 1970s recession, the University of Michigan accumulated more deferred maintenance problems than could be analyzed efficiently either by hand or with existing computer systems. Using an existing microcomputer and a database management software package, the maintenance service developed its own database to support…

Does exercise intensity affect blood pressure and heart rate in obese adolescents? A 6-month multidisciplinary randomized intervention study.

PubMed

Farah, B Q; Ritti-Dias, R M; Balagopal, P B; Hill, J O; Prado, W L

2014-04-01

Aerobic exercise improves cardiovascular health in general, but whether the impact varies with exercise intensity is not clear. The aim of the current study was to compare the effects of a high-intensity aerobic exercise training (HIT) vs. a low-intensity aerobic exercise training (LIT) on blood pressure (BP), heart rate (HR) and heart rate variability (HRV) in obese adolescents. Forty-three (13-18 years) Tanner stage (III-IV) matched obese adolescents were studied in a randomized trial of either HIT (corresponding to the ventilatory threshold I; n = 20) or LIT (corresponding to 20% below the ventilatory threshold I; n = 23) programme for a period of 6 months. All participants also received a multidisciplinary therapy that included nutritional, psychological and clinical counselling. Both HIT and LIT sessions were isocaloric, with energy expenditure set at 350 kcal. BP, HR and HRV were measured along with markers of body adiposity and insulin resistance before and after the respective interventions. The participants in both groups had similar physical and clinical characteristics. After the 6-month intervention, systolic, diastolic and mean BP decreased (P < 0.05, for all) similarly in both groups, whereas waist circumference, HR and HRV showed beneficial changes only in the HIT group (P < 0.05). Aerobic exercise training set at a high intensity compared with the low intensity appears to have additional benefits on abdominal obesity and cardiovascular health in that it enhances the parasympathetic and autonomic modulation of the heart in obese adolescents. © 2013 The Authors. Pediatric Obesity © 2013 International Association for the Study of Obesity.

Toward Millions of File System IOPS on Low-Cost, Commodity Hardware

PubMed Central

Zheng, Da; Burns, Randal; Szalay, Alexander S.

2013-01-01

We describe a storage system that removes I/O bottlenecks to achieve more than one million IOPS based on a user-space file abstraction for arrays of commodity SSDs. The file abstraction refactors I/O scheduling and placement for extreme parallelism and non-uniform memory and I/O. The system includes a set-associative, parallel page cache in the user space. We redesign page caching to eliminate CPU overhead and lock-contention in non-uniform memory architecture machines. We evaluate our design on a 32 core NUMA machine with four, eight-core processors. Experiments show that our design delivers 1.23 million 512-byte read IOPS. The page cache realizes the scalable IOPS of Linux asynchronous I/O (AIO) and increases user-perceived I/O performance linearly with cache hit rates. The parallel, set-associative cache matches the cache hit rates of the global Linux page cache under real workloads. PMID:24402052

Toward Millions of File System IOPS on Low-Cost, Commodity Hardware.

PubMed

Zheng, Da; Burns, Randal; Szalay, Alexander S

2013-01-01

We describe a storage system that removes I/O bottlenecks to achieve more than one million IOPS based on a user-space file abstraction for arrays of commodity SSDs. The file abstraction refactors I/O scheduling and placement for extreme parallelism and non-uniform memory and I/O. The system includes a set-associative, parallel page cache in the user space. We redesign page caching to eliminate CPU overhead and lock-contention in non-uniform memory architecture machines. We evaluate our design on a 32 core NUMA machine with four, eight-core processors. Experiments show that our design delivers 1.23 million 512-byte read IOPS. The page cache realizes the scalable IOPS of Linux asynchronous I/O (AIO) and increases user-perceived I/O performance linearly with cache hit rates. The parallel, set-associative cache matches the cache hit rates of the global Linux page cache under real workloads.

Lessons from the Canadian national health information technology plan for the United States: opinions of key Canadian experts.

PubMed

Zimlichman, Eyal; Rozenblum, Ronen; Salzberg, Claudia A; Jang, Yeona; Tamblyn, Melissa; Tamblyn, Robyn; Bates, David W

2012-01-01

To summarize the Canadian health information technology (HIT) policy experience and impart lessons learned to the US as it determines its policy in this area. Qualitative analysis of interviews with identified key stakeholders followed by an electronic survey. We conducted semi-structured interviews with 29 key Canadian HIT policy and opinion leaders and used a grounded theory approach to analyze the results. The informant sample was chosen to provide views from different stakeholder groups including national representatives and regional representatives from three Canadian provinces. Canadian informants believed that much of the current US direction is positive, especially regarding incentives and meaningful use, but that there are key opportunities for the US to emphasize direct engagement with providers, define a clear business case for them, sponsor large scale evaluations to assess HIT impact in a broad array of settings, determine standards but also enable access to resources needed for mid-course corrections of standards when issues are identified, and, finally, leverage implementation of digital imaging systems. Not all stakeholder groups were included, such as providers or patients. In addition, as in all qualitative research, a selection bias could be present due to the relatively small sample size. Based on Canadian experience with HIT policy, stakeholders identified as lessons for the US the need to increase direct engagement with providers and the importance of defining the business case for HIT, which can be achieved through large scale evaluations, and of recognizing and leveraging successes as they emerge.

Accuracy and Acceptability of a Screening Tool for Identifying Intimate Partner Violence Perpetration among Women Veterans: A Pre-Implementation Evaluation.

PubMed

Portnoy, Galina A; Haskell, Sally G; King, Matthew W; Maskin, Rachel; Gerber, Megan R; Iverson, Katherine M

2018-06-06

Veterans are at heightened risk for perpetrating intimate partner violence (IPV), yet there is limited evidence to inform practice and policy for the detection of IPV perpetration. The present study evaluated the accuracy and acceptability of a potential IPV perpetration screening tool for use with women veterans. A national sample of women veterans completed a 2016 web-based survey that included a modified 5-item Extended-Hurt/Insult/Threaten/Scream (Modified E-HITS) and the Revised Conflict Tactics Scales (CTS-2). Items also assessed women's perceptions of the acceptability and appropriateness of the modified E-HITS questions for use in healthcare settings. Accuracy statistics, including sensitivity and specificity, were calculated using the CTS-2 as the reference standard. Primary measures included the Modified E-HITS (index test), CTS-2 (reference standard), and items assessing acceptability. This study included 187 women, of whom 31 women veterans (16.6%) reported past-6-month IPV perpetration on the CTS-2. The Modified E-HITS demonstrated good overall accuracy (area under the curve, 0.86; 95% confidence interval, 0.78-0.94). In addition, the majority of women perceived the questions to be acceptable and appropriate. Findings demonstrate that the Modified E-HITS is promising as a low-burden tool for detecting of IPV perpetration among women veterans. This tool may help the Veterans Health Administration and other health care providers detect IPV perpetration and offer appropriate referrals for comprehensive assessment and services. Published by Elsevier Inc.

Relationships between parents' use of corporal punishment and their children's endorsement of spanking and hitting other children.

PubMed

Simons, Dominique A; Wurtele, Sandy K

2010-09-01

To explore the intergenerational cycle of violence, the present study examined the relationship between parental approval and children's approval of corporal punishment (CP) and the subsequent relationship between children's CP experience and preference for hitting to resolve interpersonal conflict. Participants consisted of 102 families, parents, and children, ages 3-7 years old. Parents were assessed on their reported practices and beliefs about corporal punishment using 3 self-report measures. Fifty-four boys and 48 girls were interviewed by researchers to assess their approval of spanking and hitting. Children whose parents approved of and used CP were more likely to endorse hitting as a strategy for resolving interpersonal conflicts with peers and siblings. Frequent spanking was the strongest predictor of children's acceptance of aggressive problem solving, above and beyond parental acceptance, parental experience of CP, and familial demographics. Findings supported an intergenerational cycle of violence; parents who experienced frequent corporal punishment during childhood perceived its use as acceptable and frequently spanked their children. These children, in turn, advocated that spanking be used as a disciplinary method and preferred aggressive conflict resolution strategies with peers and siblings. These findings support an additional "side effect of spanking;" when parents use CP it teaches their children that hitting is an acceptable means of dealing with conflict. Practitioners should encourage parents to avoid using CP as a disciplinary method which could lead to a change in the attitudes and behaviors of the next generation of parents. Copyright © 2010 Elsevier Ltd. All rights reserved.

Intimate partner violence among female drug users admitted to the general hospital: screening and prevalence.

PubMed

Caldentey, Clara; Tirado Muñoz, Judit; Ferrer, Tessie; Fonseca Casals, Francina; Rossi, Paola; Mestre-Pintó, Juan Ignacio; Torrens Melich, Marta

2017-06-28

Intimate partner violence (IPV) is a public health problem worldwide. Several factors have been found to be associated with an increased prevalence of IPV, such as substance use. A cross-sectional study was conducted with the aim of determining the prevalence of IPV among women entering Hospital del Mar (Barcelona) for any medical/surgical reason, and who had a diagnosis of substance use disorder. Secondly, it was intended to psychometrically validate the Spanish version of the Hurt, Insulted, Threatened with Harm, Screamed (HITS) questionnaire. All patients were assessed by two IPV questionnaires, the Composite Abuse Scale (CAS) and HITS. Out of 52 patients interviewed, 46 answered both questionnaires. According to the CAS questionnaire, 23 patients (50%) experienced IPV at some point in their lives and 11 (23.9%) in the last year. Cannabis consumption was also associated with an increased severity of IPV (95% CI 3.5-28.9, p = .013).According to the HITS questionnaire, there was a prevalence of 39.1% (18 patients) in the last 12 months. HITS had a specificity of 100% and a sensitivity of 78% relative to the CAS questionnaire. A cut-off score x∈ [6.7], derived through ROC analysis, correctly discriminated 91% of the victims and 100% of the non-victims. The results obtained showed that the prevalence of IPV was very high among women who suffered from more than one substance use disorder. Therefore, it is highly recommended to systematically screen for IPV victimization by putting the HITS questionnaire into practice.

Stochastic von Bertalanffy models, with applications to fish recruitment.

PubMed

Lv, Qiming; Pitchford, Jonathan W

2007-02-21

We consider three individual-based models describing growth in stochastic environments. Stochastic differential equations (SDEs) with identical von Bertalanffy deterministic parts are formulated, with a stochastic term which decreases, remains constant, or increases with organism size, respectively. Probability density functions for hitting times are evaluated in the context of fish growth and mortality. Solving the hitting time problem analytically or numerically shows that stochasticity can have a large positive impact on fish recruitment probability. It is also demonstrated that the observed mean growth rate of surviving individuals always exceeds the mean population growth rate, which itself exceeds the growth rate of the equivalent deterministic model. The consequences of these results in more general biological situations are discussed.

Release 0.0: clinical information technology in the real world.

PubMed

Kleinke, J D

1998-01-01

The industrialization of medical care delivery, compelled by fifteen years of reimbursement reform, has given rise to a commercial health information technology (HIT) industry. Well financed by Wall Street, the HIT industry offers a variety of ready-made solutions designed to transform a health care organization's raw data resources into useful clinical information. Many of the resulting clinical decision-support products are encumbered by numerous insurmountable intellectual and technical problems and, as a consequence, meet with cultural resistance from physicians. The long-awaited but costly implementation of electronic medical records (EMRs) will make these pioneering but flawed efforts obsolete, if EMR development successfully exploits recent technological breakthroughs and the ongoing consolidation of health care organizations.

Development of an Applied Framework for Understanding Health Information Technology in Nursing Homes.

PubMed

Degenholtz, Howard B; Resnick, Abby; Lin, Michael; Handler, Steven

2016-05-01

There is growing evidence that Health Information Technology (HIT) can play a role in improving quality of care and increasing efficiency in the nursing home setting. Most research in this area, however, has examined whether nursing homes have or use any of a list of available technologies. We sought to develop an empirical framework for understanding the intersection between specific uses of HIT and clinical care processes. Using the nominal group technique, we conducted a series of focus groups with different types of personnel who work in nursing homes (administrators, directors of nursing, physicians, mid-level practitioners, consultant pharmacists, and aides). The resulting framework identified key domain areas that can benefit from HIT: transfer of data, regulatory compliance, quality improvement, structured clinical documentation, medication use process, and communication. The framework can be used to guide both descriptive and normative research. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Fast and Efficient Fragment-Based Lead Generation by Fully Automated Processing and Analysis of Ligand-Observed NMR Binding Data.

PubMed

Peng, Chen; Frommlet, Alexandra; Perez, Manuel; Cobas, Carlos; Blechschmidt, Anke; Dominguez, Santiago; Lingel, Andreas

2016-04-14

NMR binding assays are routinely applied in hit finding and validation during early stages of drug discovery, particularly for fragment-based lead generation. To this end, compound libraries are screened by ligand-observed NMR experiments such as STD, T1ρ, and CPMG to identify molecules interacting with a target. The analysis of a high number of complex spectra is performed largely manually and therefore represents a limiting step in hit generation campaigns. Here we report a novel integrated computational procedure that processes and analyzes ligand-observed proton and fluorine NMR binding data in a fully automated fashion. A performance evaluation comparing automated and manual analysis results on (19)F- and (1)H-detected data sets shows that the program delivers robust, high-confidence hit lists in a fraction of the time needed for manual analysis and greatly facilitates visual inspection of the associated NMR spectra. These features enable considerably higher throughput, the assessment of larger libraries, and shorter turn-around times.

Short read Illumina data for the de novo assembly of a non-model snail species transcriptome (Radix balthica, Basommatophora, Pulmonata), and a comparison of assembler performance

PubMed Central

2011-01-01

Background Until recently, read lengths on the Solexa/Illumina system were too short to reliably assemble transcriptomes without a reference sequence, especially for non-model organisms. However, with read lengths up to 100 nucleotides available in the current version, an assembly without reference genome should be possible. For this study we created an EST data set for the common pond snail Radix balthica by Illumina sequencing of a normalized transcriptome. Performance of three different short read assemblers was compared with respect to: the number of contigs, their length, depth of coverage, their quality in various BLAST searches and the alignment to mitochondrial genes. Results A single sequencing run of a normalized RNA pool resulted in 16,923,850 paired end reads with median read length of 61 bases. The assemblies generated by VELVET, OASES, and SeqMan NGEN differed in the total number of contigs, contig length, the number and quality of gene hits obtained by BLAST searches against various databases, and contig performance in the mt genome comparison. While VELVET produced the highest overall number of contigs, a large fraction of these were of small size (< 200bp), and gave redundant hits in BLAST searches and the mt genome alignment. The best overall contig performance resulted from the NGEN assembly. It produced the second largest number of contigs, which on average were comparable to the OASES contigs but gave the highest number of gene hits in two out of four BLAST searches against different reference databases. A subsequent meta-assembly of the four contig sets resulted in larger contigs, less redundancy and a higher number of BLAST hits. Conclusion Our results document the first de novo transcriptome assembly of a non-model species using Illumina sequencing data. We show that de novo transcriptome assembly using this approach yields results useful for downstream applications, in particular if a meta-assembly of contig sets is used to increase contig quality. These results highlight the ongoing need for improvements in assembly methodology. PMID:21679424

Supervised linear dimensionality reduction with robust margins for object recognition

NASA Astrophysics Data System (ADS)

Dornaika, F.; Assoum, A.

2013-01-01

Linear Dimensionality Reduction (LDR) techniques have been increasingly important in computer vision and pattern recognition since they permit a relatively simple mapping of data onto a lower dimensional subspace, leading to simple and computationally efficient classification strategies. Recently, many linear discriminant methods have been developed in order to reduce the dimensionality of visual data and to enhance the discrimination between different groups or classes. Many existing linear embedding techniques relied on the use of local margins in order to get a good discrimination performance. However, dealing with outliers and within-class diversity has not been addressed by margin-based embedding method. In this paper, we explored the use of different margin-based linear embedding methods. More precisely, we propose to use the concepts of Median miss and Median hit for building robust margin-based criteria. Based on such margins, we seek the projection directions (linear embedding) such that the sum of local margins is maximized. Our proposed approach has been applied to the problem of appearance-based face recognition. Experiments performed on four public face databases show that the proposed approach can give better generalization performance than the classic Average Neighborhood Margin Maximization (ANMM). Moreover, thanks to the use of robust margins, the proposed method down-grades gracefully when label outliers contaminate the training data set. In particular, we show that the concept of Median hit was crucial in order to get robust performance in the presence of outliers.

Nurse adoption of continuous patient monitoring on acute post-surgical units: managing technology implementation.

PubMed

Jeskey, Mary; Card, Elizabeth; Nelson, Donna; Mercaldo, Nathaniel D; Sanders, Neal; Higgins, Michael S; Shi, Yaping; Michaels, Damon; Miller, Anne

2011-10-01

To report an exploratory action-research process used during the implementation of continuous patient monitoring in acute post-surgical nursing units. Substantial US Federal funding has been committed to implementing new health care technology, but failure to manage implementation processes may limit successful adoption and the realisation of proposed benefits. Effective approaches for managing barriers to new technology implementation are needed. Continuous patient monitoring was implemented in three of 13 medical/surgical units. An exploratory action-feedback approach, using time-series nurse surveys, was used to identify barriers and develop and evaluate responses. Post-hoc interviews and document analysis were used to describe the change implementation process. Significant differences were identified in night- and dayshift nurses' perceptions of technology benefits. Research nurses' facilitated the change process by evolving 'clinical nurse implementation specialist' expertise. Health information technology (HIT)-related patient outcomes are mediated through nurses' acting on new information but HIT designed for critical care may not transfer to acute care settings. Exploratory action-feedback approaches can assist nurse managers in assessing and mitigating the real-world effects of HIT implementations. It is strongly recommended that nurse managers identify stakeholders and develop comprehensive plans for monitoring the effects of HIT in their units. © 2011 Blackwell Publishing Ltd.

Mental health problems among survivors in hard-hit areas of the 5.12 Wenchuan and 4.20 Lushan earthquakes.

PubMed

Xie, Zongtang; Xu, Jiuping; Wu, Zhibin

2017-02-01

Earthquake exposure has often been associated with psychological distress. However, little is known about the cumulative effect of exposure to two earthquakes on psychological distress and in particular, the effect on the development of post-traumatic stress disorder (PTSD), anxiety and depression disorders. This study explored the effect of exposure on mental health outcomes after a first earthquake and again after a second earthquake. A population-based mental health survey using self-report questionnaires was conducted on 278 people in the hard-hit areas of Lushan and Baoxing Counties 13-16 months after the Wenchuan earthquake (Sample 1). 191 of these respondents were evaluated again 8-9 months after the Lushan earthquake (Sample 2), which struck almost 5 years after the Wenchuan earthquake. In Sample 1, the prevalence rates for PTSD, anxiety and depression disorders were 44.53, 54.25 and 51.82%, respectively, and in Sample 2 the corresponding rates were 27.27, 38.63 and 36.93%. Females, the middle-aged, those of Tibetan nationality, and people who reported fear during the earthquake were at an increased risk of experiencing post-traumatic symptoms. Although the incidence of PTSD, anxiety and depression disorders decreased from Sample 1 to Sample 2, the cumulative effect of exposure to two earthquakes on mental health problems was serious in the hard-hit areas. Therefore, it is important that psychological counseling be provided for earthquake victims, and especially those exposed to multiple earthquakes.

Heparin-induced thrombocytopenia in the critically ill: interpreting the 4Ts test in a randomized trial.

PubMed

Crowther, Mark; Cook, Deborah; Guyatt, Gordon; Zytaruk, Nicole; McDonald, Ellen; Williamson, David; Albert, Martin; Dodek, Peter; Finfer, Simon; Vallance, Shirley; Heels-Ansdell, Diane; McIntyre, Lauralyn; Mehta, Sangeeta; Lamontagne, Francois; Muscedere, John; Jacka, Michael; Lesur, Olivier; Kutsiogiannis, Jim; Friedrich, Jan; Klinger, James R; Qushmaq, Ismael; Burry, Lisa; Khwaja, Kosar; Sheppard, Jo-Ann; Warkentin, Theodore E

2014-06-01

Thrombocytopenia occurs in 20% to 45% of critically ill medical-surgical patients. The 4Ts heparin-induced thrombocytopenia (HIT) score (with 4 domains: Thrombocytopenia, Timing of thrombocytopenia, Thrombosis and oTher reason[s] for thrombocytopenia) might reliably identify patients at low risk for HIT. Interobserver agreement on 4Ts scoring is uncertain in this setting. To evaluate whether a published clinical prediction rule (the "4Ts score") reliably rules out HIT in "low-risk" intensive care unit (ICU) patients as assessed by research coordinators (who prospectively scored) and 2 adjudicators (who scored retrospectively) during an international heparin thromboprophylaxis trial (PROTECT, NCT00182143). Of 3746 medical-surgical ICU patients in PROTECT, 794 met the enrollment criteria for this HIT substudy. Enrollment was predicated on one of the following occurring in ICU: platelets less than 50×10(9)/L, platelets decreased to 50% of ICU admission value (if admission value<100×10(9)/L), any venous thrombosis, or if HIT was otherwise clinically suspected. Independently, 4Ts scores were completed in real time by research coordinators blinded to study drug and laboratory HIT results, and retrospectively by 2 adjudicators blinded to study drug, laboratory HIT results, and research coordinators' scores; the adjudicators arrived at consensus in all cases. Of the 763 patients, 474 had a central or local laboratory HIT test performed and had 4Ts scoring by adjudicators; 432 were scored by trained research coordinators. Heparin-induced thrombocytopenia was defined by a centrally performed positive serotonin release assay (SRA). Of the 474 patients with central adjudication, 407 (85.9%) had a 4Ts score of 3 or lower, conferring a low pretest probability (PTP) of HIT; of these, 6 (1.5% [95% confidence interval, 0.7%-3.2%) had a positive SRA. Fifty-nine (12.4%) had a moderate PTP (4Ts score of 4-5); of these, 4 (6.8%) had a positive SRA. Eight patients had a high PTP (4Ts score of ≥6); of these, 1 (12.5%) had a positive SRA. Raw agreement between research coordinators and central adjudication on each domain of the 4Ts score and low, intermediate, and high PTP was good. However, chance-corrected agreement was variable between adjudicators (weighted κ values of 0.31-0.93) and between the adjudicator consensus and research coordinators (weighted κ values of 0.13 and 0.78). Post hoc review of the 6 SRA-positive cases with an adjudicated low PTP demonstrated that their scores would have been increased if the adjudicators had had additional information on heparin exposure prior to ICU admission. In general, the fourth domain of 4Ts (oTher causes of thrombocytopenia) generated the most disagreement. Real-time 4Ts scoring by research coordinators at the time of testing for HIT was not consistent with 4Ts scores obtained by central adjudicators. The results of this comprehensive HIT testing highlight the need for further research to improve the assessment of PTP scoring of HIT for critically ill patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Internet-based media coverage on dengue in Sri Lanka between 2007 and 2015.

PubMed

Wilder-Smith, Annelies; Cohn, Emily; Lloyd, David C; Tozan, Yesim; Brownstein, John S

2016-01-01

Internet-based media coverage to explore the extent of awareness of a disease and perceived severity of an outbreak at a national level can be used for early outbreak detection. Dengue has emerged as a major public health problem in Sri Lanka since 2009. To compare Internet references to dengue in Sri Lana with references to other diseases (malaria and influenza) in Sri Lanka and to compare Internet references to dengue in Sri Lanka with notified cases of dengue in Sri Lanka. We examined Internet-based news media articles on dengue queried from HealthMap for Sri Lanka, for the period January 2007 to November 2015. For comparative purposes, we compared hits on dengue with hits on influenza and malaria. There were 565 hits on dengue between 2007 and 2015, with a rapid rise in 2009 and followed by a rising trend ever since. These hits were highly correlated with the national epidemiological trend of dengue. The volume of digital media coverage of dengue was much higher than of influenza and malaria. Dengue in Sri Lanka is receiving increasing media attention. Our findings underpin previous claims that digital media reports reflect national epidemiological trends, both in annual trends and inter-annual seasonal variation, thus acting as proxy biosurveillance to provide early warning and situation awareness of emerging infectious diseases.

A Field Study of Traditional and Nontraditional Children's Baseball.

ERIC Educational Resources Information Center

Martens, Rainer; And Others

1984-01-01

Younger children often have problems playing baseball using adult rules because pitchers lack ability to throw consistently and batters have trouble hitting erratically thrown balls. A modification of adult rules allowed the team coach to pitch to batters. More offensive and defensive activity occurred in the nontraditional games than in…

Development and formative evaluation of the e-Health Implementation Toolkit (e-HIT).

PubMed

Murray, Elizabeth; May, Carl; Mair, Frances

2010-10-18

The use of Information and Communication Technology (ICT) or e-Health is seen as essential for a modern, cost-effective health service. However, there are well documented problems with implementation of e-Health initiatives, despite the existence of a great deal of research into how best to implement e-Health (an example of the gap between research and practice). This paper reports on the development and formative evaluation of an e-Health Implementation Toolkit (e-HIT) which aims to summarise and synthesise new and existing research on implementation of e-Health initiatives, and present it to senior managers in a user-friendly format. The content of the e-HIT was derived by combining data from a systematic review of reviews of barriers and facilitators to implementation of e-Health initiatives with qualitative data derived from interviews of "implementers", that is people who had been charged with implementing an e-Health initiative. These data were summarised, synthesised and combined with the constructs from the Normalisation Process Model. The software for the toolkit was developed by a commercial company (RocketScience). Formative evaluation was undertaken by obtaining user feedback. There are three components to the toolkit--a section on background and instructions for use aimed at novice users; the toolkit itself; and the report generated by completing the toolkit. It is available to download from http://www.ucl.ac.uk/pcph/research/ehealth/documents/e-HIT.xls. The e-HIT shows potential as a tool for enhancing future e-Health implementations. Further work is needed to make it fully web-enabled, and to determine its predictive potential for future implementations.

Development and formative evaluation of the e-Health Implementation Toolkit (e-HIT)

PubMed Central

2010-01-01

Background The use of Information and Communication Technology (ICT) or e-Health is seen as essential for a modern, cost-effective health service. However, there are well documented problems with implementation of e-Health initiatives, despite the existence of a great deal of research into how best to implement e-Health (an example of the gap between research and practice). This paper reports on the development and formative evaluation of an e-Health Implementation Toolkit (e-HIT) which aims to summarise and synthesise new and existing research on implementation of e-Health initiatives, and present it to senior managers in a user-friendly format. Results The content of the e-HIT was derived by combining data from a systematic review of reviews of barriers and facilitators to implementation of e-Health initiatives with qualitative data derived from interviews of "implementers", that is people who had been charged with implementing an e-Health initiative. These data were summarised, synthesised and combined with the constructs from the Normalisation Process Model. The software for the toolkit was developed by a commercial company (RocketScience). Formative evaluation was undertaken by obtaining user feedback. There are three components to the toolkit - a section on background and instructions for use aimed at novice users; the toolkit itself; and the report generated by completing the toolkit. It is available to download from http://www.ucl.ac.uk/pcph/research/ehealth/documents/e-HIT.xls Conclusions The e-HIT shows potential as a tool for enhancing future e-Health implementations. Further work is needed to make it fully web-enabled, and to determine its predictive potential for future implementations. PMID:20955594

"King hit" fatalities in Australia, 2000-2012: the role of alcohol and other drugs.

PubMed

Pilgrim, Jennifer Lucinda; Gerostamoulos, Dimitri; Drummer, Olaf Heino

2014-02-01

"King hits" are when a single blow to the head causes a victim to fall to the ground unconscious, either from the punch itself or the impact between the head and the ground. This can result in fatal skull fractures and subdural hematomas. This study aimed to establish the prevalence of king hit deaths in Australia and determine the involvement of drugs in these violent fatalities. The National Coronial Information System was used to retrieve all cases involving a king hit within Australia between 2000 and 2012. 90 cases were identified with a median age of 33 years (range 15-78). There were 4 females. Most cases occurred in the state of New South Wales (n=28), followed by Victoria and Queensland (24 cases each), at a hotel or pub before 3a.m. Toxicology reports were available in 68 cases. Of these, 53 cases involved the use of alcohol or other drugs (other than those used in hospital treatment). Forty-nine cases (73%) involved the use of alcohol, with a median alcohol concentration of 0.144g/100mL and 0.191g/100mL in ante-mortem and post-mortem specimens, respectively. Illicit drugs were detected in 10 cases of which most involved cannabis. Other pharmaceutical drugs were detected in 3 cases. Assaults are an ongoing problem in Australia and king hits form a large group of these substance-related and often unprovoked attacks. Importantly, this study indicated that alcohol intoxication increases the risk of victimization, not just aggressive offending. This reiterates the serious consequences of alcohol-fueled violence in Australia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Restoration of HST images with missing data

NASA Technical Reports Server (NTRS)

Adorf, Hans-Martin

1992-01-01

Missing data are a fairly common problem when restoring Hubble Space Telescope observations of extended sources. On Wide Field and Planetary Camera images cosmic ray hits and CCD hot spots are the prevalent causes of data losses, whereas on Faint Object Camera images data are lossed due to reseaux marks, blemishes, areas of saturation and the omnipresent frame edges. This contribution discusses a technique for 'filling in' missing data by statistical inference using information from the surrounding pixels. The major gain consists in minimizing adverse spill-over effects to the restoration in areas neighboring those where data are missing. When the mask delineating the support of 'missing data' is made dynamic, cosmic ray hits, etc. can be detected on the fly during restoration.

Mapping the route to medication therapy management documentation and billing standardization and interoperabilility within the health care system: meeting proceedings.

PubMed

Millonig, Marsha K

2009-01-01

To convene a diverse group of stakeholders to discuss medication therapy management (MTM) documentation and billing standardization and its interoperability within the health care system. More than 70 stakeholders from pharmacy, health information systems, insurers/payers, quality, and standard-setting organizations met on October 7-8, 2008, in Bethesda, MD. The American Pharmacists Association (APhA) organized the invitational conference to facilitate discussion on strategic directions for meeting current market need for MTM documentation and billing interoperability and future market needs for MTM integration into electronic health records (EHRs). APhA recently adopted policy that specifically addresses technology barriers and encourages the use and development of standardized systems for the documentation and billing of MTM services. Day 1 of the conference featured six foundational presentations on health information technology (HIT) trends, perspectives on MTM from the profession and the Centers for Medicare & Medicaid Services, health care quality and medication-related outcome measures, integrating MTM workflow in EHRs, and the current state of MTM operalization in practice. After hearing presentations on day 1 and having the opportunity to pose questions to each speaker, conference participants were divided into three breakout groups on day 2. Each group met three times for 60 minutes each and discussed five questions from the perspective of a patient, provider, or payer. Three facilitators met with each of the groups and led discussion from one perspective (i.e., patient, provider, payer). Participants then reconvened as a complete group to participate in a discussion on next steps. HIT is expected to assist in delivering safe, effective, efficient, coordinated care as health professionals strive to improve the quality of care and outcomes for individual patients. The pharmacy profession is actively contributing to quality patient care through MTM services focused on identifying and preventing medication-related problems, improving medication use, and optimizing individual therapeutic outcomes. As MTM programs continue to expand within the health care system, one important limiting factor is the lack of standardization for documentation and billing of MTM services. This lack of interoperability between technology systems, software, and system platforms is presenting as a barrier to MTM service delivery for patients. APhA convened this invitational conference to identify strategic directions to address MTM documentation and billing standardization and interoperability. Participants viewed the meeting as highly successful in bringing together a unique, wide-ranging set of stakeholders, including the government, regulators, standards organizations, other health professions, technology firms, professional organizations, and practitioners, to share perspectives. They strongly encouraged the Association to continue this unique stakeholder dialogue. Participants provided a number of next-step suggestions for APhA to consider because of the event. Participants noted the pharmacy profession's success in building information technology systems for product transactions with systematic, organized, methodical thinking and the need to apply this success to patient services. A unique opportunity exists for the profession to influence and lead the HIT community in creating a workable health technology solution for MTM services. Reaching consensus on minimum data sets for each functional area--clinical, billing, quality improvement--would be a very important short-term gain. Further, participants said it was imperative for pharmacists and the pharmacy community at large to become actively engaged in HIT standards development efforts.

The Fragment Network: A Chemistry Recommendation Engine Built Using a Graph Database.

PubMed

Hall, Richard J; Murray, Christopher W; Verdonk, Marcel L

2017-07-27

The hit validation stage of a fragment-based drug discovery campaign involves probing the SAR around one or more fragment hits. This often requires a search for similar compounds in a corporate collection or from commercial suppliers. The Fragment Network is a graph database that allows a user to efficiently search chemical space around a compound of interest. The result set is chemically intuitive, naturally grouped by substitution pattern and meaningfully sorted according to the number of observations of each transformation in medicinal chemistry databases. This paper describes the algorithms used to construct and search the Fragment Network and provides examples of how it may be used in a drug discovery context.

Korean immigrant discipline and children's social competence and behavior problems.

PubMed

Kim, Eunjung; Guo, Yuqing; Koh, Chinkang; Cain, Kevin C

2010-12-01

The goal of this correlational study was to explore the relationship between Korean immigrant discipline (e.g., positive, appropriate, and harsh discipline) and children's social competence and behavior problems. Self-report data were collected from 58 mothers and 20 fathers of children aged from 3 to 8 years. Only paternal harsh discipline was positively correlated with children's behavior problems. Among specific discipline strategies, maternal physical affection, correcting misbehaviors, and reasoning were positively correlated with children's social competence. Paternal physical punishment (e.g., spanking, hitting, and raising arms) was positively correlated with children's behavior problems. Immigrant fathers need to learn alternative ways of managing children's misbehaviors. Published by Elsevier Inc.

Hit discovery and hit-to-lead approaches.

PubMed

Keseru, György M; Makara, Gergely M

2006-08-01

Hit discovery technologies range from traditional high-throughput screening to affinity selection of large libraries, fragment-based techniques and computer-aided de novo design, many of which have been extensively reviewed. Development of quality leads using hit confirmation and hit-to-lead approaches present their own challenges, depending on the hit discovery method used to identify the initial hits. In this paper, we summarize common industry practices adopted to tackle hit-to-lead challenges and review how the advantages and drawbacks of different hit discovery techniques could affect the various issues hit-to-lead groups face.

Virtual screening of selective multitarget kinase inhibitors by combinatorial support vector machines.

PubMed

Ma, X H; Wang, R; Tan, C Y; Jiang, Y Y; Lu, T; Rao, H B; Li, X Y; Go, M L; Low, B C; Chen, Y Z

2010-10-04

Multitarget agents have been increasingly explored for enhancing efficacy and reducing countertarget activities and toxicities. Efficient virtual screening (VS) tools for searching selective multitarget agents are desired. Combinatorial support vector machines (C-SVM) were tested as VS tools for searching dual-inhibitors of 11 combinations of 9 anticancer kinase targets (EGFR, VEGFR, PDGFR, Src, FGFR, Lck, CDK1, CDK2, GSK3). C-SVM trained on 233-1,316 non-dual-inhibitors correctly identified 26.8%-57.3% (majority >36%) of the 56-230 intra-kinase-group dual-inhibitors (equivalent to the 50-70% yields of two independent individual target VS tools), and 12.2% of the 41 inter-kinase-group dual-inhibitors. C-SVM were fairly selective in misidentifying as dual-inhibitors 3.7%-48.1% (majority <20%) of the 233-1,316 non-dual-inhibitors of the same kinase pairs and 0.98%-4.77% of the 3,971-5,180 inhibitors of other kinases. C-SVM produced low false-hit rates in misidentifying as dual-inhibitors 1,746-4,817 (0.013%-0.036%) of the 13.56 M PubChem compounds, 12-175 (0.007%-0.104%) of the 168 K MDDR compounds, and 0-84 (0.0%-2.9%) of the 19,495-38,483 MDDR compounds similar to the known dual-inhibitors. C-SVM was compared to other VS methods Surflex-Dock, DOCK Blaster, kNN and PNN against the same sets of kinase inhibitors and the full set or subset of the 1.02 M Zinc clean-leads data set. C-SVM produced comparable dual-inhibitor yields, slightly better false-hit rates for kinase inhibitors, and significantly lower false-hit rates for the Zinc clean-leads data set. Combinatorial SVM showed promising potential for searching selective multitarget agents against intra-kinase-group kinases without explicit knowledge of multitarget agents.

The National Council of Churches' Alleged Leftist Bias: To What Degree Did Two Major Media Set the Agenda for Debate on the Issue?

ERIC Educational Resources Information Center

Gentry, Richard H.

In January 1983, the American public read or saw hard-hitting allegations of leftist bias by the National Council of Churches (NCC) in the largest circulation magazine, "Reader's Digest," and on the top-rated television program, "60 Minutes." A study examined the extent to which the media set the agenda for debate on this…

Acute response of high-intensity and traditional resistance exercise on anaerobic power.

PubMed

Austad, Mark A; Gay, Chip R; Murray, Steven R; Pettitt, Robert W

2013-09-01

Quantifying the maximal work capacity (W') above the aerobic critical power (CP) has emerged as a method for estimating anaerobic work capacity. Slower cadence, lower-load resistance training (RT), colloquially referred to as high-intensity training (HIT), is purported to be a better metabolic stressor than faster cadence higher-load RT, but to date, this belief has not been supported by research. We compared the acute effects of HIT and traditional RT bouts on average power within a 150-second time period (P(150 s)), CP, and W', as measured from a 3-minute all-out exercise test using cycling ergometry (3 MT). Eight recreationally active male subjects (mean ± SD: age 22 ± 2 years, body mass 85 ± 14 kg, and height 18 ± 9 cm) completed a baseline 3 MT 10 repetition maximum testing on leg press and leg extension machines, and post-bout 3 MTs after an HIT (4:2 second cadence) or a traditional RT bout (1:1 second cadence). Measurements of CP from the 3 MTs were similar between the baseline, post-HIT (α = 0.96), and post-traditional RT bouts (α = 0.98). Neither HIT (269.2 ± 51.3 W) nor traditional RT (275.1 ± 51.3 W) evoked depreciations (p > 0.05) in P(150 s) from the baseline (275.1 ± 45.4 W). Moreover, estimates of W' at the baseline (8.3 ± 3.2 kJ) were unaffected (p > 0.05) either by the HIT (7.6 ± 2.3 kJ) or by the traditional RT (8.3 ± 1.3 kJ) bouts. These data indicate that the 4:2 cadence is insufficient to exhaust a person's capacity for high-intensity work. Longer RT durations, either by slower cadences or by multiple sets, are necessary to evoke substantive declines on W' and should be investigated.

Generic comparison of protein inference engines.

PubMed

Claassen, Manfred; Reiter, Lukas; Hengartner, Michael O; Buhmann, Joachim M; Aebersold, Ruedi

2012-04-01

Protein identifications, instead of peptide-spectrum matches, constitute the biologically relevant result of shotgun proteomics studies. How to appropriately infer and report protein identifications has triggered a still ongoing debate. This debate has so far suffered from the lack of appropriate performance measures that allow us to objectively assess protein inference approaches. This study describes an intuitive, generic and yet formal performance measure and demonstrates how it enables experimentalists to select an optimal protein inference strategy for a given collection of fragment ion spectra. We applied the performance measure to systematically explore the benefit of excluding possibly unreliable protein identifications, such as single-hit wonders. Therefore, we defined a family of protein inference engines by extending a simple inference engine by thousands of pruning variants, each excluding a different specified set of possibly unreliable identifications. We benchmarked these protein inference engines on several data sets representing different proteomes and mass spectrometry platforms. Optimally performing inference engines retained all high confidence spectral evidence, without posterior exclusion of any type of protein identifications. Despite the diversity of studied data sets consistently supporting this rule, other data sets might behave differently. In order to ensure maximal reliable proteome coverage for data sets arising in other studies we advocate abstaining from rigid protein inference rules, such as exclusion of single-hit wonders, and instead consider several protein inference approaches and assess these with respect to the presented performance measure in the specific application context.

Clinical picture of heparin-induced thrombocytopenia (HIT) and its differentiation from non-HIT thrombocytopenia.

PubMed

Warkentin, Theodore E

2016-10-28

HIT is an acquired antibody-mediated disorder strongly associated with thrombosis, including microthrombosis secondary to disseminated intravascular dissemination (DIC). The clinical features of HIT are reviewed from the perspective of the 4Ts scoring system for HIT, which emphasises its characteristic timing of onset of thrombocytopenia. HIT antibodies recognize multimolecular complexes of platelet factor 4 (PF4)/heparin. However, a subset of HIT sera recognise PF4 bound to platelet chondroitin sulfate; these antibodies activate platelets in vitro and in vivo even in the absence of heparin, thus explaining: delayed-onset HIT (where HIT begins or worsens after stopping heparin); persisting HIT (where HIT takes several weeks to recover); spontaneous HIT syndrome (a disorder clinically and serologically resembling HIT but without proximate heparin exposure); and fondaparinux-associated HIT (four distinct syndromes featuring thrombocytopenia that begins or worsens during treatment with fondaparinux), with a new patient case presented with ongoing thrombocytopenia (and fatal haemorrhage) during treatment of HIT with fondaparinux, with fondaparinux-dependent platelet activation induced by patient serum ("fondaparinux cross-reactivity"). Ironically, despite existence of fondaparinux-associated HIT, this pentasaccharide anticoagulant is a frequent treatment for HIT (including one used by the author). HIT can be confused with other disorders, including those with a) timing similar to HIT (e. g. abciximab-associated thrombocytopenia of delayed-onset); b) combined thrombocytopenia/thrombosis (e. g. symmetrical peripheral gangrene secondary to acute DIC and shock liver); and c) both timing of onset and thrombosis (e. g. warfarin-associated venous limb gangrene complicating cancer-associated DIC). By understanding clinical and pathophysiological similarities and differences between HIT and non-HIT mimicking disorders, the clinician is better able to make the correct diagnosis.

MetaPhinder—Identifying Bacteriophage Sequences in Metagenomic Data Sets

PubMed Central

Villarroel, Julia; Lund, Ole; Voldby Larsen, Mette; Nielsen, Morten

2016-01-01

Bacteriophages are the most abundant biological entity on the planet, but at the same time do not account for much of the genetic material isolated from most environments due to their small genome sizes. They also show great genetic diversity and mosaic genomes making it challenging to analyze and understand them. Here we present MetaPhinder, a method to identify assembled genomic fragments (i.e.contigs) of phage origin in metagenomic data sets. The method is based on a comparison to a database of whole genome bacteriophage sequences, integrating hits to multiple genomes to accomodate for the mosaic genome structure of many bacteriophages. The method is demonstrated to out-perform both BLAST methods based on single hits and methods based on k-mer comparisons. MetaPhinder is available as a web service at the Center for Genomic Epidemiology https://cge.cbs.dtu.dk/services/MetaPhinder/, while the source code can be downloaded from https://bitbucket.org/genomicepidemiology/metaphinder or https://github.com/vanessajurtz/MetaPhinder. PMID:27684958

MetaPhinder-Identifying Bacteriophage Sequences in Metagenomic Data Sets.

PubMed

Jurtz, Vanessa Isabell; Villarroel, Julia; Lund, Ole; Voldby Larsen, Mette; Nielsen, Morten

Bacteriophages are the most abundant biological entity on the planet, but at the same time do not account for much of the genetic material isolated from most environments due to their small genome sizes. They also show great genetic diversity and mosaic genomes making it challenging to analyze and understand them. Here we present MetaPhinder, a method to identify assembled genomic fragments (i.e.contigs) of phage origin in metagenomic data sets. The method is based on a comparison to a database of whole genome bacteriophage sequences, integrating hits to multiple genomes to accomodate for the mosaic genome structure of many bacteriophages. The method is demonstrated to out-perform both BLAST methods based on single hits and methods based on k-mer comparisons. MetaPhinder is available as a web service at the Center for Genomic Epidemiology https://cge.cbs.dtu.dk/services/MetaPhinder/, while the source code can be downloaded from https://bitbucket.org/genomicepidemiology/metaphinder or https://github.com/vanessajurtz/MetaPhinder.

Systematic Refinement of a Health Information Technology Time and Motion Workflow Instrument for Inpatient Nursing Care using a Standardized Interface Terminology

PubMed Central

Zhang, Yi; Monsen, Karen A; Adam, Terrence J; Pieczkiewicz, David S; Daman, Megan; Melton, Genevieve B

2011-01-01

Time and motion (T&M) studies provide an objective method to measure the expenditure of time by clinicians. While some instruments for T&M studies have been designed to evaluate health information technology (HIT), these instruments have not been designed for nursing workflow. We took an existing open source HIT T&M study application designed to evaluate physicians in the ambulatory setting and rationally adapted it through empiric observations to record nursing activities in the inpatient setting and linked this instrument to an existing interface terminology, the Omaha System. Nursing activities involved several dimensions and could include multiple activities occurring simultaneously, requiring significant instrument redesign. 94% of the activities from the study instrument mapped adequately to the Omaha System. T&M study instruments require customization in design optimize them for different environments, such as inpatient nursing, to enable optimal data collection. Interface terminologies show promise as a framework for recording and analyzing T&M study data. PMID:22195228

Incoherent pair generation in a beam-beam interaction simulation

NASA Astrophysics Data System (ADS)

Rimbault, C.; Bambade, P.; Mönig, K.; Schulte, D.

2006-03-01

This paper deals with two topics: the generation of incoherent pairs in two beam-beam simulation programs, GUINEA-PIG and CAIN, and the influence of the International Linear Collider (ILC) beam parameter choices on the background in the micro vertex detector (VD) induced by direct hits. One of the processes involved in incoherent pair creation (IPC) is equivalent to a four fermions interaction and its cross section can be calculated exactly with a dedicated generator, BDK. A comparison of GUINEA-PIG and CAIN results with BDK allows to identify and quantify the uncertainties on IPC background predictions and to benchmark the GUINEA-PIG calculation. Based on this simulation and different VD designs, the five currently suggested ILC beam parameter sets have been compared regarding IPC background induced in the VD by direct IPC hits. We emphasize that the high luminosity set, as it is currently defined, would constrain both the choices of magnetic field and VD inner layer radius.

Development and validation of Indian Affective Picture Database.

PubMed

Sharma, Ujjwal; Bhushan, Braj

2017-11-28

Since culturally salient stimuli for emotion recognition are scarce in India, we developed and validated a set of 140 coloured pictures of six basic emotions along with a neutral expression. The expressions were posed by four expressers, two males and two females, with mean age of 25.25 (SD 3.77) years. The expressions were captured from five different angles keeping the background uniform. These pictures were shown to 350 undergraduates who labelled the emotion and rated their intensity. The mean biased hit rate was 93.02 (SD 7.33) and mean unbiased hit rate was .519 (SD .015). Within subjects ANOVA revealed significant main effect of emotion (F(1, 6) = 7.598, p < .001). The t-test value (23.116, p < .001) shows that the given emotion was identified correctly by participants beyond chance factors. The mean intensity rating was 5.94 (SD .77). Overall, the results reveal that the pictures are a valid set of affective stimuli. © 2017 International Union of Psychological Science.

Free boundary problems in shock reflection/diffraction and related transonic flow problems

PubMed Central

Chen, Gui-Qiang; Feldman, Mikhail

2015-01-01

Shock waves are steep wavefronts that are fundamental in nature, especially in high-speed fluid flows. When a shock hits an obstacle, or a flying body meets a shock, shock reflection/diffraction phenomena occur. In this paper, we show how several long-standing shock reflection/diffraction problems can be formulated as free boundary problems, discuss some recent progress in developing mathematical ideas, approaches and techniques for solving these problems, and present some further open problems in this direction. In particular, these shock problems include von Neumann's problem for shock reflection–diffraction by two-dimensional wedges with concave corner, Lighthill's problem for shock diffraction by two-dimensional wedges with convex corner, and Prandtl-Meyer's problem for supersonic flow impinging onto solid wedges, which are also fundamental in the mathematical theory of multidimensional conservation laws. PMID:26261363

Salmonella Smorgasbord: The Problem with too Many Choices

USDA-ARS?s Scientific Manuscript database

Although hundreds of articles are written about Salmonella each year, it continues to command top billing as a food borne pathogen. We have revisited the same issues over a period of time without hitting upon a ‘eureka’ moment. Often, we tend to travel in the comfort zone, bringing in the latest ...

Training Policy Students to Hit the Ground Running: The Design of an Integrative Core Course

ERIC Educational Resources Information Center

Chetkovich, Carol; Henderson, Mark

2014-01-01

Effective public policy education must prepare students both to integrate the lessons of multiple disciplines and to apply these across diverse substantive areas. How can these objectives best be accomplished? Research on adult learning and professional education points toward applied, problem-based, cooperative, and student-driven pedagogy. This…

Citizen Science: A Gateway for Innovation in Disease-Carrying Mosquito Management?

PubMed

Bartumeus, Frederic; Oltra, Aitana; Palmer, John R B

2018-05-21

Traditional methods for tracking disease-carrying mosquitoes are hitting budget constraints as the scales over which they must be implemented grow exponentially. Citizen science offers a novel solution to this problem but requires new models of innovation in the public health sector. Copyright © 2018 Elsevier Ltd. All rights reserved.

Part of the Solution, No Matter the Problem

ERIC Educational Resources Information Center

Reeves, Melissa A.; Cowan, Katherine C.; Skalski, Anastasia Kalamaros

2009-01-01

The economic downturn is hitting schools hard, and in many places, school psychologists are seeing positions cut, services limited, and roles redefined. At the same time, the need for prevention and intervention services is skyrocketing as children, families, and staff suffer the effects of lost incomes, homes, and stability. Forces that may seem…

Bullying in Schools. ERIC Digest.

ERIC Educational Resources Information Center

Banks, Ron

Bullying is a serious problem that can dramatically affect the ability of students to progress academically and socially. Bullying is comprised of direct behaviors such as teasing, taunting, threatening, hitting, and stealing that are initiated by one or more students against a victim. Bullying may also be more indirect by causing a student to be…

What Will Colleges Do when the Bubble Bursts?

ERIC Educational Resources Information Center

Shaw, Jane S.

2011-01-01

The problem facing American colleges and universities is larger than even the term "bubble" implies. A bursting bubble would force change on the more than four thousand postsecondary institutions in the United States, but something even more destructive is going to hit higher education, probably at the same time. The major sign that a…

Constitution or Conformity: When the Shirt Hits the Fan in Public Schools.

ERIC Educational Resources Information Center

Weisenberger, Clay

2000-01-01

Examines message T-Shirts as a medium for student expression and the ability of public schools to regulate those messages. Predicts that as violence and insolence increase in schools, courts will probably continue to defer to school authorities and let them handle their own problems. (77 footnotes). (MLF)

Acceptance of clinical decision support surveillance technology in the clinical pharmacy.

PubMed

English, Dan; Ankem, Kalyani; English, Kathleen

2017-03-01

There are clinical and economic benefits to incorporating clinical decision support systems (CDSSs) in patient care interventions in the clinical pharmacy setting. However, user dissatisfaction and resistance to HIT can prevent optimal use of such systems, particularly when users employ system workarounds and overrides. The present study applied a modified version of the unified theory of acceptance and use of technology (UTAUT) to evaluate the disposition and satisfaction with CDSS among clinical pharmacists who perform surveillance to identify potential medication therapy interventions on patients in the hospital setting. A survey of clinical pharmacists (N = 48) was conducted. Partial least squares (PLS) regression was used to analyze the influence of the UTAUT-related variables on behavioral intention and satisfaction with CDSS among clinical pharmacists. While behavioral intention did not predict actual use of HIT, facilitating conditions had a direct effect on pharmacists' use of CDSS. Likewise, satisfaction with CDSS was found to have a direct effect on use, with more satisfied users being less inclined to employ workarounds or overrides of the system. Based on the findings, organizational structures that facilitate CDSS use and user satisfaction affect the extent to which pharmacy and health care management maximize use in the clinical pharmacy setting.

What's that gene (or protein)? Online resources for exploring functions of genes, transcripts, and proteins

PubMed Central

Hutchins, James R. A.

2014-01-01

The genomic era has enabled research projects that use approaches including genome-scale screens, microarray analysis, next-generation sequencing, and mass spectrometry–based proteomics to discover genes and proteins involved in biological processes. Such methods generate data sets of gene, transcript, or protein hits that researchers wish to explore to understand their properties and functions and thus their possible roles in biological systems of interest. Recent years have seen a profusion of Internet-based resources to aid this process. This review takes the viewpoint of the curious biologist wishing to explore the properties of protein-coding genes and their products, identified using genome-based technologies. Ten key questions are asked about each hit, addressing functions, phenotypes, expression, evolutionary conservation, disease association, protein structure, interactors, posttranslational modifications, and inhibitors. Answers are provided by presenting the latest publicly available resources, together with methods for hit-specific and data set–wide information retrieval, suited to any genome-based analytical technique and experimental species. The utility of these resources is demonstrated for 20 factors regulating cell proliferation. Results obtained using some of these are discussed in more depth using the p53 tumor suppressor as an example. This flexible and universally applicable approach for characterizing experimental hits helps researchers to maximize the potential of their projects for biological discovery. PMID:24723265

Screening of HIV-1 Protease Using a Combination of an Ultra-High-Throughput Fluorescent-Based Assay and RapidFire Mass Spectrometry.

PubMed

Meng, Juncai; Lai, Ming-Tain; Munshi, Vandna; Grobler, Jay; McCauley, John; Zuck, Paul; Johnson, Eric N; Uebele, Victor N; Hermes, Jeffrey D; Adam, Gregory C

2015-06-01

HIV-1 protease (PR) represents one of the primary targets for developing antiviral agents for the treatment of HIV-infected patients. To identify novel PR inhibitors, a label-free, high-throughput mass spectrometry (HTMS) assay was developed using the RapidFire platform and applied as an orthogonal assay to confirm hits identified in a fluorescence resonance energy transfer (FRET)-based primary screen of > 1 million compounds. For substrate selection, a panel of peptide substrates derived from natural processing sites for PR was evaluated on the RapidFire platform. As a result, KVSLNFPIL, a new substrate measured to have a ~ 20- and 60-fold improvement in k cat/K m over the frequently used sequences SQNYPIVQ and SQNYPIV, respectively, was identified for the HTMS screen. About 17% of hits from the FRET-based primary screen were confirmed in the HTMS confirmatory assay including all 304 known PR inhibitors in the set, demonstrating that the HTMS assay is effective at triaging false-positives while capturing true hits. Hence, with a sampling rate of ~7 s per well, the RapidFire HTMS assay enables the high-throughput evaluation of peptide substrates and functions as an efficient tool for hits triage in the discovery of novel PR inhibitors. © 2015 Society for Laboratory Automation and Screening.

A Path Algorithm for Constrained Estimation

PubMed Central

Zhou, Hua; Lange, Kenneth

2013-01-01

Many least-square problems involve affine equality and inequality constraints. Although there are a variety of methods for solving such problems, most statisticians find constrained estimation challenging. The current article proposes a new path-following algorithm for quadratic programming that replaces hard constraints by what are called exact penalties. Similar penalties arise in l1 regularization in model selection. In the regularization setting, penalties encapsulate prior knowledge, and penalized parameter estimates represent a trade-off between the observed data and the prior knowledge. Classical penalty methods of optimization, such as the quadratic penalty method, solve a sequence of unconstrained problems that put greater and greater stress on meeting the constraints. In the limit as the penalty constant tends to ∞, one recovers the constrained solution. In the exact penalty method, squared penalties!are replaced by absolute value penalties, and the solution is recovered for a finite value of the penalty constant. The exact path-following method starts at the unconstrained solution and follows the solution path as the penalty constant increases. In the process, the solution path hits, slides along, and exits from the various constraints. Path following in Lasso penalized regression, in contrast, starts with a large value of the penalty constant and works its way downward. In both settings, inspection of the entire solution path is revealing. Just as with the Lasso and generalized Lasso, it is possible to plot the effective degrees of freedom along the solution path. For a strictly convex quadratic program, the exact penalty algorithm can be framed entirely in terms of the sweep operator of regression analysis. A few well-chosen examples illustrate the mechanics and potential of path following. This article has supplementary materials available online. PMID:24039382

e-Health readiness assessment factors and measuring tools: A systematic review.

PubMed

Yusif, Salifu; Hafeez-Baig, Abdul; Soar, Jeffrey

2017-11-01

The evolving, adoption and high failure nature of health information technology (HIT)/IS/T systems requires effective readiness assessment to avert increasing failures while increasing system benefits. However, literature on HIT readiness assessment is myriad and fragmented. This review bares the contours of the available literature concluding in a set of manageable and usable recommendations for policymakers, researchers, individuals and organizations intending to assess readiness for any HIT implementation. Identify studies, analyze readiness factors and offer recommendations. Published articles 1995-2016 were searched using Medline/PubMed, Cinahl, Web of Science, PsychInfo, ProQuest. Studies were included if they were assessing IS/T/mHealth readiness in the context of HIT. Articles not written in English were excluded. Themes that emerged in the process of the data synthesis were thematically analysed and interpreted. Analyzed themes were found across 63 articles. In accordance with their prevalence of use, they included but not limited to "Technological readiness", 30 (46%); "Core/Need/Motivational readiness", 23 (37%); "Acceptance and use readiness", 19 (29%); "Organizational readiness", 20 (21%); "IT skills/Training/Learning readiness" (18%), "Engagement readiness", 16 (24%) and "Societal readiness" (14%). Despite their prevalence in use, "Technological readiness", "Motivational readiness" and "Engagement readiness" all had myriad and unreliable measuring tools. Core readiness had relatively reliable measuring tools, which repeatedly been used in various readiness assessment studies CONCLUSION: Thus, there is the need for reliable measuring tools for even the most commonly used readiness assessment factors/constructs: Core readiness, Engagement and buy-ins readiness, Technological readiness and IT Skills readiness as this could serve as an immediate step in conducting effective/reliable e-Health readiness assessment, which could lead to reduced HIT implementation failures. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of potential glutaminyl cyclase inhibitors from lead-like libraries by in silico and in vitro fragment-based screening.

PubMed

Szaszkó, Mária; Hajdú, István; Flachner, Beáta; Dobi, Krisztina; Magyar, Csaba; Simon, István; Lőrincz, Zsolt; Kapui, Zoltán; Pázmány, Tamás; Cseh, Sándor; Dormán, György

2017-02-01

A glutaminyl cyclase (QC) fragment library was in silico selected by disconnection of the structure of known QC inhibitors and by lead-like 2D virtual screening of the same set. The resulting fragment library (204 compounds) was acquired from commercial suppliers and pre-screened by differential scanning fluorimetry followed by functional in vitro assays. In this way, 10 fragment hits were identified ([Formula: see text]5 % hit rate, best inhibitory activity: 16 [Formula: see text]). The in vitro hits were then docked to the active site of QC, and the best scoring compounds were analyzed for binding interactions. Two fragments bound to different regions in a complementary manner, and thus, linking those fragments offered a rational strategy to generate novel QC inhibitors. Based on the structure of the virtual linked fragment, a 77-membered QC target focused library was selected from vendor databases and docked to the active site of QC. A PubChem search confirmed that the best scoring analogues are novel, potential QC inhibitors.

Learning PDA skills online is feasible and acceptable to clerkship students.

PubMed

Strayer, Scott M; Williams, Pamela M; Stephens, Mark B; Yew, Kenneth S

2008-01-01

The feasibility and acceptability of teaching medical students to use PDA clinical decision support tools via a Web-based course have not been previously evaluated. A total of 119 third-year family medicine clerkship students completed a baseline survey on PDA use, attended an introductory PDA lecture, and were invited to voluntarily access a Web-based course through Blackboard. All students had been previously issued with PDAs in their second year. At baseline, 95% of students reported having removed their PDA from its box, 59% reported using it weekly, and 71% had loaded medical applications. From August 2006--March 2007, 36 students accessed the course 610 times (range 8-54). The PDA cases comprised 63% of hits, course resources 30% of hits, and course information 6% of hits. Students evaluated the course equally to other clerkship didactics. It is feasible and acceptable to students to teach PDA decision support tools in an online course. In our setting, for the minority of students who chose to learn online, the format was successful and met their needs.

Pediatric aspects of inpatient health information technology systems.

PubMed

Lehmann, Christoph U

2015-03-01

In the past 3 years, the Health Information Technology for Economic and Clinical Health Act accelerated the adoption of electronic health records (EHRs) with providers and hospitals, who can claim incentive monies related to meaningful use. Despite the increase in adoption of commercial EHRs in pediatric settings, there has been little support for EHR tools and functionalities that promote pediatric quality improvement and patient safety, and children remain at higher risk than adults for medical errors in inpatient environments. Health information technology (HIT) tailored to the needs of pediatric health care providers can improve care by reducing the likelihood of errors through information assurance and minimizing the harm that results from errors. This technical report outlines pediatric-specific concepts, child health needs and their data elements, and required functionalities in inpatient clinical information systems that may be missing in adult-oriented HIT systems with negative consequences for pediatric inpatient care. It is imperative that inpatient (and outpatient) HIT systems be adapted to improve their ability to properly support safe health care delivery for children. Copyright © 2015 by the American Academy of Pediatrics.

Screening of agelasine D and analogs for inhibitory activity against pathogenic protozoa; identification of hits for visceral leishmaniasis and Chagas disease.

PubMed

Vik, Anders; Proszenyák, Agnes; Vermeersch, Marieke; Cos, Paul; Maes, Louis; Gundersen, Lise-Lotte

2009-01-08

There is an urgent need for novel and improved drugs against several tropical diseases caused by protozoa. The marine sponge (Agelas sp.) metabolite agelasine D, as well as other agelasine analogs and related structures were screened for inhibitory activity against Plasmodium falciparum, Leishmania infantum, Trypanosoma brucei and T. cruzi, as well as for toxicity against MRC-5 fibroblast cells. Many compounds displayed high general toxicity towards both the protozoa and MRC-5 cells. However, two compounds exhibited more selective inhibitory activity against L. infantum (IC(50) <0.5 microg/mL) while two others displayed IC(50) <1 microg/mL against T. cruzi in combination with relatively low toxicity against MRC-5 cells. According to criteria set up by the WHO Special Programme for Research & Training in Tropical Diseases (TDR), these compounds could be classified as hits for leishmaniasis and for Chagas disease, respectively. Identification of the hits as well as other SAR data from this initial screening will be valuable for design of more potent and selective potential drugs against these neglected tropical diseases.

A Prospective Virtual Screening Study: Enriching Hit Rates and Designing Focus Libraries To Find Inhibitors of PI3Kδ and PI3Kγ.

PubMed

Damm-Ganamet, Kelly L; Bembenek, Scott D; Venable, Jennifer W; Castro, Glenda G; Mangelschots, Lieve; Peeters, Daniëlle C G; Mcallister, Heather M; Edwards, James P; Disepio, Daniel; Mirzadegan, Taraneh

2016-05-12

Here, we report a high-throughput virtual screening (HTVS) study using phosphoinositide 3-kinase (both PI3Kγ and PI3Kδ). Our initial HTVS results of the Janssen corporate database identified small focused libraries with hit rates at 50% inhibition showing a 50-fold increase over those from a HTS (high-throughput screen). Further, applying constraints based on "chemically intuitive" hydrogen bonds and/or positional requirements resulted in a substantial improvement in the hit rates (versus no constraints) and reduced docking time. While we find that docking scoring functions are not capable of providing a reliable relative ranking of a set of compounds, a prioritization of groups of compounds (e.g., low, medium, and high) does emerge, which allows for the chemistry efforts to be quickly focused on the most viable candidates. Thus, this illustrates that it is not always necessary to have a high correlation between a computational score and the experimental data to impact the drug discovery process.

Interface Usability Across and Within EHR Vendors and Medical Settings: The Often Unexamined Need for Interface Similarities.

PubMed

Koppel, Ross; Kuziemsky, Craig

2017-01-01

Usability of health information technology (HIT), if considered at all, is usually focused on individual providers, settings and vendors. However, in light of transformative models of healthcare delivery such as collaborative care delivery that crosses providers and settings, we need to think of usability as a collective and constantly emerging process. To address this new reality we develop a matrix of usability that spans several dimensions and contexts, incorporating differing vendors, user, settings, disciplines, and display configurations. The matrix, while conceptual, extends existing work by providing the means for discussion of usability issues and needs beyond one setting and one user type.

Heidelberg Interaction Training for Language Promotion in Early Childhood Settings (HIT)

ERIC Educational Resources Information Center

Buschmann, Anke; Sachse, Steffi

2018-01-01

Beside parents, teachers in early childhood education and care have the greatest potential to foster language acquisition in children. This is especially important for children with language delays, language disorders or bi-/multilingual children. However, they present teachers with a particular challenge in language support. Therefore, integrated…

Sandia National Laboratories: CRISPR genome-editing technology

Science.gov Websites

boom sets records, forges ties "Like a jar of jellybeans, a pooled CRISPR library is a complex like individually wrapped and labeled jellybeans. When you identify a particular CRISPR of interest arrayed libraries, the CRISPR of interest is already labeled, therefore hit identification is much easier

Summer Diabetes Programs a Healthy Hit.

ERIC Educational Resources Information Center

Tribal College Journal, 2003

2003-01-01

Discusses whether it is possible for the AIHEC and tribal colleges to reverse poor eating habits and decrease diabetes rates for children through education. Students are gathered in a camp setting and they learn from scientists, nurses, nutritionists, biologists, and cultural teachers about how they can develop healthy habits. (MZ)

42 CFR 495.344 - Approval of the State Medicaid HIT plan, the HIT PAPD and update, the HIT IAPD and update, and...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Approval of the State Medicaid HIT plan, the HIT... Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Requirements Specific to the Medicaid Program § 495.344 Approval of the State Medicaid HIT plan, the HIT PAPD...

MYC/BCL2/BCL6 triple hit lymphoma: a study of 40 patients with a comparison to MYC/BCL2 and MYC/BCL6 double hit lymphomas.

PubMed

Huang, Wenting; Medeiros, L Jeffrey; Lin, Pei; Wang, Wei; Tang, Guilin; Khoury, Joseph; Konoplev, Sergej; Yin, C Cameron; Xu, Jie; Oki, Yasuhiro; Li, Shaoying

2018-05-21

High-grade B-cell lymphomas with MYC, BCL2, and BCL6 rearrangements (triple hit lymphoma) are uncommon. We studied the clinicopathologic features of 40 patients with triple hit lymphoma and compared them to 157 patients with MYC/BCL2 double hit lymphoma and 13 patients with MYC/BCL6 double hit lymphoma. The triple hit lymphoma group included 25 men and 15 women with a median age of 61 years (range, 34-85). Nine patients had a history of B-cell lymphoma. Histologically, 23 (58%) cases were diffuse large B-cell lymphoma and 17 cases had features of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Most cases of triple hit lymphoma were positive for CD10 (100%), BCL2 (95%), BCL6 (82%), MYC (74%), and 71% with MYC and BCL2 coexpression. P53 was overexpressed in 29% of triple hit lymphoma cases. The clinicopathological features of triple hit lymphoma patients were similar to patients with MYC/BCL2 and MYC/BCL6 double hit lymphoma, except that triple hit lymphoma cases were more often CD10 positive compared with MYC/BCL6 double hit lymphoma (p < 0.05). Induction chemotherapy used was similar for patients with triple hit lymphoma and double hit lymphoma and overall survival in triple hit lymphoma patients was 17.6 months, similar to the overall survival of patients with double hit lymphoma (p = 0.67). Patients with triple hit lymphoma showing P53 overexpression had significantly worse overall survival compared with those without P53 overexpression (p = 0.04). On the other hand, double expressor status and prior history of B-cell lymphoma did not correlate with overall survival. In conclusion, most patients with triple hit lymphoma have an aggressive clinical course and poor prognosis and these tumors have a germinal center B-cell immunophenotype, similar to patients with double hit lymphomas. P53 expression is a poor prognostic factor in patients with triple hit lymphoma.

Korean Immigrant Discipline and Children’s Social Competence and Behavior Problems

PubMed Central

Kim, Eunjung; Guo, Yuqing; Koh, Chinkang; Cain, Kevin C.

2009-01-01

The goal of this correlational study was to explore the relationship between Korean immigrant discipline (e.g., positive, appropriate, harsh discipline) and children’s social competence and behavior problems. Self-report data were collected from 58 mothers and 20 fathers of children aged from three and eight. Only paternal harsh discipline was positively correlated with children’s behavior problems. Among specific discipline strategies, maternal physical affection, correcting misbehaviors, and reasoning were positively correlated with children’s social competence. Paternal physical punishment (e.g., spanking, hitting, raising arms) was positively correlated with children’s behavior problems. Immigrant fathers need to learn alternative ways of managing children’s misbehaviors. PMID:21035016

Spontaneous heparin-induced thrombocytopenia (HIT) syndrome: HIT without any heparin exposure.

PubMed

Miyata, Shigeki

2016-01-01

Heparin-induced thrombocytopenia (HIT) is a pro-thrombotic side effect of heparin therapy caused by HIT antibodies with platelet-activating properties. Recent advances in understanding of spontaneous HIT syndrome, which can occur even without any heparin exposure despite its clinical and serological characteristics being similar to those of HIT, reveal the following HIT clinical features atypical for an immune-mediated disease. Heparin-naïve patients can develop IgG antibodies as early as day 4, as in a secondary immune response. Evidence for an anamnestic response upon heparin re-exposure is lacking. In addition, HIT antibodies are relatively short-lived, unlike those in a secondary immune response. Antigen immunoassays are commonly used worldwide for serological diagnosis of HIT. However, such assays do not indicate whether HIT antibodies have platelet-activating properties, leading to low diagnostic specificity for HIT. The detection of platelet-activating antibodies using a washed platelet activation assay is crucial for making a HIT diagnosis. These atypical clinical and serological features should be carefully considered while appropriately diagnosing HIT, which leads to appropriate therapy such as immediate administration of an alternative anticoagulant for preventing thromboembolic events and re-administration of heparin during surgery involving cardiopulmonary bypass when HIT antibodies are no longer detectable.

Non-alcoholic steatohepatitis: review of a growing medical problem.

PubMed

Te Sligte, K.; Bourass, I.; Sels, J.P.; Driessen, A.; Stockbrugger, R.W.; Koek, G.H.

2004-02-01

Non-alcoholic steatohepatitis (NASH) is a metabolic liver disorder that is seen in 2-6% of the general population. It manifests itself by elevated liver enzymes, frequently without symptoms. The histological findings include steatosis, inflammation, fibrosis, and cirrhosis. Three case reports are presented to illustrate features of NASH. A two-hit model has been proposed in the pathogenesis of NASH. The first hit is hepatic steatosis. A hypercaloric diet with high levels of carbohydrates and saturated fatty acids results in elevated plasma free fatty acids (FFA) and expands the adipose tissue. Insulin resistance develops and augments steatosis. Oxidation of FFA yields toxic free radicals, resulting in lipid peroxidation. They cause the second hits: increased oxidative stress on hepatocytes and induction of pro-inflammatory cytokines. When the antioxidant capacities of the liver are insufficient, mitochondrial dysfunction and tumor necrosis factor alpha (TNF-alpha) cause inflammation and fibrosis. Treatment consists of life style modifications, particularly weight loss and exercise. Many drugs have been tried in the treatment of NASH. The insulin-sensitizing drugs metformin, rosiglitazone, and pioglitazone, and the antioxidant vitamin E show promising results. Further investigation of therapeutic options is needed to direct the choice of therapy in the future.

A trace-driven analysis of name and attribute caching in a distributed system

NASA Technical Reports Server (NTRS)

Shirriff, Ken W.; Ousterhout, John K.

1992-01-01

This paper presents the results of simulating file name and attribute caching on client machines in a distributed file system. The simulation used trace data gathered on a network of about 40 workstations. Caching was found to be advantageous: a cache on each client containing just 10 directories had a 91 percent hit rate on name look ups. Entry-based name caches (holding individual directory entries) had poorer performance for several reasons, resulting in a maximum hit rate of about 83 percent. File attribute caching obtained a 90 percent hit rate with a cache on each machine of the attributes for 30 files. The simulations show that maintaining cache consistency between machines is not a significant problem; only 1 in 400 name component look ups required invalidation of a remotely cached entry. Process migration to remote machines had little effect on caching. Caching was less successful in heavily shared and modified directories such as /tmp, but there weren't enough references to /tmp overall to affect the results significantly. We estimate that adding name and attribute caching to the Sprite operating system could reduce server load by 36 percent and the number of network packets by 30 percent.

A new mutually reinforcing network node and link ranking algorithm

PubMed Central

Wang, Zhenghua; Dueñas-Osorio, Leonardo; Padgett, Jamie E.

2015-01-01

This study proposes a novel Normalized Wide network Ranking algorithm (NWRank) that has the advantage of ranking nodes and links of a network simultaneously. This algorithm combines the mutual reinforcement feature of Hypertext Induced Topic Selection (HITS) and the weight normalization feature of PageRank. Relative weights are assigned to links based on the degree of the adjacent neighbors and the Betweenness Centrality instead of assigning the same weight to every link as assumed in PageRank. Numerical experiment results show that NWRank performs consistently better than HITS, PageRank, eigenvector centrality, and edge betweenness from the perspective of network connectivity and approximate network flow, which is also supported by comparisons with the expensive N-1 benchmark removal criteria based on network efficiency. Furthermore, it can avoid some problems, such as the Tightly Knit Community effect, which exists in HITS. NWRank provides a new inexpensive way to rank nodes and links of a network, which has practical applications, particularly to prioritize resource allocation for upgrade of hierarchical and distributed networks, as well as to support decision making in the design of networks, where node and link importance depend on a balance of local and global integrity. PMID:26492958

A Distributed Cache Update Deployment Strategy in CDN

NASA Astrophysics Data System (ADS)

E, Xinhua; Zhu, Binjie

2018-04-01

The CDN management system distributes content objects to the edge of the internet to achieve the user's near access. Cache strategy is an important problem in network content distribution. A cache strategy was designed in which the content effective diffusion in the cache group, so more content was storage in the cache, and it improved the group hit rate.

Ranks of the Poor Swell with Women and Children.

ERIC Educational Resources Information Center

Connors, John H.

1987-01-01

The dramatic increase in poverty during the first half of the 1980s hit women and children the hardest. Regarding this fact, the following are discussed: (1) economic changes since 1960; (2) the extent of the problem; (3) reasons for the economic vulnerability of women and children; (4) curtailment of social services; and (5) probable future…

Sex Differences in Internalizing Problems during Adolescence in Autism Spectrum Disorder

ERIC Educational Resources Information Center

Oswald, Tasha M.; Winter-Messiers, Mary Ann; Gibson, Brandon; Schmidt, Alexandra M.; Herr, Cynthia M.; Solomon, Marjorie

2016-01-01

We hypothesized that the double hit conferred by sex and diagnosis increases the risk for internalizing disorders in adolescent females with autism spectrum disorder (ASD). In a sample of 32 adolescents with ASD and 32 controls, we examined the effects of sex, diagnostic factors, and developmental stages on depression and anxiety. A 3-way…

Batter's Choice and Differentiated Pitch Levels in Softball: A Student-Centered Approach

ERIC Educational Resources Information Center

Olsen, Edward B.

2015-01-01

Teaching youth softball presents several challenges to practitioners. Chief among these are the mixed ability levels, backgrounds and knowledge students have of certain games. The other problem is the "one size fits all" approach to pitching and hitting. In other words, many softball units allow for only one standard type of pitch…

Education in Austerity: Options for Planners. Fundamentals for Planning 36.

ERIC Educational Resources Information Center

Lewin, Keith M.

This book explores the issues raised by the changing climate within which educational planning will take place in the final years of the 20th century. The volume focuses on the problems faced by countries hardest hit by economic recession and the need for adjustment to a changing economic environment. Organized into six chapters, the book…

Training the Nation's Health Manpower.

ERIC Educational Resources Information Center

National Institutes of Health (DHEW), Bethesda, MD. Bureau of Health Manpower Education.

Over the past decade, there has been an increasing concern about the lack of health manpower to serve the U.S. population. The areas hardest hit by this shortage are the poverty areas in large cities and rural areas where 30% of the population but only 10% of the physicians live. Many Federal programs have begun to alleviate the problem of the…

Single ion hit detection set-up for the Zagreb ion microprobe

NASA Astrophysics Data System (ADS)

Smith, R. W.; Karlušić, M.; Jakšić, M.

2012-04-01

Irradiation of materials by heavy ions accelerated in MV tandem accelerators may lead to the production of latent ion tracks in many insulators and semiconductors. If irradiation is performed in a high resolution microprobe facility, ion tracks can be ordered by submicrometer positioning precision. However, full control of the ion track positioning can only be achieved by a reliable ion hit detection system that should provide a trigger signal irrespectively of the type and thickness of the material being irradiated. The most useful process that can be utilised for this purpose is emission of secondary electrons from the sample surface that follows the ion impact. The status report of the set-up presented here is based on the use of a channel electron multiplier (CEM) detector mounted on an interchangable sample holder that is inserted into the chamber in a close geometry along with the sample to be irradiated. The set-up has been tested at the Zagreb ion microprobe for different ions and energies, as well as different geometrical arrangements. For energies of heavy ions below 1 MeV/amu, results show that efficient (100%) control of ion impact can be achieved only for ions heavier than silicon. The successful use of the set-up is demonstrated by production of ordered single ion tracks in a polycarbonate film and by monitoring fluence during ion microbeam patterning of Foturan glass.

Performance of machine-learning scoring functions in structure-based virtual screening.

PubMed

Wójcikowski, Maciej; Ballester, Pedro J; Siedlecki, Pawel

2017-04-25

Classical scoring functions have reached a plateau in their performance in virtual screening and binding affinity prediction. Recently, machine-learning scoring functions trained on protein-ligand complexes have shown great promise in small tailored studies. They have also raised controversy, specifically concerning model overfitting and applicability to novel targets. Here we provide a new ready-to-use scoring function (RF-Score-VS) trained on 15 426 active and 893 897 inactive molecules docked to a set of 102 targets. We use the full DUD-E data sets along with three docking tools, five classical and three machine-learning scoring functions for model building and performance assessment. Our results show RF-Score-VS can substantially improve virtual screening performance: RF-Score-VS top 1% provides 55.6% hit rate, whereas that of Vina only 16.2% (for smaller percent the difference is even more encouraging: RF-Score-VS top 0.1% achieves 88.6% hit rate for 27.5% using Vina). In addition, RF-Score-VS provides much better prediction of measured binding affinity than Vina (Pearson correlation of 0.56 and -0.18, respectively). Lastly, we test RF-Score-VS on an independent test set from the DEKOIS benchmark and observed comparable results. We provide full data sets to facilitate further research in this area (http://github.com/oddt/rfscorevs) as well as ready-to-use RF-Score-VS (http://github.com/oddt/rfscorevs_binary).

An automatic microseismic or acoustic emission arrival identification scheme with deep recurrent neural networks

NASA Astrophysics Data System (ADS)

Zheng, Jing; Lu, Jiren; Peng, Suping; Jiang, Tianqi

2018-02-01

The conventional arrival pick-up algorithms cannot avoid the manual modification of the parameters for the simultaneous identification of multiple events under different signal-to-noise ratios (SNRs). Therefore, in order to automatically obtain the arrivals of multiple events with high precision under different SNRs, in this study an algorithm was proposed which had the ability to pick up the arrival of microseismic or acoustic emission events based on deep recurrent neural networks. The arrival identification was performed using two important steps, which included a training phase and a testing phase. The training process was mathematically modelled by deep recurrent neural networks using Long Short-Term Memory architecture. During the testing phase, the learned weights were utilized to identify the arrivals through the microseismic/acoustic emission data sets. The data sets were obtained by rock physics experiments of the acoustic emission. In order to obtain the data sets under different SNRs, this study added random noise to the raw experiments' data sets. The results showed that the outcome of the proposed method was able to attain an above 80 per cent hit-rate at SNR 0 dB, and an approximately 70 per cent hit-rate at SNR -5 dB, with an absolute error in 10 sampling points. These results indicated that the proposed method had high selection precision and robustness.

The Helicity Injected Torus (HIT) Program

NASA Astrophysics Data System (ADS)

Jarboe, T. R.; Gu, P.; Hamp, W.; Izzo, V.; Jewell, P.; Liptac, J.; McCollam, K. J.; Nelson, B. A.; Raman, R.; Redd, A. J.; Shumlak, U.; Sieck, P. E.; Smith, R. J.; Jain, K. K.; Nagata, M.; Uyama, T.

2000-10-01

The purpose of the Helicity Injected Torus (HIT) program is to develop current drive techniques for low-aspect-ratio toroidal plasmas. The present HIT-II spherical tokamak experiment is capable of both Coaxial Helicity Injection (CHI) and transformer action current drive. The HIT-II device itself is modestly sized (major radius R = 0.3 m, minor radius a = 0.2 m, with an on-axis magnetic field of up to Bo = 0.5 T), but has demonstrated toroidal plasma currents of up to 200 kA, using either CHI or transformer drive. An overview of ongoing research on HIT-II plasmas, including recent results, will be presented. An electron-locking model has been developed for helicity injection current drive; a description of this model will be presented, as well as comparisons to experimental results from the HIT and HIT-II devices. Empirical results from both the HIT program and past spheromak research, buttressed by theoretical developments, have led to the design of the upcoming HIT-SI (Helicity Injected Torus with Steady Inductive helicity injection) device (T.R. Jarboe, Fusion Technology 36, p. 85, 1999). HIT-SI will be able to form a high-beta spheromak, a low aspect ratio RFP or a spherical tokamak using constant inductive helicity injection. The HIT-SI design and construction progress will be presented.

Assessment of the performances of AcuStar HIT and the combination with heparin-induced multiple electrode aggregometry: a retrospective study.

PubMed

Minet, V; Bailly, N; Douxfils, J; Osselaer, J C; Laloy, J; Chatelain, C; Elalamy, I; Chatelain, B; Dogné, J M; Mullier, F

2013-09-01

Early diagnosis of immune heparin-induced thrombocytopenia (HIT) is challenging. HemosIL® AcuStar HIT and heparin-induced multiple electrode aggregometry (HIMEA) were recently proposed as rapid diagnostic methods. We conducted a study to assess performances of AcuStar HIT-IgG (PF4-H) and AcuStar HIT-Ab (PF4-H). The secondary objective was to compare the performances of the combination of Acustar HIT and HIMEA with standardised clinical diagnosis. Sera of 104 suspected HIT patients were retrospectively tested with AcuStar HIT. HIMEA was performed on available sera (n=81). The clinical diagnosis was established by analysing in a standardized manner the patient's medical records. These tests were also compared with PF4-Enhanced®, LTA, and SRA in subsets of patients. Thresholds were determined using ROC curve analysis with clinical outcome as reference. Using the recommended thresholds (1.00AU), the negative predictive value (NPV) of HIT-IgG and HIT-Ab were 100.0% (95% CI: 95.9%-100.0% and 95.7%-100.0%). The positive predictive value (PPV) were 64.3% (95% CI: 35.1%-87.2.2%) and 45.0% (95% CI: 23.2%-68.6%), respectively. Using our thresholds (HIT-IgG: 2.89AU, HIT-Ab: 9.41AU), NPV of HIT-IgG and HIT-Ab were 100.0% (95% CI: 96.0%-100.0% and 96.1%-100.0%). PPV were 75.0% (95% CI: 42.7%-94.5%) and 81.8% (95% CI: 48.3%-97.7%), respectively. Of the 79 patients with a medium-high pretest probability score, 67 were negative using HIT-IgG (PF4-H) test at our thresholds. HIMEA was performed on HIT-IgG positive patients. Using this combination, only one patient on 79 was incorrectly diagnosed. Acustar HIT showed good performances to exclude the diagnosis of HIT. Combination with HIMEA improves PPV. Copyright © 2013 Elsevier Ltd. All rights reserved.

Heparin-induced thrombocytopenia: real-world issues.

PubMed

Linkins, Lori-Ann; Warkentin, Theodore E

2011-09-01

Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by platelet-activating antibodies. HIT sera often activate platelets without needing heparin-such heparin-"independent" platelet activation can be associated with HIT beginning or worsening despite stopping heparin ("delayed-onset HIT"). We address important issues in HIT diagnosis and therapy, using a recent cohort of HIT patients to illustrate influences of heparin type; triggers for HIT investigation; serological features of heparin-independent platelet activation; and treatment. In our cohort of recent HIT cases ( N = 13), low-molecular-weight heparin (dalteparin) was a common causative agent ( N = 8, 62%); most patients were diagnosed after HIT-thrombosis had occurred; and danaparoid was the most frequently selected treatment. Heparin-independent platelet activation was common (7/13 [54%]) and predicted slower platelet count recovery (>1 week) among evaluable patients (5/5 vs 1/6; P = 0.015). In our experience with argatroban-treated patients, HIT-associated consumptive coagulopathy confounds anticoagulant monitoring. Our observations provide guidance on practical aspects of HIT diagnosis and management. Thieme Medical Publishers.

A Practical and Time-Efficient High-Intensity Interval Training Program Modifies Cardio-Metabolic Risk Factors in Adults with Risk Factors for Type II Diabetes.

PubMed

Phillips, Bethan E; Kelly, Benjamin M; Lilja, Mats; Ponce-González, Jesús Gustavo; Brogan, Robert J; Morris, David L; Gustafsson, Thomas; Kraus, William E; Atherton, Philip J; Vollaard, Niels B J; Rooyackers, Olav; Timmons, James A

2017-01-01

Regular physical activity (PA) can reduce the risk of developing type 2 diabetes, but adherence to time-orientated (150 min week -1 or more) PA guidelines is very poor. A practical and time-efficient PA regime that was equally efficacious at controlling risk factors for cardio-metabolic disease is one solution to this problem. Herein, we evaluate a new time-efficient and genuinely practical high-intensity interval training (HIT) protocol in men and women with pre-existing risk factors for type 2 diabetes. One hundred eighty-nine sedentary women ( n  = 101) and men ( n  = 88) with impaired glucose tolerance and/or a body mass index >27 kg m -2 [mean (range) age: 36 (18-53) years] participated in this multi-center study. Each completed a fully supervised 6-week HIT protocol at work-loads equivalent to ~100 or ~125% [Formula: see text]. Change in [Formula: see text] was used to monitor protocol efficacy, while Actiheart™ monitors were used to determine PA during four, weeklong, periods. Mean arterial (blood) pressure (MAP) and fasting insulin resistance [homeostatic model assessment (HOMA)-IR] represent key health biomarker outcomes. The higher intensity bouts (~125% [Formula: see text]) used during a 5-by-1 min HIT protocol resulted in a robust increase in [Formula: see text] (136 participants, +10.0%, p  < 0.001; large size effect). 5-by-1 HIT reduced MAP (~3%; p  < 0.001) and HOMA-IR (~16%; p  < 0.01). Physiological responses were similar in men and women while a sizeable proportion of the training-induced changes in [Formula: see text], MAP, and HOMA-IR was retained 3 weeks after cessation of training. The supervised HIT sessions accounted for the entire quantifiable increase in PA, and this equated to 400 metabolic equivalent (MET) min week -1 . Meta-analysis indicated that 5-by-1 HIT matched the efficacy and variability of a time-consuming 30-week PA program on [Formula: see text], MAP, and HOMA-IR. With a total time-commitment of <15 min per session and reliance on a practical ergometer protocol, 5-by-1 HIT offers a new solution to modulate cardio-metabolic risk factors in adults with pre-existing risk factors for type 2 diabetes while approximately meeting the MET min week -1 PA guidelines. Long-term randomized controlled studies will be required to quantify the ability for 5-by-1 HIT to reduce the incidence of type 2 diabetes, while strategies are required to harmonize the adaptations to exercise across individuals.

Hit identification and optimization in virtual screening: practical recommendations based on a critical literature analysis.

PubMed

Zhu, Tian; Cao, Shuyi; Su, Pin-Chih; Patel, Ram; Shah, Darshan; Chokshi, Heta B; Szukala, Richard; Johnson, Michael E; Hevener, Kirk E

2013-09-12

A critical analysis of virtual screening results published between 2007 and 2011 was performed. The activity of reported hit compounds from over 400 studies was compared to their hit identification criteria. Hit rates and ligand efficiencies were calculated to assist in these analyses, and the results were compared with factors such as the size of the virtual library and the number of compounds tested. A series of promiscuity, druglike, and ADMET filters were applied to the reported hits to assess the quality of compounds reported, and a careful analysis of a subset of the studies that presented hit optimization was performed. These data allowed us to make several practical recommendations with respect to selection of compounds for experimental testing, definition of hit identification criteria, and general virtual screening hit criteria to allow for realistic hit optimization. A key recommendation is the use of size-targeted ligand efficiency values as hit identification criteria.

Query-Adaptive Reciprocal Hash Tables for Nearest Neighbor Search.

PubMed

Liu, Xianglong; Deng, Cheng; Lang, Bo; Tao, Dacheng; Li, Xuelong

2016-02-01

Recent years have witnessed the success of binary hashing techniques in approximate nearest neighbor search. In practice, multiple hash tables are usually built using hashing to cover more desired results in the hit buckets of each table. However, rare work studies the unified approach to constructing multiple informative hash tables using any type of hashing algorithms. Meanwhile, for multiple table search, it also lacks of a generic query-adaptive and fine-grained ranking scheme that can alleviate the binary quantization loss suffered in the standard hashing techniques. To solve the above problems, in this paper, we first regard the table construction as a selection problem over a set of candidate hash functions. With the graph representation of the function set, we propose an efficient solution that sequentially applies normalized dominant set to finding the most informative and independent hash functions for each table. To further reduce the redundancy between tables, we explore the reciprocal hash tables in a boosting manner, where the hash function graph is updated with high weights emphasized on the misclassified neighbor pairs of previous hash tables. To refine the ranking of the retrieved buckets within a certain Hamming radius from the query, we propose a query-adaptive bitwise weighting scheme to enable fine-grained bucket ranking in each hash table, exploiting the discriminative power of its hash functions and their complement for nearest neighbor search. Moreover, we integrate such scheme into the multiple table search using a fast, yet reciprocal table lookup algorithm within the adaptive weighted Hamming radius. In this paper, both the construction method and the query-adaptive search method are general and compatible with different types of hashing algorithms using different feature spaces and/or parameter settings. Our extensive experiments on several large-scale benchmarks demonstrate that the proposed techniques can significantly outperform both the naive construction methods and the state-of-the-art hashing algorithms.

Computational Tools for the Identification and Interpretation of Sequence Motifs in Immunopeptidomes.

PubMed

Alvarez, Bruno; Barra, Carolina; Nielsen, Morten; Andreatta, Massimo

2018-01-12

Recent advances in proteomics and mass-spectrometry have widely expanded the detectable peptide repertoire presented by major histocompatibility complex (MHC) molecules on the cell surface, collectively known as the immunopeptidome. Finely characterizing the immunopeptidome brings about important basic insights into the mechanisms of antigen presentation, but can also reveal promising targets for vaccine development and cancer immunotherapy. This report describes a number of practical and efficient approaches to analyze immunopeptidomics data, discussing the identification of meaningful sequence motifs in various scenarios and considering current limitations. Guidelines are provided for the filtering of false hits and contaminants, and to address the problem of motif deconvolution in cell lines expressing multiple MHC alleles, both for the MHC class I and class II systems. Finally, it is demonstrated how machine learning can be readily employed by non-expert users to generate accurate prediction models directly from mass-spectrometry eluted ligand data sets. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enabling Large-Scale Design, Synthesis and Validation of Small Molecule Protein-Protein Antagonists

PubMed Central

Koes, David; Khoury, Kareem; Huang, Yijun; Wang, Wei; Bista, Michal; Popowicz, Grzegorz M.; Wolf, Siglinde; Holak, Tad A.; Dömling, Alexander; Camacho, Carlos J.

2012-01-01

Although there is no shortage of potential drug targets, there are only a handful known low-molecular-weight inhibitors of protein-protein interactions (PPIs). One problem is that current efforts are dominated by low-yield high-throughput screening, whose rigid framework is not suitable for the diverse chemotypes present in PPIs. Here, we developed a novel pharmacophore-based interactive screening technology that builds on the role anchor residues, or deeply buried hot spots, have in PPIs, and redesigns these entry points with anchor-biased virtual multicomponent reactions, delivering tens of millions of readily synthesizable novel compounds. Application of this approach to the MDM2/p53 cancer target led to high hit rates, resulting in a large and diverse set of confirmed inhibitors, and co-crystal structures validate the designed compounds. Our unique open-access technology promises to expand chemical space and the exploration of the human interactome by leveraging in-house small-scale assays and user-friendly chemistry to rationally design ligands for PPIs with known structure. PMID:22427896

Effectiveness Evaluation Method of Anti-Radiation Missile against Active Decoy

NASA Astrophysics Data System (ADS)

Tang, Junyao; Cao, Fei; Li, Sijia

2017-06-01

In the problem of anti-radiation missile against active decoy, whether the ARM can effectively kill the target radiation source and bait is an important index for evaluating the operational effectiveness of the missile. Aiming at this problem, this paper proposes a method to evaluate the effect of ARM against active decoy. Based on the calculation of ARM’s ability to resist the decoy, the paper proposes a method to evaluate the decoy resistance based on the key components of the hitting radar. The method has the advantages of scientific and reliability.

Making sense of health information technology implementation: A qualitative study protocol.

PubMed

Kitzmiller, Rebecca R; Anderson, Ruth A; McDaniel, Reuben R

2010-11-29

Implementing new practices, such as health information technology (HIT), is often difficult due to the disruption of the highly coordinated, interdependent processes (e.g., information exchange, communication, relationships) of providing care in hospitals. Thus, HIT implementation may occur slowly as staff members observe and make sense of unexpected disruptions in care. As a critical organizational function, sensemaking, defined as the social process of searching for answers and meaning which drive action, leads to unified understanding, learning, and effective problem solving -- strategies that studies have linked to successful change. Project teamwork is a change strategy increasingly used by hospitals that facilitates sensemaking by providing a formal mechanism for team members to share ideas, construct the meaning of events, and take next actions. In this longitudinal case study, we aim to examine project teams' sensemaking and action as the team prepares to implement new information technology in a tiertiary care hospital. Based on management and healthcare literature on HIT implementation and project teamwork, we chose sensemaking as an alternative to traditional models for understanding organizational change and teamwork. Our methods choices are derived from this conceptual framework. Data on project team interactions will be prospectively collected through direct observation and organizational document review. Through qualitative methods, we will identify sensemaking patterns and explore variation in sensemaking across teams. Participant demographics will be used to explore variation in sensemaking patterns. Outcomes of this research will be new knowledge about sensemaking patterns of project teams, such as: the antecedents and consequences of the ongoing, evolutionary, social process of implementing HIT; the internal and external factors that influence the project team, including team composition, team member interaction, and interaction between the project team and the larger organization; the ways in which internal and external factors influence project team processes; and the ways in which project team processes facilitate team task accomplishment. These findings will lead to new methods of implementing HIT in hospitals.

Making sense of health information technology implementation: A qualitative study protocol

PubMed Central

2010-01-01

Background Implementing new practices, such as health information technology (HIT), is often difficult due to the disruption of the highly coordinated, interdependent processes (e.g., information exchange, communication, relationships) of providing care in hospitals. Thus, HIT implementation may occur slowly as staff members observe and make sense of unexpected disruptions in care. As a critical organizational function, sensemaking, defined as the social process of searching for answers and meaning which drive action, leads to unified understanding, learning, and effective problem solving -- strategies that studies have linked to successful change. Project teamwork is a change strategy increasingly used by hospitals that facilitates sensemaking by providing a formal mechanism for team members to share ideas, construct the meaning of events, and take next actions. Methods In this longitudinal case study, we aim to examine project teams' sensemaking and action as the team prepares to implement new information technology in a tiertiary care hospital. Based on management and healthcare literature on HIT implementation and project teamwork, we chose sensemaking as an alternative to traditional models for understanding organizational change and teamwork. Our methods choices are derived from this conceptual framework. Data on project team interactions will be prospectively collected through direct observation and organizational document review. Through qualitative methods, we will identify sensemaking patterns and explore variation in sensemaking across teams. Participant demographics will be used to explore variation in sensemaking patterns. Discussion Outcomes of this research will be new knowledge about sensemaking patterns of project teams, such as: the antecedents and consequences of the ongoing, evolutionary, social process of implementing HIT; the internal and external factors that influence the project team, including team composition, team member interaction, and interaction between the project team and the larger organization; the ways in which internal and external factors influence project team processes; and the ways in which project team processes facilitate team task accomplishment. These findings will lead to new methods of implementing HIT in hospitals. PMID:21114860

Toward a Virus-Free Campus

ERIC Educational Resources Information Center

Silverstone, Ariel

2004-01-01

In academic settings, battling Internet threats and coming out unscathed is uncommon. Unfortunately, on many college campuses cyber-security concerns rarely extend beyond the IT staff and are addressed in a disparate, ad-hoc fashion. Yet, while many universities and large corporations were hit hard by the recent NetSky and Sasser worms, fewer than…

Women and Learning in the Iraqi War Zone

ERIC Educational Resources Information Center

Zangana, Haifa

2008-01-01

Having accumulated, throughout the twentieth century, historical achievements in education and standards of living higher than in most Arab and "third world" countries, Iraqi women were hit hard by two wars, the US-imposed economic sanctions of the 1990s, and then set back by the 2003 Anglo-American imperial occupation. Physical survival…

Skill Upgrading, Incorporated. Final Report.

ERIC Educational Resources Information Center

Skill Upgrading, Inc., Baltimore, MD.

As in two other projects in Cleveland and Newark, New Jersey, this project was set up in Baltimore to provide technical assistance in designing ways to meet in-plant skills needs by upgrading job skills on entry workers through High Intensity Training (HIT). Skill Upgrading, Inc. was established in Maryland to provide training and manpower…

Green Time for Screenagers

ERIC Educational Resources Information Center

Dillon, Robert

2011-01-01

For the past decade, schools throughout the United States have been working diligently to hit the targets set by national and state guidelines for academic achievement. Those targets have helped direct attention on the need to get all students achieving at a high level, but the laserlike focus on the target numbers have led many middle schools to…

77 FR 38634 - Request for Information: Collection and Use of Patient Work Information in the Clinical Setting...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-28

... inform health care. The Office of the National Coordinator (ONC) for Health Information Technology promotes a nationwide health information technology (HIT) infrastructure that allows for the electronic use... the `social history' section of an EMR? Where would you prefer patient work information to be stored...

A technology selection framework for supporting delivery of patient-oriented health interventions in developing countries

PubMed Central

Chan, Connie V.; Kaufman, David R.

2009-01-01

Health information technologies (HIT) have great potential to advance health care globally. In particular, HIT can provide innovative approaches and methodologies to overcome the range of access and resource barriers specific to developing countries. However, there is a paucity of models and empirical evidence informing the technology selection process in these settings. We propose a framework for selecting patient-oriented technologies in developing countries. The selection guidance process is structured by a set of filters that impose particular constraints and serve to narrow the space of possible decisions. The framework consists of three levels of factors: 1) situational factors, 2) the technology and its relationship with health interventions and with target patients, and 3) empirical evidence. We demonstrate the utility of the framework in the context of mobile phones for behavioral health interventions to reduce risk factors for cardiovascular disease. This framework can be applied to health interventions across health domains to explore how and whether available technologies can support delivery of the associated types of interventions and with the target populations. PMID:19796709

PepLine: a software pipeline for high-throughput direct mapping of tandem mass spectrometry data on genomic sequences.

PubMed

Ferro, Myriam; Tardif, Marianne; Reguer, Erwan; Cahuzac, Romain; Bruley, Christophe; Vermat, Thierry; Nugues, Estelle; Vigouroux, Marielle; Vandenbrouck, Yves; Garin, Jérôme; Viari, Alain

2008-05-01

PepLine is a fully automated software which maps MS/MS fragmentation spectra of trypsic peptides to genomic DNA sequences. The approach is based on Peptide Sequence Tags (PSTs) obtained from partial interpretation of QTOF MS/MS spectra (first module). PSTs are then mapped on the six-frame translations of genomic sequences (second module) giving hits. Hits are then clustered to detect potential coding regions (third module). Our work aimed at optimizing the algorithms of each component to allow the whole pipeline to proceed in a fully automated manner using raw nucleic acid sequences (i.e., genomes that have not been "reduced" to a database of ORFs or putative exons sequences). The whole pipeline was tested on controlled MS/MS spectra sets from standard proteins and from Arabidopsis thaliana envelope chloroplast samples. Our results demonstrate that PepLine competed with protein database searching softwares and was fast enough to potentially tackle large data sets and/or high size genomes. We also illustrate the potential of this approach for the detection of the intron/exon structure of genes.

The relevance of error analysis in graphical symbols evaluation.

PubMed

Piamonte, D P

1999-01-01

In an increasing number of modern tools and devices, small graphical symbols appear simultaneously in sets as parts of the human-machine interfaces. The presence of each symbol can influence the other's recognizability and correct association to its intended referents. Thus, aside from correct associations, it is equally important to perform certain error analysis of the wrong answers, misses, confusions, and even lack of answers. This research aimed to show how such error analyses could be valuable in evaluating graphical symbols especially across potentially different user groups. The study tested 3 sets of icons representing 7 videophone functions. The methods involved parameters such as hits, confusions, missing values, and misses. The association tests showed similar hit rates of most symbols across the majority of the participant groups. However, exploring the error patterns helped detect differences in the graphical symbols' performances between participant groups, which otherwise seemed to have similar levels of recognition. These are very valuable not only in determining the symbols to be retained, replaced or re-designed, but also in formulating instructions and other aids in learning to use new products faster and more satisfactorily.

First-passage and risk evaluation under stochastic volatility

NASA Astrophysics Data System (ADS)

Masoliver, Jaume; Perelló, Josep

2009-07-01

We solve the first-passage problem for the Heston random diffusion model. We obtain exact analytical expressions for the survival and the hitting probabilities to a given level of return. We study several asymptotic behaviors and obtain approximate forms of these probabilities which prove, among other interesting properties, the nonexistence of a mean-first-passage time. One significant result is the evidence of extreme deviations—which implies a high risk of default—when certain dimensionless parameter, related to the strength of the volatility fluctuations, increases. We confront the model with empirical daily data and we observe that it is able to capture a very broad domain of the hitting probability. We believe that this may provide an effective tool for risk control which can be readily applicable to real markets both for portfolio management and trading strategies.

Effects of low-volume high-intensity interval training (HIT) on fitness in adults: a meta-analysis of controlled and non-controlled trials.

PubMed

Weston, Matthew; Taylor, Kathryn L; Batterham, Alan M; Hopkins, Will G

2014-07-01

Low-volume high-intensity interval training (HIT) appears to be an efficient and practical way to develop physical fitness. Our objective was to estimate meta-analysed mean effects of HIT on aerobic power (maximum oxygen consumption [VO(2max)] in an incremental test) and sprint fitness (peak and mean power in a 30-s Wingate test). Five databases (PubMed, MEDLINE, Scopus, BIOSIS and Web of Science) were searched for original research articles published up to January 2014. Search terms included 'high intensity', 'HIT', 'sprint', 'fitness' and 'VO(2max)'. Inclusion criteria were fitness assessed pre- and post-training; training period ≥2 weeks; repetition duration 30-60 s; work/rest ratio <1.0; exercise intensity described as maximal or near maximal; adult subjects aged >18 years. The final data set consisted of 55 estimates from 32 trials for VO(2max), 23 estimates from 16 trials for peak sprint power, and 19 estimates from 12 trials for mean sprint power. Effects on fitness were analysed as percentages via log transformation. Standard errors calculated from exact p values (where reported) or imputed from errors of measurement provided appropriate weightings. Fixed effects in the meta-regression model included type of study (controlled, uncontrolled), subject characteristics (sex, training status, baseline fitness) and training parameters (number of training sessions, repetition duration, work/rest ratio). Probabilistic magnitude-based inferences for meta-analysed effects were based on standardized thresholds for small, moderate and large changes (0.2, 0.6 and 1.2, respectively) derived from between-subject standard deviations (SDs) for baseline fitness. A mean low-volume HIT protocol (13 training sessions, 0.16 work/rest ratio) in a controlled trial produced a likely moderate improvement in the VO(2max) of active non-athletic males (6.2 %; 90 % confidence limits ±3.1 %), when compared with control. There were possibly moderate improvements in the VO(2max) of sedentary males (10.0 %; ±5.1 %) and active non-athletic females (3.6 %; ±4.3 %) and a likely small increase for sedentary females (7.3 %; ±4.8 %). The effect on the VO(2max) of athletic males was unclear (2.7 %; ±4.6 %). A possibly moderate additional increase was likely for subjects with a 10 mL·kg(-1)·min(-1) lower baseline VO(2max) (3.8 %; ±2.5 %), whereas the modifying effects of sex and difference in exercise dose were unclear. The comparison of HIT with traditional endurance training was unclear (-1.6 %; ±4.3 %). Unexplained variation between studies was 2.0 % (SD). Meta-analysed effects of HIT on Wingate peak and mean power were unclear. Low-volume HIT produces moderate improvements in the aerobic power of active non-athletic and sedentary subjects. More studies are needed to resolve the unclear modifying effects of sex and HIT dose on aerobic power and the unclear effects on sprint fitness.

Maximizing the sensitivity and reliability of peptide identification in large-scale proteomic experiments by harnessing multiple search engines.

PubMed

Yu, Wen; Taylor, J Alex; Davis, Michael T; Bonilla, Leo E; Lee, Kimberly A; Auger, Paul L; Farnsworth, Chris C; Welcher, Andrew A; Patterson, Scott D

2010-03-01

Despite recent advances in qualitative proteomics, the automatic identification of peptides with optimal sensitivity and accuracy remains a difficult goal. To address this deficiency, a novel algorithm, Multiple Search Engines, Normalization and Consensus is described. The method employs six search engines and a re-scoring engine to search MS/MS spectra against protein and decoy sequences. After the peptide hits from each engine are normalized to error rates estimated from the decoy hits, peptide assignments are then deduced using a minimum consensus model. These assignments are produced in a series of progressively relaxed false-discovery rates, thus enabling a comprehensive interpretation of the data set. Additionally, the estimated false-discovery rate was found to have good concordance with the observed false-positive rate calculated from known identities. Benchmarking against standard proteins data sets (ISBv1, sPRG2006) and their published analysis, demonstrated that the Multiple Search Engines, Normalization and Consensus algorithm consistently achieved significantly higher sensitivity in peptide identifications, which led to increased or more robust protein identifications in all data sets compared with prior methods. The sensitivity and the false-positive rate of peptide identification exhibit an inverse-proportional and linear relationship with the number of participating search engines.

Novel 1,2-dihydroquinazolin-2-ones: Design, synthesis, and biological evaluation against Trypanosoma brucei.

PubMed

Pham, ThanhTruc; Walden, Madeline; Butler, Christopher; Diaz-Gonzalez, Rosario; Pérez-Moreno, Guiomar; Ceballos-Pérez, Gloria; Gomez-Pérez, Veronica; García-Hernández, Raquel; Zecca, Henry; Krakoff, Emma; Kopec, Brian; Ichire, Ogar; Mackenzie, Caden; Pitot, Marika; Ruiz, Luis Miguel; Gamarro, Francisco; González-Pacanowska, Dolores; Navarro, Miguel; Dounay, Amy B

2017-08-15

In 2014, a published report of the high-throughput screen of>42,000 kinase inhibitors from GlaxoSmithKline against T. brucei identified 797 potent and selective hits. From this rich data set, we selected NEU-0001101 (1) for hit-to-lead optimization. Through our preliminary compound synthesis and SAR studies, we have confirmed the previously reported activity of 1 in a T. brucei cell proliferation assay and have identified alternative groups to replace the pyridyl ring in 1. Pyrazole 24 achieves improvements in both potency and lipophilicity relative to 1, while also showing good in vitro metabolic stability. The SAR developed on 24 provides new directions for further optimization of this novel scaffold for anti-trypanosomal drug discovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

Strategies for the generation, validation and application of in silico ADMET models in lead generation and optimization.

PubMed

Gleeson, Matthew Paul; Montanari, Dino

2012-11-01

The most desirable chemical starting point in drug discovery is a hit or lead with a good overall profile, and where there may be issues; a clear SAR strategy should be identifiable to minimize the issue. Filtering based on drug-likeness concepts are a first step, but more accurate theoretical methods are needed to i) estimate the biological profile of molecule in question and ii) based on the underlying structure-activity relationships used by the model, estimate whether it is likely that the molecule in question can be altered to remove these liabilities. In this paper, the authors discuss the generation of ADMET models and their practical use in decision making. They discuss the issues surrounding data collation, experimental errors, the model assessment and validation steps, as well as the different types of descriptors and statistical models that can be used. This is followed by a discussion on how the model accuracy will dictate when and where it can be used in the drug discovery process. The authors also discuss how models can be developed to more effectively enable multiple parameter optimization. Models can be applied in lead generation and lead optimization steps to i) rank order a collection of hits, ii) prioritize the experimental assays needed for different hit series, iii) assess the likelihood of resolving a problem that might be present in a particular series in lead optimization and iv) screen a virtual library based on a hit or lead series to assess the impact of diverse structural changes on the predicted properties.

Hitting the Bull's-Eye: A Dart Game Simulation Using Graphing Calculator Technology

ERIC Educational Resources Information Center

Mittag, Kathleen Cage; Taylor, Sharon E.

2006-01-01

One problem that students have with mathematics is that they often view the topic as a series of unrelated ideas. Sometimes they are aware that they have to know one concept to move to the next, but what is done in geometry is not necessarily related to anything in algebra. This failure to recognize mathematical connections limits students'…

Beyond Marbles: Percent Change and Social Justice

ERIC Educational Resources Information Center

Denny, Flannery

2013-01-01

In the author's eighth year of teaching, she hit a wall teaching percent change. Percent change is one of the few calculations taught in math classes that shows up regularly in the media, and one that she often does in her head to make sense of the world around her. Despite this, she had been teaching percent change using textbook problems about…

Recession Rebound

ERIC Educational Resources Information Center

Weinstein, Margery

2011-01-01

A return to normal after a crisis is a good thing. Who doesn't want back what once seemed lost? The problem is it usually isn't a simple task figuring out how to patch together a scaled-back training program. When the recession hit in fall 2008, trainers were asked to scale down programming and make do with fewer resources. With a recovery in full…

Slow off the Mark: Elementary School Teachers and the Crisis in Science, Technology, Engineering, and Math Education

ERIC Educational Resources Information Center

Epstein, Diana; Miller, Raegen T.

2011-01-01

One can't throw a stone without hitting a STEM initiative these days, but most science, technology, engineering, and math initiatives--thus the STEM acronym--overlook a fundamental problem. In general, the workforce pipeline of elementary school teachers fails to ensure that the teachers who inform children's early academic trajectories have the…

Performance of a visuomotor walking task in an augmented reality training setting.

PubMed

Haarman, Juliet A M; Choi, Julia T; Buurke, Jaap H; Rietman, Johan S; Reenalda, Jasper

2017-12-01

Visual cues can be used to train walking patterns. Here, we studied the performance and learning capacities of healthy subjects executing a high-precision visuomotor walking task, in an augmented reality training set-up. A beamer was used to project visual stepping targets on the walking surface of an instrumented treadmill. Two speeds were used to manipulate task difficulty. All participants (n = 20) had to change their step length to hit visual stepping targets with a specific part of their foot, while walking on a treadmill over seven consecutive training blocks, each block composed of 100 stepping targets. Distance between stepping targets was varied between short, medium and long steps. Training blocks could either be composed of random stepping targets (no fixed sequence was present in the distance between the stepping targets) or sequenced stepping targets (repeating fixed sequence was present). Random training blocks were used to measure non-specific learning and sequenced training blocks were used to measure sequence-specific learning. Primary outcome measures were performance (% of correct hits), and learning effects (increase in performance over the training blocks: both sequence-specific and non-specific). Secondary outcome measures were the performance and stepping-error in relation to the step length (distance between stepping target). Subjects were able to score 76% and 54% at first try for lower speed (2.3 km/h) and higher speed (3.3 km/h) trials, respectively. Performance scores did not increase over the course of the trials, nor did the subjects show the ability to learn a sequenced walking task. Subjects were better able to hit targets while increasing their step length, compared to shortening it. In conclusion, augmented reality training by use of the current set-up was intuitive for the user. Suboptimal feedback presentation might have limited the learning effects of the subjects. Copyright © 2017 Elsevier B.V. All rights reserved.

Maximize, minimize or target - optimization for a fitted response from a designed experiment

DOE PAGES

Anderson-Cook, Christine Michaela; Cao, Yongtao; Lu, Lu

2016-04-01

One of the common goals of running and analyzing a designed experiment is to find a location in the design space that optimizes the response of interest. Depending on the goal of the experiment, we may seek to maximize or minimize the response, or set the process to hit a particular target value. After the designed experiment, a response model is fitted and the optimal settings of the input factors are obtained based on the estimated response model. Furthermore, the suggested optimal settings of the input factors are then used in the production environment.

Hit Identification and Optimization in Virtual Screening: Practical Recommendations Based Upon a Critical Literature Analysis

PubMed Central

Zhu, Tian; Cao, Shuyi; Su, Pin-Chih; Patel, Ram; Shah, Darshan; Chokshi, Heta B.; Szukala, Richard; Johnson, Michael E.; Hevener, Kirk E.

2013-01-01

A critical analysis of virtual screening results published between 2007 and 2011 was performed. The activity of reported hit compounds from over 400 studies was compared to their hit identification criteria. Hit rates and ligand efficiencies were calculated to assist in these analyses and the results were compared with factors such as the size of the virtual library and the number of compounds tested. A series of promiscuity, drug-like, and ADMET filters were applied to the reported hits to assess the quality of compounds reported and a careful analysis of a subset of the studies which presented hit optimization was performed. This data allowed us to make several practical recommendations with respect to selection of compounds for experimental testing, defining hit identification criteria, and general virtual screening hit criteria to allow for realistic hit optimization. A key recommendation is the use of size-targeted ligand efficiency values as hit identification criteria. PMID:23688234

The Helicity Injected Torus Program

NASA Astrophysics Data System (ADS)

Jarboe, T. R.; Nelson, B. A.; Jewell, P. D.; Liptac, J. E.; McCollam, K. J.; Raman, R.; Redd, A. J.; Rogers, J. A.; Sieck, P. E.; Shumlak, U.; Smith, R. J.; Nagata, M.; Uyama, T.

1999-11-01

The Helicity Injected Torus--II (HIT--II) spherical torus is capable of both Coaxial Helicity Injection (CHI) and transformer action current drive. HIT--II has a major radius R = 0.3, minor radius a = 0.2, aspect ratio A = R/a = 1.5, with an on axis magnetic field of up to Bo = 0.67 T. HIT--II provides equilibrium control, CHI flux boundary conditions, and transformer action using 28 poloidal field coils, using active flux feedback control. HIT--II has driven up to 200 kA of plasma current, using either CHI or transformer drive. An overview and recent results of the HIT--II program will be presented. The development of a locked-electron current drive model for HIT and HIT--II has led to the design of a constant inductive helicity injection method for spherical torii. This method is incorporated in the design of the Helicity Injected Torus -- Steady Inductive (HIT-- SI)(T.R. Jarboe, Fusion Technology, 36) (1), p. 85, 1999 experiment. HIT--SI can form a high-beta spheromak, a low aspect ratio RFP, or a spherical tokamak in a steady-state manner without using electrodes. The HIT--SI design and methodology will be presented.

TIM Barrel Protein Structure Classification Using Alignment Approach and Best Hit Strategy

NASA Astrophysics Data System (ADS)

Chu, Jia-Han; Lin, Chun Yuan; Chang, Cheng-Wen; Lee, Chihan; Yang, Yuh-Shyong; Tang, Chuan Yi

2007-11-01

The classification of protein structures is essential for their function determination in bioinformatics. It has been estimated that around 10% of all known enzymes have TIM barrel domains from the Structural Classification of Proteins (SCOP) database. With its high sequence variation and diverse functionalities, TIM barrel protein becomes to be an attractive target for protein engineering and for the evolution study. Hence, in this paper, an alignment approach with the best hit strategy is proposed to classify the TIM barrel protein structure in terms of superfamily and family levels in the SCOP. This work is also used to do the classification for class level in the Enzyme nomenclature (ENZYME) database. Two testing data sets, TIM40D and TIM95D, both are used to evaluate this approach. The resulting classification has an overall prediction accuracy rate of 90.3% for the superfamily level in the SCOP, 89.5% for the family level in the SCOP and 70.1% for the class level in the ENZYME. These results demonstrate that the alignment approach with the best hit strategy is a simple and viable method for the TIM barrel protein structure classification, even only has the amino acid sequences information.

Discovery of novel InhA reductase inhibitors: application of pharmacophore- and shape-based screening approach.

PubMed

Kumar, Uday Chandra; Bvs, Suneel Kumar; Mahmood, Shaik; D, Sriram; Kumar-Sahu, Prashanta; Pulakanam, Sridevi; Ballell, Lluís; Alvarez-Gomez, Daniel; Malik, Siddharth; Jarp, Sarma

2013-03-01

InhA is a promising and attractive target in antimycobacterial drug development. InhA is involved in the reduction of long-chain trans-2-enoyl-ACP in the type II fatty acid biosynthesis pathway of Mycobacterium tuberculosis. Recent studies have demonstrated that InhA is one of the targets for the second line antitubercular drug ethionamide. In the current study, we have generated quantitative pharmacophore models using known InhA inhibitors and validated using a large test set. The validated pharmacophore model was used as a query to screen an in-house database of 400,000 compounds and retrieved 25,000 hits. These hits were further ranked based on its shape and feature similarity with potent InhA inhibitor using rapid overlay of chemical structures (OpenEye™) and subsequent hits were subjected for docking. Based on the pharmacophore, rapid overlay of chemical structures model and docking interactions, 32 compounds with more than eight chemotypes were selected, purchased and assayed for InhA inhibitory activity. Out of the 32 compounds, 28 demonstrated 10-38% inhibition against InhA at 10 µM. Further optimization of these analogues is in progress and will update in due course.

NIMROD simulations and physics assessment of possible designs for a next generation Steady Inductive Helicity Injection HIT device

NASA Astrophysics Data System (ADS)

Penna, James; Morgan, Kyle; Grubb, Isaac; Jarboe, Thomas

2017-10-01

The Helicity Injected Torus - Steady Inductive 3 (HIT-SI3) experiment forms and maintains spheromaks via Steady Inductive Helicity Injection (SIHI) using discrete injectors that inject magnetic helicity via a non-axisymmetric perturbation and drive toroidally symmetric current. Newer designs for larger SIHI-driven spheromaks incorporate a set of injectors connected to a single external manifold to allow more freedom for the toroidal structure of the applied perturbation. Simulations have been carried out using the NIMROD code to assess the effectiveness of various imposed mode structures and injector schema in driving current via Imposed Dynamo Current Drive (IDCD). The results are presented here for varying flux conserver shapes on a device approximately 1.5 times larger than the current HIT-SI3 experiment. The imposed mode structures and spectra of simulated spheromaks are analyzed in order to examine magnetic structure and stability and determine an optimal regime for IDCD sustainment in a large device. The development of scaling laws for manifold operation is also presented, and simulation results are analyzed and assessed as part of the development path for the large scale device.

Rapid exclusion of the diagnosis of immune HIT by AcuStar HIT and heparin-induced multiple electrode aggregometry.

PubMed

Minet, V; Baudar, J; Bailly, N; Douxfils, J; Laloy, J; Lessire, S; Gourdin, M; Devalet, B; Chatelain, B; Dogné, J M; Mullier, F

2014-06-01

Accurate diagnosis of heparin-induced thrombocytopenia (HIT) is essential but remains challenging. We have previously demonstrated, in a retrospective study, the usefulness of the combination of the 4Ts score, AcuStar HIT and heparin-induced multiple electrode aggregometry (HIMEA) with optimized thresholds. We aimed at exploring prospectively the performances of our optimized diagnostic algorithm on suspected HIT patients. The secondary objective is to evaluate performances of AcuStar HIT-Ab (PF4-H) in comparison with the clinical outcome. 116 inpatients with clinically suspected immune HIT were included. Our optimized diagnostic algorithm was applied to each patient. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) of the overall diagnostic strategy as well as AcuStar HIT-Ab (at manufacturer's thresholds and at our thresholds) were calculated using clinical diagnosis as the reference. Among 116 patients, 2 patients had clinically-diagnosed HIT. These 2 patients were positive on AcuStar HIT-Ab, AcuStar HIT-IgG and HIMEA. Using our optimized algorithm, all patients were correctly diagnosed. AcuStar HIT-Ab at our cut-off (>9.41 U/mL) and at manufacturer's cut-off (>1.00 U/mL) showed both a sensitivity of 100.0% and a specificity of 99.1% and 90.4%, respectively. The combination of the 4Ts score, the HemosIL® AcuStar HIT and HIMEA with optimized thresholds may be useful for the rapid and accurate exclusion of the diagnosis of immune HIT. Copyright © 2014 Elsevier Ltd. All rights reserved.

Inappropriate documentation of heparin allergy in the medical record because of misdiagnosis of heparin-induced thrombocytopenia: frequency and consequences.

PubMed

McMahon, C M; Tanhehco, Y C; Cuker, A

2017-02-01

Essentials Misdiagnosis of heparin-induced thrombocytopenia (HIT) may be associated with adverse outcomes. We conducted a study of patients with a heparin allergy in the chart due to misdiagnosis of HIT. 42% of patients with a heparin allergy due to suspected HIT were clearly HIT-negative. 68% were unnecessarily treated with an alternative anticoagulant, 66% of whom had major bleeding. Background It is recommended that heparin be added to the allergy list of patients with heparin-induced thrombocytopenia (HIT). Misdiagnosis of HIT could lead to inappropriate documentation of a heparin allergy and adverse outcomes. Objectives To determine the frequency and consequences of inappropriate documentation of a heparin allergy because of misdiagnosis of HIT. Methods We conducted a cohort study of patients with an inappropriate heparin allergy listed in the electronic medical record (EMR) because of misdiagnosis of HIT. We searched the EMR for patients with a new heparin allergy. Patients were eligible if the reason for allergy listing was suspected acute HIT and laboratory testing for HIT was performed within 60 days. Subjects were defined as 'HIT-negative' if they had a 4Ts score of ≤ 3 or negative laboratory test results. Results Of 239 subjects with a new heparin allergy documented because of concern regarding HIT, 100 (42%) met the prespecified definition of HIT-negative. Sixty-eight (68%) HIT-negative subjects unnecessarily received an alternative parenteral anticoagulant for a median duration of 10.5 days. Among these 68 patients, 45 (66%) met criteria for major bleeding. Sixty-eight (68%) of the 100 HIT-negative subjects had an inappropriate allergy to heparin documented that persisted in the EMR for > 3 years beyond the index hospitalization. Conclusions Inappropriate listing of heparin as an allergy in the EMR because of misdiagnosis of HIT is common, is associated with substantial rates of unnecessary alternative anticoagulant use and major bleeding, and tends to persist beyond the index admission. © 2016 International Society on Thrombosis and Haemostasis.

Probabilistic sampling of protein conformations: new hope for brute force?

PubMed

Feldman, Howard J; Hogue, Christopher W V

2002-01-01

Protein structure prediction from sequence alone by "brute force" random methods is a computationally expensive problem. Estimates have suggested that it could take all the computers in the world longer than the age of the universe to compute the structure of a single 200-residue protein. Here we investigate the use of a faster version of our FOLDTRAJ probabilistic all-atom protein-structure-sampling algorithm. We have improved the method so that it is now over twenty times faster than originally reported, and capable of rapidly sampling conformational space without lattices. It uses geometrical constraints and a Leonard-Jones type potential for self-avoidance. We have also implemented a novel method to add secondary structure-prediction information to make protein-like amounts of secondary structure in sampled structures. In a set of 100,000 probabilistic conformers of 1VII, 1ENH, and 1PMC generated, the structures with smallest Calpha RMSD from native are 3.95, 5.12, and 5.95A, respectively. Expanding this test to a set of 17 distinct protein folds, we find that all-helical structures are "hit" by brute force more frequently than beta or mixed structures. For small helical proteins or very small non-helical ones, this approach should have a "hit" close enough to detect with a good scoring function in a pool of several million conformers. By fitting the distribution of RMSDs from the native state of each of the 17 sets of conformers to the extreme value distribution, we are able to estimate the size of conformational space for each. With a 0.5A RMSD cutoff, the number of conformers is roughly 2N where N is the number of residues in the protein. This is smaller than previous estimates, indicating an average of only two possible conformations per residue when sterics are accounted for. Our method reduces the effective number of conformations available at each residue by probabilistic bias, without requiring any particular discretization of residue conformational space, and is the fastest method of its kind. With computer speeds doubling every 18 months and parallel and distributed computing becoming more practical, the brute force approach to protein structure prediction may yet have some hope in the near future. Copyright 2001 Wiley-Liss, Inc.

77 FR 32639 - HIT Standards Committee and HIT Policy Committee; Call for Nominations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-01

... with the implementation of the Federal Health IT Strategic Plan, and in accordance with policies... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee and HIT Policy Committee; Call for... Health Information Technology Policy Committee (HITPC). Name of Committees: HIT Standards Committee and...

An Investigation of the Relationship Between Automated Machine Translation Evaluation Metrics and User Performance on an Information Extraction Task

DTIC Science & Technology

2007-01-01

parameter dimension between the two models). 93 were tested.3 Model 1 log( pHits 1− pHits ) = α + β1 ∗ MetricScore (6.6) The results for each of the...505.67 oTERavg .357 .13 .007 log( pHits 1− pHits ), that is, log-odds of correct task performance, of 2.79 over the intercept only model. All... pHits 1− pHits ) = −1.15− .418× I[MT=2] − .527× I[MT=3] + 1.78×METEOR+ 1.28×METEOR × I[MT=2] + 1.86×METEOR × I[MT=3] (6.7) Model 3 log( pHits 1− pHits

Review of Social and Organizational Issues in Health Information Technology.

PubMed

Kuziemsky, Craig E

2015-07-01

This paper reviews organizational and social issues (OSIs) in health information technology (HIT). A review and synthesis of the literature on OSIs in HIT was conducted. Five overarching themes with respect to OSIs in HIT were identified and discussed: scope and frameworks for defining OSIs in HIT, context matters, process immaturity and complexity, trade-offs will happen and need to be discussed openly, and means of studying OSIs in HIT. There is a wide body of literature that provides insight into OSIs in HIT, even if many of the studies are not explicitly labelled as such. The two biggest research needs are more explicit and theoretical studies of OSI in HITs and more research on integrating micro and macro perspectives of HIT use in organizations.

Identifying and Synchronizing Health Information Technology (HIT) Events from FDA Medical Device Reports.

PubMed

Kang, Hong; Wang, Frank; Zhou, Sicheng; Miao, Qi; Gong, Yang

2017-01-01

Health information technology (HIT) events, a subtype of patient safety events, pose a major threat and barrier toward a safer healthcare system. It is crucial to gain a better understanding of the nature of the errors and adverse events caused by current HIT systems. The scarcity of HIT event-exclusive databases and event reporting systems indicates the challenge of identifying the HIT events from existing resources. FDA Manufacturer and User Facility Device Experience (MAUDE) database is a potential resource for HIT events. However, the low proportion and the rapid evolvement of HIT-related events present challenges for distinguishing them from other equipment failures and hazards. We proposed a strategy to identify and synchronize HIT events from MAUDE by using a filter based on structured features and classifiers based on unstructured features. The strategy will help us develop and grow an HIT event-exclusive database, keeping pace with updates to MAUDE toward shared learning.

Multiple-hit parameter estimation in monolithic detectors.

PubMed

Hunter, William C J; Barrett, Harrison H; Lewellen, Tom K; Miyaoka, Robert S

2013-02-01

We examine a maximum-a-posteriori method for estimating the primary interaction position of gamma rays with multiple interaction sites (hits) in a monolithic detector. In assessing the performance of a multiple-hit estimator over that of a conventional one-hit estimator, we consider a few different detector and readout configurations of a 50-mm-wide square cerium-doped lutetium oxyorthosilicate block. For this study, we use simulated data from SCOUT, a Monte-Carlo tool for photon tracking and modeling scintillation- camera output. With this tool, we determine estimate bias and variance for a multiple-hit estimator and compare these with similar metrics for a one-hit maximum-likelihood estimator, which assumes full energy deposition in one hit. We also examine the effect of event filtering on these metrics; for this purpose, we use a likelihood threshold to reject signals that are not likely to have been produced under the assumed likelihood model. Depending on detector design, we observe a 1%-12% improvement of intrinsic resolution for a 1-or-2-hit estimator as compared with a 1-hit estimator. We also observe improved differentiation of photopeak events using a 1-or-2-hit estimator as compared with the 1-hit estimator; more than 6% of photopeak events that were rejected by likelihood filtering for the 1-hit estimator were accurately identified as photopeak events and positioned without loss of resolution by a 1-or-2-hit estimator; for PET, this equates to at least a 12% improvement in coincidence-detection efficiency with likelihood filtering applied.

Health Information Technologies-Academic and Commercial Evaluation (HIT-ACE) methodology: description and application to clinical feedback systems.

PubMed

Lyon, Aaron R; Lewis, Cara C; Melvin, Abigail; Boyd, Meredith; Nicodimos, Semret; Liu, Freda F; Jungbluth, Nathaniel

2016-09-22

Health information technologies (HIT) have become nearly ubiquitous in the contemporary healthcare landscape, but information about HIT development, functionality, and implementation readiness is frequently siloed. Theory-driven methods of compiling, evaluating, and integrating information from the academic and commercial sectors are necessary to guide stakeholder decision-making surrounding HIT adoption and to develop pragmatic HIT research agendas. This article presents the Health Information Technologies-Academic and Commercial Evaluation (HIT-ACE) methodology, a structured, theory-driven method for compiling and evaluating information from multiple sectors. As an example demonstration of the methodology, we apply HIT-ACE to mental and behavioral health measurement feedback systems (MFS). MFS are a specific class of HIT that support the implementation of routine outcome monitoring, an evidence-based practice. HIT-ACE is guided by theories and frameworks related to user-centered design and implementation science. The methodology involves four phases: (1) coding academic and commercial materials, (2) developer/purveyor interviews, (3) linking putative implementation mechanisms to hit capabilities, and (4) experimental testing of capabilities and mechanisms. In the current demonstration, phase 1 included a systematic process to identify MFS in mental and behavioral health using academic literature and commercial websites. Using user-centered design, implementation science, and feedback frameworks, the HIT-ACE coding system was developed, piloted, and used to review each identified system for the presence of 38 capabilities and 18 additional characteristics via a consensus coding process. Bibliometic data were also collected to examine the representation of the systems in the scientific literature. As an example, results are presented for the application of HIT-ACE phase 1 to MFS wherein 49 separate MFS were identified, reflecting a diverse array of characteristics and capabilities. Preliminary findings demonstrate the utility of HIT-ACE to represent the scope and diversity of a given class of HIT beyond what can be identified in the academic literature. Phase 2 data collection is expected to confirm and expand the information presented and phases 3 and 4 will provide more nuanced information about the impact of specific HIT capabilities. In all, HIT-ACE is expected to support adoption decisions and additional HIT development and implementation research.

Systematic Errors in Peptide and Protein Identification and Quantification by Modified Peptides*

PubMed Central

Bogdanow, Boris; Zauber, Henrik; Selbach, Matthias

2016-01-01

The principle of shotgun proteomics is to use peptide mass spectra in order to identify corresponding sequences in a protein database. The quality of peptide and protein identification and quantification critically depends on the sensitivity and specificity of this assignment process. Many peptides in proteomic samples carry biochemical modifications, and a large fraction of unassigned spectra arise from modified peptides. Spectra derived from modified peptides can erroneously be assigned to wrong amino acid sequences. However, the impact of this problem on proteomic data has not yet been investigated systematically. Here we use combinations of different database searches to show that modified peptides can be responsible for 20–50% of false positive identifications in deep proteomic data sets. These false positive hits are particularly problematic as they have significantly higher scores and higher intensities than other false positive matches. Furthermore, these wrong peptide assignments lead to hundreds of false protein identifications and systematic biases in protein quantification. We devise a “cleaned search” strategy to address this problem and show that this considerably improves the sensitivity and specificity of proteomic data. In summary, we show that modified peptides cause systematic errors in peptide and protein identification and quantification and should therefore be considered to further improve the quality of proteomic data annotation. PMID:27215553

Integration of research and practice to improve public health and healthcare delivery through a collaborative 'Health Integration Team' model - a qualitative investigation.

PubMed

Redwood, Sabi; Brangan, Emer; Leach, Verity; Horwood, Jeremy; Donovan, Jenny L

2016-06-22

Economic considerations and the requirement to ensure the quality, safety and integration of research with health and social care provision have given rise to local developments of collaborative organisational forms and strategies to span the translational gaps. One such model - the Health Integration Team (HIT) model in Bristol in the United Kingdom (UK) - brings together National Health Service (NHS) organisations, universities, local authorities, patients and the public to facilitate the systematic application of evidence to promote integration across healthcare pathways. This study aimed to (1) provide empirical evidence documenting the evolution of the model; (2) to identify the social and organisational processes and theory of change underlying healthcare knowledge and practice; and (3) elucidate the key aspects of the HIT model for future development and translation to other localities. Contemporaneous documents were analysed, using procedures associated with Framework Analysis to produce summarised data for descriptive accounts. In-depth interviews were undertaken with key informants and analysed thematically. Comparative methods were applied to further analyse the two data sets. One hundred forty documents were analysed and 10 interviews conducted with individuals in leadership positions in the universities, NHS commissioning and provider organisations involved in the design and implementation of the HIT model. Data coalesced around four overarching themes: 'Whole system' engagement, requiring the active recruitment of all those who have a stake in the area of practice being considered, and 'collaboration' to enable coproduction were identified as 'process' themes. System-level integration and innovation were identified as potential 'outcomes' with far-reaching impacts on population health and service delivery. The HIT model emerged as a particular response to the perceived need for integration of research and practice to improve public health and healthcare delivery at a time of considerable organisational turmoil and financial constraints. The concept gained momentum and will likely be of interest to those involved in setting up similar arrangements, and researchers in the social and implementation sciences with an interest in their evaluation.

Modular structure of functional networks in olfactory memory.

PubMed

Meunier, David; Fonlupt, Pierre; Saive, Anne-Lise; Plailly, Jane; Ravel, Nadine; Royet, Jean-Pierre

2014-07-15

Graph theory enables the study of systems by describing those systems as a set of nodes and edges. Graph theory has been widely applied to characterize the overall structure of data sets in the social, technological, and biological sciences, including neuroscience. Modular structure decomposition enables the definition of sub-networks whose components are gathered in the same module and work together closely, while working weakly with components from other modules. This processing is of interest for studying memory, a cognitive process that is widely distributed. We propose a new method to identify modular structure in task-related functional magnetic resonance imaging (fMRI) networks. The modular structure was obtained directly from correlation coefficients and thus retained information about both signs and weights. The method was applied to functional data acquired during a yes-no odor recognition memory task performed by young and elderly adults. Four response categories were explored: correct (Hit) and incorrect (False alarm, FA) recognition and correct and incorrect rejection. We extracted time series data for 36 areas as a function of response categories and age groups and calculated condition-based weighted correlation matrices. Overall, condition-based modular partitions were more homogeneous in young than elderly subjects. Using partition similarity-based statistics and a posteriori statistical analyses, we demonstrated that several areas, including the hippocampus, caudate nucleus, and anterior cingulate gyrus, belonged to the same module more frequently during Hit than during all other conditions. Modularity values were negatively correlated with memory scores in the Hit condition and positively correlated with bias scores (liberal/conservative attitude) in the Hit and FA conditions. We further demonstrated that the proportion of positive and negative links between areas of different modules (i.e., the proportion of correlated and anti-correlated areas) accounted for most of the observed differences in signed modularity. Taken together, our results provided some evidence that the neural networks involved in odor recognition memory are organized into modules and that these modular partitions are linked to behavioral performance and individual strategies. Copyright © 2014 Elsevier Inc. All rights reserved.

Evaluation of two new automated chemiluminescent assays (HemosIL® AcuStar HIT-IgG and HemosIL® AcuStar HIT-Ab) for the detection of heparin-induced antibodies in the diagnosis of heparin-induced thrombocytopenia.

PubMed

Van Hoecke, F; Devreese, K

2012-08-01

Recently, two new, fully automated quantitative chemiluminescent immunoassays, the HemosIL(®) AcuStar HIT-IgG (PF4-H), specific for IgG anti-PF4/H antibodies, and the HemosIL(®) AcuStar HIT-Ab(PF4-H), detecting IgG, IgM and IgA anti-PF4/H antibodies, were introduced into the market. In this study, their performance was compared mutually and with the Zymutest HIA IgG and HIA IgGAM ELISA. Citrated plasmas from 87 patients with clinical suspicion of heparin-induced thrombocytopenia (HIT) were analyzed with all four assays and with a functional confirmation assay. Apart from the manufacturer's cutoffs, optimalized cutoffs were evaluated as well. Sensitivities of all assays were 100%. The Acustar HIT-IgG assay showed a higher specificity compared with the HIT-Ab assay (85%vs. 73%), using the manufacturer's cutoffs. Specificities of all assays, except for the AcuStar HIT-IgG, could be significantly improved when altering the cutoff. Titers were significantly higher for the HIT-Ab assay compared with the HIT-IgG assay (P = 0.0001). This was also the case for the patients with confirmed HIT (P = 0.0495), indicating that the one cutoff (1.0 OD) for both Acustar assays, as proposed by the manufacturer, can be adapted for the AcuStar Hit-Ab assay resulting in an increased specificity. Performance characteristics of the Acustar HIT-IgG and HIT-Ab assay are comparable to the Zymutest HIA IgG and HIA IgGAM. © 2012 Blackwell Publishing Ltd.

Cerebral High-Intensity Transient Signals during Pediatric Cardiac Catheterization: A Pilot Study Using Transcranial Doppler Ultrasonography.

PubMed

LaRovere, Kerri L; Kapur, Kush; McElhinney, Doff B; Razumovsky, Alexander; Kussman, Barry D

2017-07-01

Cerebral emboli are one potential cause of acute brain injury in children with congenital heart disease (CHD) undergoing cardiac catheterization. In this pilot study using transcranial Doppler (TCD) ultrasonography, we sought to evaluate the incidence, burden, and circumstances of cerebral high-intensity transient signals (HITS), presumably representing emboli, during pediatric cardiac catheterization. Emboli monitoring of the right middle cerebral artery was performed in five children. HITS, counted offline, were defined as unidirectional signals associated with audible "chirp" and sinusoidal correlation. HITS were grouped as single, >10 HITS ("cluster"), or HITS "with curtain effect" per 3-5 cardiac cycles. Cerebral blood flow velocity (CBFV) and pulsatility index (PI) were recorded after anesthetic induction (baseline). Total HITS in the cohort was 1,697 (790 single HITS, 606 HITS within clusters, and 301 HITS within curtains). HITS in clusters and curtains comprised 53% (907/1,697) of total HITS, and occurred in 44 clusters/curtains. Events associated with clusters/curtains included left ventricular angiography (39%; 17/44), right ventricular angiography (16%; 7/44), device placement (16%; 7/44), heparin bolus (9%; 4/44), pulmonary artery angiography (9%; 4/44), venous access (5%; 2/44), right atrial angiography (2%; 1/44), arterial access (2%; 1/44), and hemodynamic measurements (2%; 1/44). No patient had clinically detectable neurologic injury. HITS are common during pediatric cardiac catheterization, and associated with procedural factors. Whether curtains/clusters are worse than single, repetitive HITS is unknown. Larger studies are needed to determine whether HITS are a marker of risk of neurologic injury from emboli during pediatric cardiac catheterization. Copyright © 2017 by the American Society of Neuroimaging.

Platelet count recovery and seroreversion in immune HIT despite continuation of heparin: further observations and literature review.

PubMed

Shih, Andrew W; Sheppard, Jo-Ann I; Warkentin, Theodore E

2017-10-05

One of the standard distinctions between type 1 (non-immune) and type 2 (immune-mediated) heparin-induced thrombocytopenia (HIT) is the transience of thrombocytopenia: type 1 HIT is viewed as early-onset and transient thrombocytopenia, with platelet count recovery despite continuing heparin administration. In contrast, type 2 HIT is viewed as later-onset (i. e., 5 days or later) thrombocytopenia in which it is generally believed that platelet count recovery will not occur unless heparin is discontinued. However, older reports of type 2 HIT sometimes did include the unexpected observation that platelet counts could recover despite continued heparin administration, although without information provided regarding changes in HIT antibody levels in association with platelet count recovery. In recent years, some reports of type 2 HIT have confirmed the observation that platelet count recovery can occur despite continuing heparin administration, with serological evidence of waning levels of HIT antibodies ("seroreversion"). We now report two additional patient cases of type 2 HIT with platelet count recovery despite ongoing therapeutic-dose (1 case) or prophylactic-dose (1 case) heparin administration, in which we demonstrate concomitant waning of HIT antibody levels. We further review the literature describing this phenomenon of HIT antibody seroreversion and platelet count recovery despite continuing heparin administration. Our observations add to the concept that HIT represents a remarkably transient immune response, including sometimes even when heparin is continued.

Novel HIT antibody detection method using Sonoclot® coagulation analyzer.

PubMed

Wanaka, Keiko; Asada, Reiko; Miyashita, Kumiko; Kaneko, Makoto; Endo, Hirokazu; Yatomi, Yutaka

2015-01-01

Since heparin-induced thrombocytopenia (HIT), caused by the generation of antibodies against platelet factor 4 (PF4)/heparin complexes (HIT antibodies), may induce serious complications due to thrombosis, a prompt diagnosis is desirable. Functional tests with platelet activation to detect HIT antibodies are useful for diagnosis of HIT, in particular (14)C-selotonin release assay (SRA). However, they are complicated and so can be performed only in limited laboratories. We tested if a blood coagulation test using Sonoclot® analyzer can serve for the detection of HIT antibodies. A murine monoclonal antibody (HIT-MoAb) against PF4/heparin complexes was used as an alternative to human HIT antibodies. To the mixture of HIT-MoAb and heparin (0.5 U/mL, final), whole blood obtained from a healthy volunteer was added, and then the activated clotting time (ACT), clot rate (CR), and area under the curve (AUC) were measured with Sonoclot® analyzer for 30minutes. The HIT-MoAb (30 to 100μg/mL, final) concentration dependently suppressed the anticoagulation activity (prolongation of ACT and decrease of CR and AUC) of heparin. The suppression of anticoagulation effect of heparin by HIT-MoAb was demonstrated by measurements using Sonoclot® analyzer. This method may provide a new tool for screening of HIT antibodies. Copyright © 2014 Elsevier Ltd. All rights reserved.

web cellHTS2: a web-application for the analysis of high-throughput screening data.

PubMed

Pelz, Oliver; Gilsdorf, Moritz; Boutros, Michael

2010-04-12

The analysis of high-throughput screening data sets is an expanding field in bioinformatics. High-throughput screens by RNAi generate large primary data sets which need to be analyzed and annotated to identify relevant phenotypic hits. Large-scale RNAi screens are frequently used to identify novel factors that influence a broad range of cellular processes, including signaling pathway activity, cell proliferation, and host cell infection. Here, we present a web-based application utility for the end-to-end analysis of large cell-based screening experiments by cellHTS2. The software guides the user through the configuration steps that are required for the analysis of single or multi-channel experiments. The web-application provides options for various standardization and normalization methods, annotation of data sets and a comprehensive HTML report of the screening data analysis, including a ranked hit list. Sessions can be saved and restored for later re-analysis. The web frontend for the cellHTS2 R/Bioconductor package interacts with it through an R-server implementation that enables highly parallel analysis of screening data sets. web cellHTS2 further provides a file import and configuration module for common file formats. The implemented web-application facilitates the analysis of high-throughput data sets and provides a user-friendly interface. web cellHTS2 is accessible online at http://web-cellHTS2.dkfz.de. A standalone version as a virtual appliance and source code for platforms supporting Java 1.5.0 can be downloaded from the web cellHTS2 page. web cellHTS2 is freely distributed under GPL.

An empirically-derived approach for investigating Health Information Technology: the Elementally Entangled Organisational Communication (EEOC) framework.

PubMed

Georgiou, Andrew; Westbrook, Johanna I; Braithwaite, Jeffrey

2012-07-12

The purpose of this paper is to illustrate the Elementally Entangled Organisational Communication (EEOC) framework by drawing on a set of three case studies which assessed the impact of new Health Information Technology (HIT) on a pathology service. The EEOC framework was empirically developed as a tool to tackle organisational communication challenges in the implementation and evaluation of health information systems. The framework was synthesised from multiple research studies undertaken across a major metropolitan hospital pathology service during the period 2005 to 2008. These studies evaluated the impact of new HIT systems in pathology departments (Laboratory Information System) and an Emergency Department (Computerised Provider Order Entry) located in Sydney, Australia. Key dimensions of EEOC are illustrated by the following case studies: 1) the communication infrastructure between the Blood Bank and the ward for the coordination and distribution of blood products; 2) the organisational environment in the Clinical Chemistry and Haematology departments and their attempts to organise, plan and control the processing of laboratory specimens; and 3) the temporal make up of the organisation as revealed in changes to the way the Central Specimen Reception allocated, sequenced and synchronised work tasks. The case studies not only highlight the pre-existing communication architecture within the organisation but also the constitutive role communication plays in the way organisations go about addressing their requirements. HIT implementation involves a mutual transformation of the organisation and the technology. This is a vital consideration because of the dangers associated with poor organisational planning and implementation of HIT, and the potential for unintended adverse consequences, workarounds and risks to the quality and safety of patient care. The EEOC framework aims to account for the complex range of contextual factors and triggers that play a role in the success or otherwise of new HITs, and in the realisation of their innovation potential.

An empirically-derived approach for investigating Health Information Technology: the Elementally Entangled Organisational Communication (EEOC) framework

PubMed Central

2012-01-01

Background The purpose of this paper is to illustrate the Elementally Entangled Organisational Communication (EEOC) framework by drawing on a set of three case studies which assessed the impact of new Health Information Technology (HIT) on a pathology service. The EEOC framework was empirically developed as a tool to tackle organisational communication challenges in the implementation and evaluation of health information systems. Methods The framework was synthesised from multiple research studies undertaken across a major metropolitan hospital pathology service during the period 2005 to 2008. These studies evaluated the impact of new HIT systems in pathology departments (Laboratory Information System) and an Emergency Department (Computerised Provider Order Entry) located in Sydney, Australia. Results Key dimensions of EEOC are illustrated by the following case studies: 1) the communication infrastructure between the Blood Bank and the ward for the coordination and distribution of blood products; 2) the organisational environment in the Clinical Chemistry and Haematology departments and their attempts to organise, plan and control the processing of laboratory specimens; and 3) the temporal make up of the organisation as revealed in changes to the way the Central Specimen Reception allocated, sequenced and synchronised work tasks. Conclusions The case studies not only highlight the pre-existing communication architecture within the organisation but also the constitutive role communication plays in the way organisations go about addressing their requirements. HIT implementation involves a mutual transformation of the organisation and the technology. This is a vital consideration because of the dangers associated with poor organisational planning and implementation of HIT, and the potential for unintended adverse consequences, workarounds and risks to the quality and safety of patient care. The EEOC framework aims to account for the complex range of contextual factors and triggers that play a role in the success or otherwise of new HITs, and in the realisation of their innovation potential. PMID:22788698

Power of Orbitrap-based LC-high resolution-MS/MS for comprehensive drug testing in urine with or without conjugate cleavage or using dried urine spots after on-spot cleavage in comparison to established LC-MSn or GC-MS procedures.

PubMed

Michely, Julian A; Meyer, Markus R; Maurer, Hans H

2018-01-01

Reliable, sensitive, and comprehensive urine screening procedures by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS) with low or high resolution (HR) are of high importance for drug testing, adherence monitoring, or detection of toxic compounds. Besides conventional urine sampling, dried urine spots are of increasing interest. In the present study, the power of LC-HR-MS/MS was investigated for comprehensive drug testing in urine with or without conjugate cleavage or using dried urine spots after on-spot cleavage in comparison to established LC-MS n or GC-MS procedures. Authentic human urine samples (n = 103) were split in 4 parts. One aliquot was prepared by precipitation (UP), one by UP with conjugate cleavage (UglucP), one spot on filter paper cards and prepared by on-spot cleavage followed by liquid extraction (DUSglucE), and one worked-up by acid hydrolysis, liquid-liquid extraction, and acetylation for GC-MS analysis. The 3 series of LC-HR-MS/MS results were compared among themselves, to corresponding published LC-MS n data, and to screening results obtained by conventional GC-MS. The reference libraries used for the 3 techniques contained over 4500 spectra of parent compounds and their metabolites. The number of all detected hits (770 drug intakes) was set to 100%. The LC-HR-MS/MS approach detected 80% of the hits after UP, 89% after UglucP, and 77% after DUSglucE, which meant over one-third more hits in comparison to the corresponding published LC-MS n results with ≤49% detected hits. The GC-MS approach identified 56% of all detected hits. In conclusion, LC-HR-MS/MS provided the best screening results after conjugate cleavage and precipitation. Copyright © 2017 John Wiley & Sons, Ltd.

Exploring what motivates and sustains support group engagement amongst young people with allergies: a qualitative study.

PubMed

Jones, Christina J; Sommereux, Lauren A; Smith, Helen E

2018-06-14

Positive self-care behaviours are more likely in young people who engage with allergy support groups, but reasons for this association are not well understood. This study explored how and why young people engage with allergy support groups to identify what activities and resources are beneficial. In-depth, semi-structured interviews were conducted with young people aged 12-21 years who reported engaging with allergy support groups (in person or on-line). Interviews were audiotaped, transcribed verbatim and analysed using thematic content analysis. The 21 participants had a range of allergies; initially most joined support groups on suggestion of their parent/carer although older participants sought groups independently. Feeling included and sharing experiences with people with similar problems/challenges were highly valued. Through membership, young people reported improved self-esteem and confidence in both managing their allergies and lives generally. Information, such as allergy alerts and hard-hitting video campaigns were reported to positively influence adherence to self-care behaviours such as carrying medication which led to sustained engagement. Participants wanted greater availability of allergy support groups, and higher profiles in healthcare and educational settings, as well as through social media. Participants valued the psychological and practical support of networking with others with allergies, and described how membership improved their confidence. This study also provides insight into the ways support groups improve young people's adherence to medical advice and positive self-care behaviours; participants responded well to hard-hitting video campaigns which appeared to emphasise the severity and susceptibility of anaphylaxis. Participants identified the need for more active promotion of support groups amongst young people and their clinicians, as well as making them available in more localities. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A model to predict when a cholera outbreak might hit the Congo

NASA Astrophysics Data System (ADS)

Schultz, Colin

2014-09-01

In 2011, as many as 600,000 people in 58 countries contracted cholera, with thousands succumbing to the disease. In most countries, cholera is rare. In others, like the Democratic Republic of the Congo, cholera is an endemic threat, always lurking in the background waiting for the right set of conditions to spark an outbreak.

Hitting a High Note on Math Tests: Remembered Success Influences Test Preferences

ERIC Educational Resources Information Center

Finn, Bridgid; Miele, David B.

2016-01-01

Remembered utility is the retrospective evaluation about the pleasure and pain associated with a past experience. It can influence choices about repeating or avoiding similar situations in the future (Kahneman, 2000). A set of 5 experiments explored the remembered utility of effortful test episodes and how it impacted future test choices.…

Tiger Moms and the Model Minority Myth

ERIC Educational Resources Information Center

Gym, Helen

2011-01-01

Some months ago, Yale law professor Amy Chua wrote an op-ed for the "Wall Street Journal" that set off a media and cultural firestorm. Titled "Why Chinese Mothers Are Superior," the piece's outlandish assertions about Asian immigrant parenting hit the requisite rounds on the 24-hour news cycle. Though the media chatter was nonstop for weeks, what…

Fall Prevention Hits Stumbling Blocks.

PubMed

Huff, Charlotte

2018-03-01

Implementation of efforts to screen older people for fall risk-and to intervene before falls occur-have been scattershot at best. Ongoing studies of fall prevention called STRIDE (Strategies to Reduce Injuries and Develop Confidence in Elders) might change that. The studies look at whether clinicians can implement a fall-prevention program across rural, urban, and suburban treatment settings.

The Influence of a High Intensity Physical Activity Intervention on a Selection of Health Related Outcomes: An Ecological Approach

ClinicalTrials.gov

2009-12-04

To Assess the Impact of the HIT Intervention on Physiological Responses; To Assess the Role of a Secondary High School as a Setting for Promoting Healthy Eating and PA Behaviours; To Determine the Associations Between CVD Risk Factors at Baseline in 15 - 18 Year Old Youth

Review of Social and Organizational Issues in Health Information Technology

PubMed Central

2015-01-01

Objectives This paper reviews organizational and social issues (OSIs) in health information technology (HIT). Methods A review and synthesis of the literature on OSIs in HIT was conducted. Results Five overarching themes with respect to OSIs in HIT were identified and discussed: scope and frameworks for defining OSIs in HIT, context matters, process immaturity and complexity, trade-offs will happen and need to be discussed openly, and means of studying OSIs in HIT. Conclusions There is a wide body of literature that provides insight into OSIs in HIT, even if many of the studies are not explicitly labelled as such. The two biggest research needs are more explicit and theoretical studies of OSI in HITs and more research on integrating micro and macro perspectives of HIT use in organizations. PMID:26279951

In silico and in vitro screening to identify structurally diverse non-azole CYP51 inhibitors as potent antifungal agent.

PubMed

Singh, Aarti; Paliwal, Sarvesh Kumar; Sharma, Mukta; Mittal, Anupama; Sharma, Swapnil; Sharma, Jai Prakash

2016-01-01

The problem of resistance to azole class of antifungals is a serious cause of concern to the medical fraternity and thus there is an urgent need to identify non-azole scaffolds with high affinity for lanosterol 14α-demethylase (CYP51). In view of this we have attempted to identify novel non-azole CYP51 inhibitors through the application of pharmacophore based virtual screening and in vitro evaluation. A rigorously validated pharmacophore model comprising of 2 hydrogen bond acceptor and 2 hydrophobic features has been developed and used to mine NCI database. Out of 265 retrieved hits, NSC 1215 and 1520 have been chosen on the basis of Lipinski's rule of five, fit and estimated values. Both the hits were docked into the active site of CYP51. In view of high fit value and CDocker score, NSC 1215 and 1520 have been subjected to in vitro microbiological assay. The result reveals that NSC 1215 and 1520 are active against Candida albicans, Candida parapsilosis, Candida tropicalis, and Aspergillus niger. In addition to this the absorption characteristics of both the hits have also been determined using the rat sac technique and permeation in order of NSC 1520>NSC 1215 has been observed. Copyright © 2015 Elsevier Inc. All rights reserved.

Optimizing homeostatic cell renewal in hierarchical tissues

PubMed Central

Fider, Nicole A.

2018-01-01

In order to maintain homeostasis, mature cells removed from the top compartment of hierarchical tissues have to be replenished by means of differentiation and self-renewal events happening in the more primitive compartments. As each cell division is associated with a risk of mutation, cell division patterns have to be optimized, in order to minimize or delay the risk of malignancy generation. Here we study this optimization problem, focusing on the role of division tree length, that is, the number of layers of cells activated in response to the loss of terminally differentiated cells, which is related to the balance between differentiation and self-renewal events in the compartments. Using both analytical methods and stochastic simulations in a metapopulation-style model, we find that shorter division trees are advantageous if the objective is to minimize the total number of one-hit mutants in the cell population. Longer division trees on the other hand minimize the accumulation of two-hit mutants, which is a more likely evolutionary goal given the key role played by tumor suppressor genes in cancer initiation. While division tree length is the most important property determining mutant accumulation, we also find that increasing the size of primitive compartments helps to delay two-hit mutant generation. PMID:29447149

Identification of Trypanocidal Activity for Known Clinical Compounds Using a New Trypanosoma cruzi Hit-Discovery Screening Cascade.

PubMed

De Rycker, Manu; Thomas, John; Riley, Jennifer; Brough, Stephen J; Miles, Tim J; Gray, David W

2016-04-01

Chagas disease is a significant health problem in Latin America and the available treatments have significant issues in terms of toxicity and efficacy. There is thus an urgent need to develop new treatments either via a repurposing strategy or through the development of new chemical entities. A key first step is the identification of compounds with anti-Trypanosoma cruzi activity from compound libraries. Here we describe a hit discovery screening cascade designed to specifically identify hits that have the appropriate anti-parasitic properties to warrant further development. The cascade consists of a primary imaging-based assay followed by newly developed and appropriately scaled secondary assays to predict the cidality and rate-of-kill of the compounds. Finally, we incorporated a cytochrome P450 CYP51 biochemical assay to remove compounds that owe their phenotypic response to inhibition of this enzyme. We report the use of the cascade in profiling two small libraries containing clinically tested compounds and identify Clemastine, Azelastine, Ifenprodil, Ziprasidone and Clofibrate as molecules having appropriate profiles. Analysis of clinical derived pharmacokinetic and toxicity data indicates that none of these are appropriate for repurposing but they may represent suitable start points for further optimisation for the treatment of Chagas disease.

Structure-kinetic relationships--an overlooked parameter in hit-to-lead optimization: a case of cyclopentylamines as chemokine receptor 2 antagonists.

PubMed

Vilums, Maris; Zweemer, Annelien J M; Yu, Zhiyi; de Vries, Henk; Hillger, Julia M; Wapenaar, Hannah; Bollen, Ilse A E; Barmare, Farhana; Gross, Raymond; Clemens, Jeremy; Krenitsky, Paul; Brussee, Johannes; Stamos, Dean; Saunders, John; Heitman, Laura H; Ijzerman, Adriaan P

2013-10-10

Preclinical models of inflammatory diseases (e.g., neuropathic pain, rheumatoid arthritis, and multiple sclerosis) have pointed to a critical role of the chemokine receptor 2 (CCR2) and chemokine ligand 2 (CCL2). However, one of the biggest problems of high-affinity inhibitors of CCR2 is their lack of efficacy in clinical trials. We report a new approach for the design of high-affinity and long-residence-time CCR2 antagonists. We developed a new competition association assay for CCR2, which allows us to investigate the relation of the structure of the ligand and its receptor residence time [i.e., structure-kinetic relationship (SKR)] next to a traditional structure-affinity relationship (SAR). By applying combined knowledge of SAR and SKR, we were able to re-evaluate the hit-to-lead process of cyclopentylamines as CCR2 antagonists. Affinity-based optimization yielded compound 1 with good binding (Ki = 6.8 nM) but very short residence time (2.4 min). However, when the optimization was also based on residence time, the hit-to-lead process yielded compound 22a, a new high-affinity CCR2 antagonist (3.6 nM), with a residence time of 135 min.

A comparison of the double hydrodistention implantation technique (HIT) and the HIT with a polyacrylate/polyalcohol copolymer (PPC) for the endoscopic treatment of primary vesicoureteral reflux.

PubMed

Akin, Melih; Erginel, Basak; Karadag, Cetin Ali; Yildiz, Abdullah; Ozçelik, Gül Sumru; Sever, Nihat; Genc, Nimetullah Mete; Dokucu, Ali Ihsan

2014-11-01

We aimed to compare the success rates of the double hydrodistention implantation technique (HIT) and the HIT with a polyacrylate/polyalcohol copolymer (PPC) for the treatment of primary vesicoureteral reflux (VUR) with a new nonbiodegradable tissue-augmenting substance (Vantris, Promedon, Cordoba, Argentina). Between January 2011 and December 2012, fifty-two children who underwent subureteric injection for primary VUR are included. The children were randomly separated into two groups, the HIT and the double HIT groups, according to the type of injection. Success was defined as no reflux on a follow-up voiding cystourethrogram (VCUG) after 6 months. The patients were evaluated according to sex, age, grade of reflux, number of injections, and injected volume, and the radiological success rates were compared. Fifty-two patients underwent an endoscopic injection for primary grade III-V VUR. The HIT group consisted of 26 patients with 33 ureters, and the double HIT group consisted of 26 patients with 35 ureters. There were no significant differences in terms of the sex, ages, VUR grades, bilaterality between the two groups. The mean injected volumes were ml 1.12 (1.02-1.22) in the HIT group and 1.24 ml (95 % CI 1.10-1.38) in the double HIT group. The reflux was resolved in 21/33 (63.6 %) ureters in the HIT group and in 30/35 (85.7 %) ureters in the double HIT group, (p < 0.05). We had only one complication. This patient in the double HIT group, developed bilateral hydronephrosis and oliguric renal failure requiring open reimplantation at the sixth month. We observed successful results double HIT method with PPC in Grade III-V reflux, but the long-term follow-up of patients is needed for hydronephrosis. As the double HIT treatment leads to a higher success rate, its use is preferable.

A partnership model for implementing electronic health records in resource-limited primary care settings: experiences from two nurse-managed health centers

PubMed Central

Dennehy, Patricia; White, Mary P; Hamilton, Andrew; Pohl, Joanne M; Tanner, Clare; Onifade, Tiffiani J

2011-01-01

Objective To present a partnership-based and community-oriented approach designed to ease provider anxiety and facilitate the implementation of electronic health records (EHR) in resource-limited primary care settings. Materials and Methods The approach, referred to as partnership model, was developed and iteratively refined through the research team's previous work on implementing health information technology (HIT) in over 30 safety net practices. This paper uses two case studies to illustrate how the model was applied to help two nurse-managed health centers (NMHC), a particularly vulnerable primary care setting, implement EHR and get prepared to meet the meaningful use criteria. Results The strong focus of the model on continuous quality improvement led to eventual implementation success at both sites, despite difficulties encountered during the initial stages of the project. Discussion There has been a lack of research, particularly in resource-limited primary care settings, on strategies for abating provider anxiety and preparing them to manage complex changes associated with EHR uptake. The partnership model described in this paper may provide useful insights into the work shepherded by HIT regional extension centers dedicated to supporting resource-limited communities disproportionally affected by EHR adoption barriers. Conclusion NMHC, similar to other primary care settings, are often poorly resourced, understaffed, and lack the necessary expertise to deploy EHR and integrate its use into their day-to-day practice. This study demonstrates that implementation of EHR, a prerequisite to meaningful use, can be successfully achieved in this setting, and partnership efforts extending far beyond the initial software deployment stage may be the key. PMID:21828225

Performance of machine-learning scoring functions in structure-based virtual screening

PubMed Central

Wójcikowski, Maciej; Ballester, Pedro J.; Siedlecki, Pawel

2017-01-01

Classical scoring functions have reached a plateau in their performance in virtual screening and binding affinity prediction. Recently, machine-learning scoring functions trained on protein-ligand complexes have shown great promise in small tailored studies. They have also raised controversy, specifically concerning model overfitting and applicability to novel targets. Here we provide a new ready-to-use scoring function (RF-Score-VS) trained on 15 426 active and 893 897 inactive molecules docked to a set of 102 targets. We use the full DUD-E data sets along with three docking tools, five classical and three machine-learning scoring functions for model building and performance assessment. Our results show RF-Score-VS can substantially improve virtual screening performance: RF-Score-VS top 1% provides 55.6% hit rate, whereas that of Vina only 16.2% (for smaller percent the difference is even more encouraging: RF-Score-VS top 0.1% achieves 88.6% hit rate for 27.5% using Vina). In addition, RF-Score-VS provides much better prediction of measured binding affinity than Vina (Pearson correlation of 0.56 and −0.18, respectively). Lastly, we test RF-Score-VS on an independent test set from the DEKOIS benchmark and observed comparable results. We provide full data sets to facilitate further research in this area (http://github.com/oddt/rfscorevs) as well as ready-to-use RF-Score-VS (http://github.com/oddt/rfscorevs_binary). PMID:28440302

Patients Awaiting Surgical Repair for Large Abdominal Aortic Aneurysms Can Exercise at Moderate to Hard Intensities with a Low Risk of Adverse Events

PubMed Central

Weston, Matthew; Batterham, Alan M.; Tew, Garry A.; Kothmann, Elke; Kerr, Karen; Nawaz, Shah; Yates, David; Danjoux, Gerard

2017-01-01

Purpose: Intervention fidelity refers to the extent an experimental manipulation has been implemented as intended. Our aim was to evaluate the fidelity of high-intensity interval training (HIT) in patients awaiting repair of large abdominal aortic aneurysms. Methods: Following a baseline cardiopulmonary exercise test, 27 participants performed a hospital-based, supervised HIT intervention in the 4 weeks preceding surgery. The intervention was performed thrice weekly on a cycle ergometer and involved either 8 × 2-min intervals, each interspersed by 2-min recovery periods, or 4 × 4-min intervals interspersed with 4-min recovery periods. When surgery was delayed, participants undertook one maintenance HIT session per week until surgery. Session one power output was set to baseline anaerobic threshold power output and then increased on subsequent sessions until ratings of perceived exertion (RPE; Borg CR-10) for the legs (RPE-L) and sense of breathlessness/ chest (RPE-C) were hard (5) to very hard (7) at the end of each interval. For safety, power output was maintained or reduced if systolic blood pressure exceeded 180 mm Hg or heart rate exceeded 95% of maximum. Results: Overall session attendance across the 4-week HIT intervention was 74%. Seventeen participants met our compliance criteria of ≥75% of intervention sessions and all maintenance sessions. When compared to non-compliance, compliant participants had higher fitness, performed more HIT sessions and were able to exercise at higher exercise intensities with a lower proportion of exercise safety breaches. In the 17 compliant participants, the proportion of repetitions meeting the HIT criterion was 30% (RPE-L) and 16% (RPE-C). Mean repetition intensity was 4.1 ± 2.0 Arbitrary Units [AU] (RPE-L) and 3.5 ± 1.9 AU (RPE-C) with a within-subject variability of ±1.4 AU and ±1.6 AU, respectively. We observed higher RPE scores (~0.5 AU) following 2-min intervals when compared to 4-min intervals and exercise power output increased 23% across the 4-week HIT intervention. One participant experienced an adverse event but were still able to complete their remaining exercise sessions. Conclusions: Despite an inconsistent and lower than prescribed intensity, it is possible to exercise this high-risk patient population at moderate to hard intensities with a low risk of adverse events. Clinical Trial Registration: http://www.isrctn.com/, registration number ISRCTN09433624. PMID:28119627

Multiple-Hit Parameter Estimation in Monolithic Detectors

PubMed Central

Barrett, Harrison H.; Lewellen, Tom K.; Miyaoka, Robert S.

2014-01-01

We examine a maximum-a-posteriori method for estimating the primary interaction position of gamma rays with multiple interaction sites (hits) in a monolithic detector. In assessing the performance of a multiple-hit estimator over that of a conventional one-hit estimator, we consider a few different detector and readout configurations of a 50-mm-wide square cerium-doped lutetium oxyorthosilicate block. For this study, we use simulated data from SCOUT, a Monte-Carlo tool for photon tracking and modeling scintillation- camera output. With this tool, we determine estimate bias and variance for a multiple-hit estimator and compare these with similar metrics for a one-hit maximum-likelihood estimator, which assumes full energy deposition in one hit. We also examine the effect of event filtering on these metrics; for this purpose, we use a likelihood threshold to reject signals that are not likely to have been produced under the assumed likelihood model. Depending on detector design, we observe a 1%–12% improvement of intrinsic resolution for a 1-or-2-hit estimator as compared with a 1-hit estimator. We also observe improved differentiation of photopeak events using a 1-or-2-hit estimator as compared with the 1-hit estimator; more than 6% of photopeak events that were rejected by likelihood filtering for the 1-hit estimator were accurately identified as photopeak events and positioned without loss of resolution by a 1-or-2-hit estimator; for PET, this equates to at least a 12% improvement in coincidence-detection efficiency with likelihood filtering applied. PMID:23193231

Video head impulse test: a review of the literature.

PubMed

Alhabib, Salman F; Saliba, Issam

2017-03-01

Video head impulse test (vHIT) is a new testing which able to identify the overt and covert saccades and study the gain of vestibulo-ocular reflex (VOR) of each semicircular canal. The aim of this study is to review the clinical use of vHIT in patients with vestibular disorders in different diseases. PubMed and Cochrane databases were searched for all articles that defined vHIT, compared vHIT with another clinical test, and studied the efficacy of vHIT as diagnostic tools with vestibular disease. 37 articles about vHIT were reviewed. All articles studied the vHIT in English and French languages up to May 2015 were included in the review. Editorial articles or short comments, conference abstracts, animal studies, and language restriction were excluded from the review. Four systems were used in the literature to do the vHIT. vHIT is physiological quick test, which studied the VOR at high frequency of each semicircular canal by calculating the duration ratio between the head impulse and gaze deviation. vHIT is more sensitive than clinical head impulse test (cHIT), especially in patient with isolated covert saccades. vHIT test is diagnostic of vestibular weakness by gain reduction and the appearance of overt and covert saccades. If the vHIT is normal, then caloric test is mandatory to rule out a peripheral origin of vertigo. It is recommended to test each semicircular canal, as isolated vertical canal weakness was identified in the literature. More investigation would be required to determine the evolution of the VOR gain with the progression of the vestibular disease.

Is “Hit and Run” a Single Word? The Processing of Irreversible Binomials in Neglect Dyslexia

PubMed Central

Arcara, Giorgio; Lacaita, Graziano; Mattaloni, Elisa; Passarini, Laura; Mondini, Sara; Benincà, Paola; Semenza, Carlo

2012-01-01

The present study is the first neuropsychological investigation into the problem of the mental representation and processing of irreversible binomials (IBs), i.e., word pairs linked by a conjunction (e.g., “hit and run,” “dead or alive”). In order to test their lexical status, the phenomenon of neglect dyslexia is explored. People with left-sided neglect dyslexia show a clear lexical effect: they can read IBs better (i.e., by dropping the leftmost words less frequently) when their components are presented in their correct order. This may be taken as an indication that they treat these constructions as lexical, not decomposable, elements. This finding therefore constitutes strong evidence that IBs tend to be stored in the mental lexicon as a whole and that this whole form is preferably addressed in the retrieval process. PMID:22347199

Inflammatory Mediators of Hepatic Steatosis

PubMed Central

Hijona, Elizabeth; Hijona, Lander; Arenas, Juan I.; Bujanda, Luis

2010-01-01

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming a world-wide public health problem. NAFLD represents a spectrum of disease ranging from “simple steatosis”, which is considered relatively benign, to nonalcoholic steatohepatitis and to NAFLD-associated cirrhosis and end-stage liver disease. The etiology of NAFLD and its progression is complex and remains incompletely understood. The progression of the disease involves many factors. Apart from the two hits, the accumulation of TG and the development of fibrosis and necroinflammatory processes, exit numerous molecules associated with these two hits. Among them we can highlight the pro-inflammatory molecules and adiponectins. This review focuses on the growing evidence from both experimental and human studies suggesting a central role of cytokines in the pathogenesis of NAFLD. We review the role of cytokines as key regulators of insulin sensitivity and hepatic lipid overloading, liver injury and inflammation, and fibrosis with an emphasis on potential therapeutic implications. PMID:20300479

Developing Health Information Technology (HIT) Programs and HIT Curriculum: The Southern Polytechnic State University Experience

ERIC Educational Resources Information Center

Zhang, Chi; Reichgelt, Han; Rutherfoord, Rebecca H.; Wang, Andy Ju An

2014-01-01

Health Information Technology (HIT) professionals are in increasing demand as healthcare providers need help in the adoption and meaningful use of Electronic Health Record (EHR) systems while the HIT industry needs workforce skilled in HIT and EHR development. To respond to this increasing demand, the School of Computing and Software Engineering…

Trans-ethnic follow-up of breast cancer GWAS hits using the preferential linkage disequilibrium approach

PubMed Central

Zhu, Qianqian; Shepherd, Lori; Lunetta, Kathryn L.; Yao, Song; Liu, Qian; Hu, Qiang; Haddad, Stephen A.; Sucheston-Campbell, Lara; Bensen, Jeannette T.; Bandera, Elisa V.; Rosenberg, Lynn; Liu, Song; Haiman, Christopher A.; Olshan, Andrew F.; Palmer, Julie R.; Ambrosone, Christine B.

2016-01-01

Leveraging population-distinct linkage equilibrium (LD) patterns, trans-ethnic follow-up of variants discovered from genome-wide association studies (GWAS) has proved to be useful in facilitating the identification of bona fide causal variants. We previously developed the preferential LD approach, a novel method that successfully identified causal variants driving the GWAS signals within European-descent populations even when the causal variants were only weakly linked with the GWAS-discovered variants. To evaluate the performance of our approach in a trans-ethnic setting, we applied it to follow up breast cancer GWAS hits identified mostly from populations of European ancestry in African Americans (AA). We evaluated 74 breast cancer GWAS variants in 8,315 AA women from the African American Breast Cancer Epidemiology and Risk (AMBER) consortium. Only 27% of them were associated with breast cancer risk at significance level α=0.05, suggesting race-specificity of the identified breast cancer risk loci. We followed up on those replicated GWAS hits in the AMBER consortium utilizing the preferential LD approach, to search for causal variants or better breast cancer markers from the 1000 Genomes variant catalog. Our approach identified stronger breast cancer markers for 80% of the GWAS hits with at least nominal breast cancer association, and in 81% of these cases, the marker identified was among the top 10 of all 1000 Genomes variants in the corresponding locus. The results support trans-ethnic application of the preferential LD approach in search for candidate causal variants, and may have implications for future genetic research of breast cancer in AA women. PMID:27825120

A New Socio-technical Model for Studying Health Information Technology in Complex Adaptive Healthcare Systems

PubMed Central

Sittig, Dean F.; Singh, Hardeep

2011-01-01

Conceptual models have been developed to address challenges inherent in studying health information technology (HIT). This manuscript introduces an 8-dimensional model specifically designed to address the socio-technical challenges involved in design, development, implementation, use, and evaluation of HIT within complex adaptive healthcare systems. The 8 dimensions are not independent, sequential, or hierarchical, but rather are interdependent and interrelated concepts similar to compositions of other complex adaptive systems. Hardware and software computing infrastructure refers to equipment and software used to power, support, and operate clinical applications and devices. Clinical content refers to textual or numeric data and images that constitute the “language” of clinical applications. The human computer interface includes all aspects of the computer that users can see, touch, or hear as they interact with it. People refers to everyone who interacts in some way with the system, from developer to end-user, including potential patient-users. Workflow and communication are the processes or steps involved in assuring that patient care tasks are carried out effectively. Two additional dimensions of the model are internal organizational features (e.g., policies, procedures, and culture) and external rules and regulations, both of which may facilitate or constrain many aspects of the preceding dimensions. The final dimension is measurement and monitoring, which refers to the process of measuring and evaluating both intended and unintended consequences of HIT implementation and use. We illustrate how our model has been successfully applied in real-world complex adaptive settings to understand and improve HIT applications at various stages of development and implementation. PMID:20959322

Biofragments: An Approach towards Predicting Protein Function Using Biologically Related Fragments and its Application to Mycobacterium tuberculosis CYP126

PubMed Central

Hudson, Sean A; Mashalidis, Ellene H; Bender, Andreas; McLean, Kirsty J; Munro, Andrew W; Abell, Chris

2014-01-01

We present a novel fragment-based approach that tackles some of the challenges for chemical biology of predicting protein function. The general approach, which we have termed biofragments, comprises two key stages. First, a biologically relevant fragment library (biofragment library) can be designed and constructed from known sets of substrate-like ligands for a protein class of interest. Second, the library can be screened for binding to a novel putative ligand-binding protein from the same or similar class, and the characterization of hits provides insight into the basis of ligand recognition, selectivity, and function at the substrate level. As a proof-of-concept, we applied the biofragments approach to the functionally uncharacterized Mycobacterium tuberculosis (Mtb) cytochrome P450 isoform, CYP126. This led to the development of a tailored CYP biofragment library with notable 3D characteristics and a significantly higher screening hit rate (14 %) than standard drug-like fragment libraries screened previously against Mtb CYP121 and 125 (4 % and 1 %, respectively). Biofragment hits were identified that make both substrate-like type-I and inhibitor-like type-II interactions with CYP126. A chemical-fingerprint-based substrate model was built from the hits and used to search a virtual TB metabolome, which led to the discovery that CYP126 has a strong preference for the recognition of aromatics and substrate-like type-I binding of chlorophenol moieties within the active site near the heme. Future catalytic analyses will be focused on assessing CYP126 for potential substrate oxidative dehalogenation. PMID:24677424

A new sociotechnical model for studying health information technology in complex adaptive healthcare systems.

PubMed

Sittig, Dean F; Singh, Hardeep

2010-10-01

Conceptual models have been developed to address challenges inherent in studying health information technology (HIT). This manuscript introduces an eight-dimensional model specifically designed to address the sociotechnical challenges involved in design, development, implementation, use and evaluation of HIT within complex adaptive healthcare systems. The eight dimensions are not independent, sequential or hierarchical, but rather are interdependent and inter-related concepts similar to compositions of other complex adaptive systems. Hardware and software computing infrastructure refers to equipment and software used to power, support and operate clinical applications and devices. Clinical content refers to textual or numeric data and images that constitute the 'language' of clinical applications. The human--computer interface includes all aspects of the computer that users can see, touch or hear as they interact with it. People refers to everyone who interacts in some way with the system, from developer to end user, including potential patient-users. Workflow and communication are the processes or steps involved in ensuring that patient care tasks are carried out effectively. Two additional dimensions of the model are internal organisational features (eg, policies, procedures and culture) and external rules and regulations, both of which may facilitate or constrain many aspects of the preceding dimensions. The final dimension is measurement and monitoring, which refers to the process of measuring and evaluating both intended and unintended consequences of HIT implementation and use. We illustrate how our model has been successfully applied in real-world complex adaptive settings to understand and improve HIT applications at various stages of development and implementation.

Concussion in the National Football League: viewpoint of an elite player.

PubMed

DeLamielleure, Joe

2014-01-01

Chronic traumatic encephalopathy resulting from head hits and concussions is an unfortunate illness that has affected numerous football players, especially in the National Football League. Many of my fellow players suffer from this problem, and many have died prematurely because of it. I make some suggestions for improving the situation for retired and current players. © 2014 American Society of Law, Medicine & Ethics, Inc.

NWTC Researchers Develop Wave Energy Conversion Technology | News | NREL

Science.gov Websites

capturing the energy of waves. But therein is the problem. "It's not like a wind farm where you can like buoys that move up and down in the water. The simplest type is a device that, as the waves hit engineering to control systems. "We thought to add something like a pitch control on a wind turbine."

Pull-Up Nets

ERIC Educational Resources Information Center

Meenan, Liz

2008-01-01

When the author began teaching, she always hit a problem when it came to 3D shapes. She wanted the pupils to get a feel for them, and she would get them to make the shapes from their nets. The pupils would first try to visualize how the 2D nets could become 3D shapes and then they would physically fold the nets into the shapes for themselves.…

Prototypical Content Development and Evaluation of the Cognitive English Vocabulary-Learning Program for Korean University Students

ERIC Educational Resources Information Center

Kim, Inseok

2014-01-01

Many EFL learners seem to believe that they can come to grips with the problem of vocabulary learning with a 'hit-or-miss' approach. However, a growing number of recent research reports indicate that they need to learn a repertoire of vocabulary in a systematic way for effective communication. This paper explores the development and evaluation of…

Forensic Evidence and Criminal Investigations: The Impact of Ballistics Information on the Investigation of Violent Crime in Nine Cities.

PubMed

King, William R; Campbell, Bradley A; Matusiak, Matthew C; Katz, Charles M

2017-07-01

We explore the impact of information from ballistics imaging hit reports on the investigation into violent crimes. Ballistics imaging hits link two crimes involving the same firearm by forensically matching tool marks on the fired bullets or cartridge cases. Interview data collected from detectives who received a hit report were used to explore the relationship between the presence of a hit report and outcomes in 65 gun-related violent crime investigations in nine U.S. police agencies. Findings indicate hit reports rarely contribute to identification, arrest, charging, or sentencing of suspects, because of delays in producing hit reports. On average, hit reports were completed 181.4 days after the focal crime. This delay forces investigations to proceed without the benefit of information from ballistics analysis. Additionally, hit reports rarely contained detailed information that was immediately useful to investigators. Instead, hit reports required additional research by the investigator to unlock useful information. © 2017 American Academy of Forensic Sciences.

Health information technology and physicians' perceptions of healthcare quality.

PubMed

Fang, Hai; Peifer, Karen L; Chen, Jie; Rizzo, John A

2011-03-01

To investigate the relationship between the use of health information technology (HIT) and physician perceptions of providing high-quality care and to determine whether this relationship has changed over time. We used 2 waves of longitudinal data from the Community Tracking Study Physician Surveys, 2000-2001 and 2004-2005. Three measures of HIT were examined: a binary variable measuring the use of at least 1 type of HIT, a continuous variable measuring the total number of HIT types, and a binary variable measuring use of all 5 HIT types related to "meaningful use" of HIT as defined by Centers for Medicare and Medicaid Services. Three multivariate models were estimated to study the effect of each HIT measure on physicians' perception of providing high-quality care. Individual fixed-effects estimation also was used to control for individual time-invariant factors. Using at least 1 type of HIT significantly enhanced physicians' perception of providing high-quality care in 2000-2001, but not in 2004-2005. The marginal effect of adding 1 extra HIT type was positive and statistically significant in both periods. The association between using all 5 HIT types related to meaningful use and perceived quality was statistically significant in 2000-2001, but not in 2004-2005. Health information technology has become a multifunctional system and appears to have enhanced physicians' perception of providing high-quality care. Physicians' perceptions of medical care quality improved as the number of HIT types used increased. This study supports more extensive use of HIT in physician practices.

LncRNA-HIT Functions as an Epigenetic Regulator of Chondrogenesis through Its Recruitment of p100/CBP Complexes.

PubMed

Carlson, Hanqian L; Quinn, Jeffrey J; Yang, Yul W; Thornburg, Chelsea K; Chang, Howard Y; Stadler, H Scott

2015-12-01

Gene expression profiling in E 11 mouse embryos identified high expression of the long noncoding RNA (lncRNA), LNCRNA-HIT in the undifferentiated limb mesenchyme, gut, and developing genital tubercle. In the limb mesenchyme, LncRNA-HIT was found to be retained in the nucleus, forming a complex with p100 and CBP. Analysis of the genome-wide distribution of LncRNA-HIT-p100/CBP complexes by ChIRP-seq revealed LncRNA-HIT associated peaks at multiple loci in the murine genome. Ontological analysis of the genes contacted by LncRNA-HIT-p100/CBP complexes indicate a primary role for these loci in chondrogenic differentiation. Functional analysis using siRNA-mediated reductions in LncRNA-HIT or p100 transcripts revealed a significant decrease in expression of many of the LncRNA-HIT-associated loci. LncRNA-HIT siRNA treatments also impacted the ability of the limb mesenchyme to form cartilage, reducing mesenchymal cell condensation and the formation of cartilage nodules. Mechanistically the LncRNA-HIT siRNA treatments impacted pro-chondrogenic gene expression by reducing H3K27ac or p100 activity, confirming that LncRNA-HIT is essential for chondrogenic differentiation in the limb mesenchyme. Taken together, these findings reveal a fundamental epigenetic mechanism functioning during early limb development, using LncRNA-HIT and its associated proteins to promote the expression of multiple genes whose products are necessary for the formation of cartilage.

LncRNA-HIT Functions as an Epigenetic Regulator of Chondrogenesis through Its Recruitment of p100/CBP Complexes

PubMed Central

Carlson, Hanqian L.; Quinn, Jeffrey J.; Yang, Yul W.; Thornburg, Chelsea K.; Chang, Howard Y.; Stadler, H. Scott

2015-01-01

Gene expression profiling in E 11 mouse embryos identified high expression of the long noncoding RNA (lncRNA), LNCRNA-HIT in the undifferentiated limb mesenchyme, gut, and developing genital tubercle. In the limb mesenchyme, LncRNA-HIT was found to be retained in the nucleus, forming a complex with p100 and CBP. Analysis of the genome-wide distribution of LncRNA-HIT-p100/CBP complexes by ChIRP-seq revealed LncRNA-HIT associated peaks at multiple loci in the murine genome. Ontological analysis of the genes contacted by LncRNA-HIT-p100/CBP complexes indicate a primary role for these loci in chondrogenic differentiation. Functional analysis using siRNA-mediated reductions in LncRNA-HIT or p100 transcripts revealed a significant decrease in expression of many of the LncRNA-HIT-associated loci. LncRNA-HIT siRNA treatments also impacted the ability of the limb mesenchyme to form cartilage, reducing mesenchymal cell condensation and the formation of cartilage nodules. Mechanistically the LncRNA-HIT siRNA treatments impacted pro-chondrogenic gene expression by reducing H3K27ac or p100 activity, confirming that LncRNA-HIT is essential for chondrogenic differentiation in the limb mesenchyme. Taken together, these findings reveal a fundamental epigenetic mechanism functioning during early limb development, using LncRNA-HIT and its associated proteins to promote the expression of multiple genes whose products are necessary for the formation of cartilage. PMID:26633036

Data processing pipeline for serial femtosecond crystallography at SACLA.

PubMed

Nakane, Takanori; Joti, Yasumasa; Tono, Kensuke; Yabashi, Makina; Nango, Eriko; Iwata, So; Ishitani, Ryuichiro; Nureki, Osamu

2016-06-01

A data processing pipeline for serial femtosecond crystallography at SACLA was developed, based on Cheetah [Barty et al. (2014). J. Appl. Cryst. 47 , 1118-1131] and CrystFEL [White et al. (2016). J. Appl. Cryst. 49 , 680-689]. The original programs were adapted for data acquisition through the SACLA API, thread and inter-node parallelization, and efficient image handling. The pipeline consists of two stages: The first, online stage can analyse all images in real time, with a latency of less than a few seconds, to provide feedback on hit rate and detector saturation. The second, offline stage converts hit images into HDF5 files and runs CrystFEL for indexing and integration. The size of the filtered compressed output is comparable to that of a synchrotron data set. The pipeline enables real-time feedback and rapid structure solution during beamtime.

Inflammation and the Two-Hit Hypothesis of Schizophrenia

PubMed Central

Feigenson, Keith A.; Kusnecov, Alex W.; Silverstein, Steven M.

2014-01-01

The high societal and individual cost of schizophrenia necessitates finding better, more effective treatment, diagnosis, and prevention strategies. One of the obstacles in this endeavor is the diverse set of etiologies that comprises schizophrenia. A substantial body of evidence has grown over the last few decades to suggest that schizophrenia is a heterogeneous syndrome with overlapping symptoms and etiologies. At the same time, an increasing number of clinical, epidemiological, and experimental studies have shown links between schizophrenia and inflammatory conditions. In this review, we analyze the literature on inflammation and schizophrenia, with a particular focus on comorbidity, biomarkers, and environmental insults. We then identify several mechanisms by which inflammation could influence the development of schizophrenia via the two-hit hypothesis. Lastly, we note the relevance of these findings to clinical applications in the diagnosis, prevention, and treatment of schizophrenia. PMID:24247023

Bayesian Models Leveraging Bioactivity and Cytotoxicity Information for Drug Discovery

PubMed Central

Ekins, Sean; Reynolds, Robert C.; Kim, Hiyun; Koo, Mi-Sun; Ekonomidis, Marilyn; Talaue, Meliza; Paget, Steve D.; Woolhiser, Lisa K.; Lenaerts, Anne J.; Bunin, Barry A.; Connell, Nancy; Freundlich, Joel S.

2013-01-01

SUMMARY Identification of unique leads represents a significant challenge in drug discovery. This hurdle is magnified in neglected diseases such as tuberculosis. We have leveraged public high-throughput screening (HTS) data, to experimentally validate virtual screening approach employing Bayesian models built with bioactivity information (single-event model) as well as bioactivity and cytotoxicity information (dual-event model). We virtually screen a commercial library and experimentally confirm actives with hit rates exceeding typical HTS results by 1-2 orders of magnitude. The first dual-event Bayesian model identified compounds with antitubercular whole-cell activity and low mammalian cell cytotoxicity from a published set of antimalarials. The most potent hit exhibits the in vitro activity and in vitro/in vivo safety profile of a drug lead. These Bayesian models offer significant economies in time and cost to drug discovery. PMID:23521795

Hyperinsulin therapy for calcium channel antagonist poisoning: a seven-year retrospective study.

PubMed

Espinoza, Tamara R; Bryant, Sean M; Aks, Steve E

2013-01-01

The use of hyperinsulin therapy (HIT) in severe calcium channel antagonist (CCA) poisoning has become a more common therapy within the last decade. The objective of this study is to report 7 years of experience recommending HIT. This was a retrospective chart review utilizing our regional poison center (RPC) data from January 1, 2002, through December 31, 2008. All cases of CCA poisoning receiving HIT were searched. Endpoints included the number of CCA cases utilizing HIT, insulin dose, time of initiation of HIT, patient outcome, adverse events, age, glucose concentration, and lowest systolic blood pressure recorded. Forty-six cases of CCA poisoning were managed with HIT over 7 years. All the patients received standard antidotal therapy (= intravenous fluids, calcium salts, glucagon, and pressors). HIT administration followed our RPC recommendation 23 times (50%), and no hypoglycemic events occurred. Means (age, highest glucose measured, and lowest systolic blood pressure measured) were 51 years, 282 mg/dL, and 74 mm Hg, respectively. Our RPC recommendations for HIT were followed 50% of the time over the last 7 years. In light of the lack of hypoglycemia associated with HIT in our study population, we recommend HIT as an early and safe antidote in significant CCA poisoning.

Patient safety goals for the proposed Federal Health Information Technology Safety Center.

PubMed

Sittig, Dean F; Classen, David C; Singh, Hardeep

2015-03-01

The Office of the National Coordinator for Health Information Technology is expected to oversee creation of a Health Information Technology (HIT) Safety Center. While its functions are still being defined, the center is envisioned as a public-private entity focusing on promotion of HIT related patient safety. We propose that the HIT Safety Center leverages its unique position to work with key administrative and policy stakeholders, healthcare organizations (HCOs), and HIT vendors to achieve four goals: (1) facilitate creation of a nationwide 'post-marketing' surveillance system to monitor HIT related safety events; (2) develop methods and governance structures to support investigation of major HIT related safety events; (3) create the infrastructure and methods needed to carry out random assessments of HIT related safety in complex HCOs; and (4) advocate for HIT safety with government and private entities. The convening ability of a federally supported HIT Safety Center could be critically important to our transformation to a safe and effective HIT enabled healthcare system. © The Author 2014. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of training with a dynamic moment of inertia bat on swing performance.

PubMed

Liu, Chiang; Liu, Ya-Chen; Kao, Ying-Chieh; Shiang, Tzyy-Yuang

2011-11-01

The purpose of this study was to investigate the effects of the 8-week dynamic moment of inertia (DMOI) bat training on swing velocity, batted-ball speed, hitting distance, muscle power, and grip force. The DMOI bat is characterized in that the bat could be swung more easily by reducing the moment of inertia at the initial stage of swing without decreasing the bat weight and has a faster swing velocity and lower muscle activity. Seventeen varsity baseball players were randomly assigned to the DMOI bat training group (n = 9) and the normal bat training group (n = 8). The training protocol was 7 swings each set, 5-8 sets each time, 3 times each week, and 8 weeks' training period. The results showed that the swing training with the DMOI bat for 8 weeks significantly increased swing velocity by about 6.20% (96.86 ± 8.48 vs. 102.82 ± 9.93 km·h(-1)), hitting distance by about 6.69% (80.06 ± 9.16 vs. 84.99 ± 7.26 m), muscle power of the right arm by about 12.04% (3.34 ± 0.41 vs. 3.74 ± 0.61 m), and muscle power of the left arm by about 8.23% (3.36 ± 0.46 vs. 3.61 ± 0.39 m) (p < 0.05). Furthermore, the DMOI bat training group had a significantly better change percentage in swing velocity, hitting distance, and grip force of the left hand than did the normal bat training group (p < 0.05). The findings suggested that the swing training with the DMOI bat has a positive benefit on swing performance and that the DMOI bat could be used as a new training tool in baseball.

Improving Adolescent Health Risk Assessment: A Multi-method Pilot Study.

PubMed

Thompson, Lindsay A; Wegman, Martin; Muller, Keith; Eddleton, Katie Z; Muszynski, Michael; Rathore, Mobeen; De Leon, Jessica; Shenkman, Elizabeth A

2016-12-01

Objectives Given poor compliance by providers with adolescent health risk assessment (HRA) in primary care, we describe the development and feasibility of using a health information technology (HIT)-enhanced HRA to improve the frequency of HRAs in diverse clinical settings, asking adolescents' recall of quality of care as a primary outcome. Methods We conducted focus groups and surveys with key stakeholders (Phase I) , including adolescents, clinic staff and providers to design and implement an intervention in a practice-based research network delivering private, comprehensive HRAs via tablet (Phase II). Providers and adolescents received geo-coded community resources according to individualized risks. Following the point-of-care implementation , we collected patient-reported outcomes using post-visit quality surveys (Phase III). Patient-reported outcomes from intervention and comparison clinics were analyzed using a mixed-model, fitted separately for each survey domain. Results Stakeholders agreed upon an HIT-enhanced HRA (Phase I). Twenty-two academic and community practices in north-central Florida then recruited 609 diverse adolescents (14-18 years) during primary care visits over 6 months; (mean patients enrolled = 28; median = 20; range 1-116; Phase II). Adolescents receiving the intervention later reported higher receipt of confidential/private care and counseling related to emotions and relationships (adjusted scores 0.42 vs 0.08 out of 1.0, p < .01; 0.85 vs 0.57, p < .001, respectively, Phase III) than those receiving usual care. Both are important quality indicators for adolescent well-child visits. Conclusions Stakeholder input was critical to the acceptability of the HIT-enhanced HRA. Patient recruitment data indicate that the intervention was feasible in a variety of clinical settings and the pilot evaluation data indicate that the intervention may improve adolescents' perceptions of high quality care.

The freeze on mass media campaigns in England: a natural experiment of the impact of tobacco control campaigns on quitting behaviour.

PubMed

Langley, Tessa; Szatkowski, Lisa; Lewis, Sarah; McNeill, Ann; Gilmore, Anna B; Salway, Ruth; Sims, Michelle

2014-06-01

To measure the impact of the suspension of tobacco control mass media campaigns in England in April 2010 on measures of smoking cessation behaviour. Interrupted time series design using routinely collected population-level data. Analysis of use of a range of types of smoking cessation support using segmented negative binomial regression. England. Use of non-intensive support: monthly calls to the National Health Service (NHS) quitline (April 2005-September 2011), text requests for quit support packs (December 2007-10) and web hits on the national smoking cessation website (January 2009-March 2011). Use of intensive cessation support: quarterly data on the number of people setting a quit date and 4-week quitters at the NHS Stop Smoking Services (SSS) (quarter 1, 2001 and quarter 3, 2011). During the suspension of tobacco control mass media spending, literature requests fell by 98% [95% confidence interval (CI) = 96-99], and quitline calls and web hits fell by 65% (95% CI = 43-79) and 34% (95% CI: 11-50), respectively. The number of people setting a quit date and 4-week quitters at the SSS increased throughout the study period. The suspension of tobacco control mass media campaigns in England in 2012 appeared to markedly reduce the use of smoking cessation literature, quitline calls and hits on the national smoking cessation website, but did not affect attendance at the Stop Smoking Services. Within a comprehensive tobacco control programme, mass media campaigns can play an important role in maximizing quitting activity. © 2013 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Direct oral anticoagulants for treatment of HIT: update of Hamilton experience and literature review.

PubMed

Warkentin, Theodore E; Pai, Menaka; Linkins, Lori-Ann

2017-08-31

Direct oral anticoagulants (DOACs) are attractive options for treatment of heparin-induced thrombocytopenia (HIT). We report our continuing experience in Hamilton, ON, Canada, since January 1, 2015 (when we completed our prospective study of rivaroxaban for HIT), using rivaroxaban for serologically confirmed HIT (4Ts score ≥4 points; positive platelet factor 4 [PF4]/heparin immunoassay, positive serotonin-release assay). We also performed a literature review of HIT treatment using DOACs (rivaroxaban, apixaban, dabigatran, edoxaban). We focused on patients who received DOAC therapy for acute HIT as either primary therapy (group A) or secondary therapy (group B; initial treatment using a non-DOAC/non-heparin anticoagulant with transition to a DOAC during HIT-associated thrombocytopenia). Our primary end point was occurrence of objectively documented thrombosis during DOAC therapy for acute HIT. We found that recovery without new, progressive, or recurrent thrombosis occurred in all 10 Hamilton patients with acute HIT treated with rivaroxaban. Data from the literature review plus these new data identified a thrombosis rate of 1 of 46 patients (2.2%; 95% CI, 0.4%-11.3%) in patients treated with rivaroxaban during acute HIT (group A, n = 25; group B, n = 21); major hemorrhage was seen in 0 of 46 patients. Similar outcomes in smaller numbers of patients were observed with apixaban (n = 12) and dabigatran (n = 11). DOACs offer simplified management of selected patients, as illustrated by a case of persisting (autoimmune) HIT (>2-month platelet recovery with inversely parallel waning of serum-induced heparin-independent serotonin release) with successful outpatient rivaroxaban management of HIT-associated thrombosis. Evidence supporting efficacy and safety of DOACs for acute HIT is increasing, with the most experience reported for rivaroxaban. © 2017 by The American Society of Hematology.

Evaluation of a new nanoparticle-based lateral-flow immunoassay for the exclusion of heparin-induced thrombocytopenia (HIT).

PubMed

Sachs, Ulrich J; von Hesberg, Jakob; Santoso, Sentot; Bein, Gregor; Bakchoul, Tamam

2011-12-01

Heparin-induced thrombocytopenia (HIT) is an adverse complication of heparin caused by HIT antibodies (abs) that recognise platelet factor 4-heparin (PF4/hep) complexes. Several laboratory tests are available for the confirmation and/or refutation of HIT. A reliable and rapid single-sample test is still pending. It was the objective of this study to evaluate a new lateral-flow immunoassay based on nanoparticle technology. A cohort of 452 surgical and medical patients suspected of having HIT was evaluated. All samples were tested in two IgG-specific ELISAs, in a particle gel immunoassay (PaGIA) and in a newly developed lateral-flow immunoassay (LFI-HIT) as well as in a functional test (HIPA). Clinical pre-test probability was determined using 4T's score. Platelet-activating antibodies were present in 34/452 patients, all of whom had intermediate to high clinical probability. PF4/hep abs were detected in 79, 87, 86, and 63 sera using the four different immunoassays. The negative predictive values (NPV) were 100% for both ELISA tests and LFI-HIT but only 99.2% for PaGIA. There were less false positives (n=29) in the LFI-HIT compared to any other test. Additionally, significantly less time was required to perform LFI-HIT than to perform the other immunoassays. In conclusion, a newly developed lateral-flow assay, LFI-HIT, was capable of identifying all HIT patients in a cohort in a short period of time. Beside an NPV of 100%, the rate of false-positive signals is significantly lower with LFI-HIT than with other immunoassay(s). These performance characteristics suggest a high potency in reducing the risk and costs in patients suspected of having HIT.

Elevated circulating IGF-I promotes mammary gland development and proliferation.

PubMed

Cannata, Dara; Lann, Danielle; Wu, Yingjie; Elis, Sebastien; Sun, Hui; Yakar, Shoshana; Lazzarino, Deborah A; Wood, Teresa L; Leroith, Derek

2010-12-01

Animal studies have shown that IGF-I is essential for mammary gland development. Previous studies have suggested that local IGF-I rather than circulating IGF-I is the major mediator of mammary gland development. In the present study we used the hepatic IGF-I transgenic (HIT) and IGF-I knockout/HIT (KO-HIT) mouse models to examine the effects of enhanced circulating IGF-I on mammary development in the presence and absence of local IGF-I. HIT mice express the rat IGF-I transgene under the transthyretin promoter in the liver and have elevated circulating IGF-I and normal tissue IGF-I levels. The KO-HIT mice have no tissue IGF-I and increased circulating IGF-I. Analysis of mammary gland development reveals a greater degree of complexity in HIT mice as compared to control and KO-HIT mice, which demonstrate similar degrees of mammary gland complexity. Immunohistochemical evaluation of glands of HIT mice also suggests an enhanced degree of proliferation of the mammary gland, whereas KO-HIT mice exhibit mammary gland proliferation similar to control mice. In addition, HIT mice have a higher percentage of proliferating myoepithelial and luminal cells than control mice, whereas KO-HIT mice have an equivalent percentage of proliferating myoepithelial and luminal cells as control mice. Thus, our findings show that elevated circulating IGF-I levels are sufficient to promote normal pubertal mammary epithelial development. However, HIT mice demonstrate more pronounced mammary gland development when compared to control and KO-HIT mice. This suggests that both local and endocrine IGF-I play roles in mammary gland development and that elevated circulating IGF-I accelerates mammary epithelial proliferation.

Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma.

PubMed

Aukema, Sietse M; Kreuz, Markus; Kohler, Christian W; Rosolowski, Maciej; Hasenclever, Dirk; Hummel, Michael; Küppers, Ralf; Lenze, Dido; Ott, German; Pott, Christiane; Richter, Julia; Rosenwald, Andreas; Szczepanowski, Monika; Schwaenen, Carsten; Stein, Harald; Trautmann, Heiko; Wessendorf, Swen; Trümper, Lorenz; Loeffler, Markus; Spang, Rainer; Kluin, Philip M; Klapper, Wolfram; Siebert, Reiner

2014-04-01

Chromosomal translocations affecting the MYC oncogene are the biological hallmark of Burkitt lymphomas but also occur in a subset of other mature B-cell lymphomas. If accompanied by a chromosomal break targeting the BCL2 and/or BCL6 oncogene these MYC translocation-positive (MYC(+)) lymphomas are called double-hit lymphomas, otherwise the term single-hit lymphomas is applied. In order to characterize the biological features of these MYC(+) lymphomas other than Burkitt lymphoma we explored, after exclusion of molecular Burkitt lymphoma as defined by gene expression profiling, the molecular, pathological and clinical aspects of 80 MYC-translocation-positive lymphomas (31 single-hit, 46 double-hit and 3 MYC(+)-lymphomas with unknown BCL6 status). Comparison of single-hit and double-hit lymphomas revealed no difference in MYC partner (IG/non-IG), genomic complexity, MYC expression or gene expression profile. Double-hit lymphomas more frequently showed a germinal center B-cell-like gene expression profile and had higher IGH and MYC mutation frequencies. Gene expression profiling revealed 130 differentially expressed genes between BCL6(+)/MYC(+) and BCL2(+)/MYC(+) double-hit lymphomas. BCL2(+)/MYC(+) double-hit lymphomas more frequently showed a germinal center B-like gene expression profile. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In this series of lymphomas, in which immunochemotherapy was administered in only a minority of cases, single-hit and double-hit lymphomas had a similar poor outcome in contrast to the outcome of molecular Burkitt lymphoma and lymphomas without the MYC break. Our data suggest that, after excluding molecular Burkitt lymphoma and pediatric cases, MYC(+) lymphomas are biologically quite homogeneous with single-hit and double-hit lymphomas as well as IG-MYC and non-IG-MYC(+) lymphomas sharing various molecular characteristics.

Leveraging health information technology to achieve the “triple aim” of healthcare reform

PubMed Central

Sood, Harpreet S; Bates, David W

2015-01-01

Objective To investigate experiences with leveraging health information technology (HIT) to improve patient care and population health, and reduce healthcare expenditures. Materials and methods In-depth qualitative interviews with federal government employees, health policy, HIT and medico-legal experts, health providers, physicians, purchasers, payers, patient advocates, and vendors from across the United States. Results The authors undertook 47 interviews. There was a widely shared belief that Health Information Technology for Economic and Clinical Health (HITECH) had catalyzed the creation of a digital infrastructure, which was being used in innovative ways to improve quality of care and curtail costs. There were however major concerns about the poor usability of electronic health records (EHRs), their limited ability to support multi-disciplinary care, and major difficulties with health information exchange, which undermined efforts to deliver integrated patient-centered care. Proposed strategies for enhancing the benefits of HIT included federal stimulation of competition by mandating vendors to open-up their application program interfaces, incenting development of low-cost consumer informatics tools, and promoting Congressional review of the The Health Insurance Portability and Accountability Act (HIPPA) to optimize the balance between data privacy and reuse. Many underscored the need to “kick the legs from underneath the fee-for-service model” and replace it with a data-driven reimbursement system that rewards high quality care. Conclusions The HITECH Act has stimulated unprecedented, multi-stakeholder interest in HIT. Early experiences indicate that the resulting digital infrastructure is being used to improve quality of care and curtail costs. Reform efforts are however severely limited by problems with usability, limited interoperability and the persistence of the fee-for-service paradigm—addressing these issues therefore needs to be the federal government’s main policy target. PMID:25882032

NMR screening in fragment-based drug design: a practical guide.

PubMed

Kim, Hai-Young; Wyss, Daniel F

2015-01-01

Fragment-based drug design (FBDD) comprises both fragment-based screening (FBS) to find hits and elaboration of these hits to lead compounds. Typical fragment hits have lower molecular weight (<300-350 Da) and lower initial potency but higher ligand efficiency when compared to those from high-throughput screening. NMR spectroscopy has been widely used for FBDD since it identifies and localizes the binding site of weakly interacting hits on the target protein. Here we describe ligand-based NMR methods for hit identification from fragment libraries and for functional cross-validation of primary hits.

A qualitative study of health information technology in the Canadian public health system.

PubMed

Zinszer, Kate; Tamblyn, Robyn; Bates, David W; Buckeridge, David L

2013-05-25

Although the adoption of health information technology (HIT) has advanced in Canada over the past decade, considerable challenges remain in supporting the development, broad adoption, and effective use of HIT in the public health system. Policy makers and practitioners have long recognized that improvements in HIT infrastructure are necessary to support effective and efficient public health practice. The objective of this study was to identify aspects of health information technology (HIT) policy related to public health in Canada that have succeeded, to identify remaining challenges, and to suggest future directions to improve the adoption and use of HIT in the public health system. A qualitative case study was performed with 24 key stakeholders representing national and provincial organizations responsible for establishing policy and strategic direction for health information technology. Identified benefits of HIT in public health included improved communication among jurisdictions, increased awareness of the need for interoperable systems, and improvement in data standardization. Identified barriers included a lack of national vision and leadership, insufficient investment, and poor conceptualization of the priority areas for implementing HIT in public health. The application of HIT in public health should focus on automating core processes and identifying innovative applications of HIT to advance public health outcomes. The Public Health Agency of Canada should develop the expertise to lead public health HIT policy and should establish a mechanism for coordinating public health stakeholder input on HIT policy.

Defining health information technology-related errors: new developments since to err is human.

PubMed

Sittig, Dean F; Singh, Hardeep

2011-07-25

Despite the promise of health information technology (HIT), recent literature has revealed possible safety hazards associated with its use. The Office of the National Coordinator for HIT recently sponsored an Institute of Medicine committee to synthesize evidence and experience from the field on how HIT affects patient safety. To lay the groundwork for defining, measuring, and analyzing HIT-related safety hazards, we propose that HIT-related error occurs anytime HIT is unavailable for use, malfunctions during use, is used incorrectly by someone, or when HIT interacts with another system component incorrectly, resulting in data being lost or incorrectly entered, displayed, or transmitted. These errors, or the decisions that result from them, significantly increase the risk of adverse events and patient harm. We describe how a sociotechnical approach can be used to understand the complex origins of HIT errors, which may have roots in rapidly evolving technological, professional, organizational, and policy initiatives.

Early phase drug discovery: cheminformatics and computational techniques in identifying lead series.

PubMed

Duffy, Bryan C; Zhu, Lei; Decornez, Hélène; Kitchen, Douglas B

2012-09-15

Early drug discovery processes rely on hit finding procedures followed by extensive experimental confirmation in order to select high priority hit series which then undergo further scrutiny in hit-to-lead studies. The experimental cost and the risk associated with poor selection of lead series can be greatly reduced by the use of many different computational and cheminformatic techniques to sort and prioritize compounds. We describe the steps in typical hit identification and hit-to-lead programs and then describe how cheminformatic analysis assists this process. In particular, scaffold analysis, clustering and property calculations assist in the design of high-throughput screening libraries, the early analysis of hits and then organizing compounds into series for their progression from hits to leads. Additionally, these computational tools can be used in virtual screening to design hit-finding libraries and as procedures to help with early SAR exploration. Copyright © 2012 Elsevier Ltd. All rights reserved.

Robust statistical methods for hit selection in RNA interference high-throughput screening experiments.

PubMed

Zhang, Xiaohua Douglas; Yang, Xiting Cindy; Chung, Namjin; Gates, Adam; Stec, Erica; Kunapuli, Priya; Holder, Dan J; Ferrer, Marc; Espeseth, Amy S

2006-04-01

RNA interference (RNAi) high-throughput screening (HTS) experiments carried out using large (>5000 short interfering [si]RNA) libraries generate a huge amount of data. In order to use these data to identify the most effective siRNAs tested, it is critical to adopt and develop appropriate statistical methods. To address the questions in hit selection of RNAi HTS, we proposed a quartile-based method which is robust to outliers, true hits and nonsymmetrical data. We compared it with the more traditional tests, mean +/- k standard deviation (SD) and median +/- 3 median of absolute deviation (MAD). The results suggested that the quartile-based method selected more hits than mean +/- k SD under the same preset error rate. The number of hits selected by median +/- k MAD was close to that by the quartile-based method. Further analysis suggested that the quartile-based method had the greatest power in detecting true hits, especially weak or moderate true hits. Our investigation also suggested that platewise analysis (determining effective siRNAs on a plate-by-plate basis) can adjust for systematic errors in different plates, while an experimentwise analysis, in which effective siRNAs are identified in an analysis of the entire experiment, cannot. However, experimentwise analysis may detect a cluster of true positive hits placed together in one or several plates, while platewise analysis may not. To display hit selection results, we designed a specific figure called a plate-well series plot. We thus suggest the following strategy for hit selection in RNAi HTS experiments. First, choose the quartile-based method, or median +/- k MAD, for identifying effective siRNAs. Second, perform the chosen method experimentwise on transformed/normalized data, such as percentage inhibition, to check the possibility of hit clusters. If a cluster of selected hits are observed, repeat the analysis based on untransformed data to determine whether the cluster is due to an artifact in the data. If no clusters of hits are observed, select hits by performing platewise analysis on transformed data. Third, adopt the plate-well series plot to visualize both the data and the hit selection results, as well as to check for artifacts.

Lead generation and examples opinion regarding how to follow up hits.

PubMed

Orita, Masaya; Ohno, Kazuki; Warizaya, Masaichi; Amano, Yasushi; Niimi, Tatsuya

2011-01-01

In fragment-based drug discovery (FBDD), not only identifying the starting fragment hit to be developed but also generating a drug lead from that starting fragment hit is important. Converting fragment hits to leads is generally similar to a high-throughput screening (HTS) hits-to-leads approach in that properties associated with activity for a target protein, such as selectivity against other targets and absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox), and physicochemical properties should be taken into account. However, enhancing the potency of the fragment hit is a key requirement in FBDD, unlike HTS, because initial fragment hits are generally weak. This enhancement is presently achieved by adding additional chemical groups which bind to additional parts of the target protein or by joining or combining two or more hit fragments; however, strategies for effecting greater improvements in effective activity are needed. X-ray analysis is a key technology attractive for converting fragments to drug leads. This method makes it clear whether a fragment hit can act as an anchor and provides insight regarding introduction of functional groups to improve fragment activity. Data on follow-up chemical synthesis of fragment hits has allowed for the differentiation of four different strategies: fragment optimization, fragment linking, fragment self-assembly, and fragment evolution. Here, we discuss our opinion regarding how to follow up on fragment hits, with a focus on the importance of fragment hits as an anchor moiety to so-called hot spots in the target protein using crystallographic data. Copyright © 2011 Elsevier Inc. All rights reserved.

External validation of the HIT Expert Probability (HEP) score.

PubMed

Joseph, Lee; Gomes, Marcelo P V; Al Solaiman, Firas; St John, Julie; Ozaki, Asuka; Raju, Manjunath; Dhariwal, Manoj; Kim, Esther S H

2015-03-01

The diagnosis of heparin-induced thrombocytopenia (HIT) can be challenging. The HIT Expert Probability (HEP) Score has recently been proposed to aid in the diagnosis of HIT. We sought to externally and prospectively validate the HEP score. We prospectively assessed pre-test probability of HIT for 51 consecutive patients referred to our Consultative Service for evaluation of possible HIT between August 1, 2012 and February 1, 2013. Two Vascular Medicine fellows independently applied the 4T and HEP scores for each patient. Two independent HIT expert adjudicators rendered a diagnosis of HIT likely or unlikely. The median (interquartile range) of 4T and HEP scores were 4.5 (3.0, 6.0) and 5 (3.0, 8.5), respectively. There were no significant differences between area under receiver-operating characteristic curves of 4T and HEP scores against the gold standard, confirmed HIT [defined as positive serotonin release assay and positive anti-PF4/heparin ELISA] (0.74 vs 0.73, p = 0.97). HEP score ≥ 2 was 100 % sensitive and 16 % specific for determining the presence of confirmed HIT while a 4T score > 3 was 93 % sensitive and 35 % specific. In conclusion, the HEP and 4T scores are excellent screening pre-test probability models for HIT, however, in this prospective validation study, test characteristics for the diagnosis of HIT based on confirmatory laboratory testing and expert opinion are similar. Given the complexity of the HEP scoring model compared to that of the 4T score, further validation of the HEP score is warranted prior to widespread clinical acceptance.

Recent advances in the diagnosis and treatment of heparin-induced thrombocytopenia

PubMed Central

Bakchoul, Tamam

2012-01-01

Heparin-induced thrombocytopenia (HIT) is a drug-mediated, prothrombotic disorder caused by immunization against platelet factor 4 (PF4) after complex formation with heparin or other polyanions. After their binding to PF4/heparin complexes on the platelet surface, HIT antibodies are capable of intravascular platelet activation by cross-linking Fcγ receptor IIA leading to a platelet count decrease and/or thrombosis. Diagnosis of HIT is often difficult. This, and the low specificity of the commercially available immunoassays, leads currently to substantial overdiagnosis of HIT. Timing of onset, the moderate nature of thrombocytopenia, and the common concurrence of thrombosis are very important factors, which help to differentiate HIT from other potential causes of thrombocytopenia. A combination of a clinical pretest scoring system and laboratory investigation is usually necessary to diagnose HIT. Although HIT is considered to be a rare complication of heparin treatment, the very high number of hospital inpatients, and increasingly also hospital outpatients receiving heparin, still result in a considerable number of patients developing HIT. If HIT occurs, potentially devastating complications such as life-threatening thrombosis make it one of the most serious adverse drug reactions. If HIT is strongly suspected, all heparin must be stopped and an alternative nonheparin anticoagulant started at a therapeutic dose to prevent thromboembolic complications. However, the nonheparin alternative anticoagulants bear a considerable bleeding risk, especially if given to patients with thrombocytopenia due to other reasons than HIT. While established drugs for HIT are disappearing from the market (lepirudin, danaparoid), bivalirudin, fondaparinux and potentially the new anticoagulants such as dabigatran, rivaroxaban and apixaban provide new treatment options. PMID:23606934

Is There an Association Between Heparin-Induced Thrombocytopenia (HIT) and Autoimmune Disease?

PubMed

Klinkhammer, Brent; Gruchalla, Michael

2018-03-01

Heparin-induced thrombocytopenia (HIT) is a drug-induced, immunoglobulin G medicated autoimmune disorder associated with several negative clinical outcomes including increased morbidity, mortality, and increased medical costs. Previous studies have shown associations between comorbid autoimmune diseases, but there is little known about associations between HIT and autoimmunity. To provide clinical data to suggest an association between HIT and autoimmunity. Retrospective chart review of 59 cases with a diagnosis of HIT and 251 matched controls without a HIT diagnosis, comparing the prevalence of autoimmunity in each group. A single, large upper Midwest health care system. Patients with a diagnosis of HIT were significantly more likely to have a comorbid autoimmune disease than those without a HIT diagnosis (55.9% vs 10.8%, P < 0.001). In disease-specific analyses, patients with a diagnosis of HIT were significantly more likely to have a diagnosis of antiphospholipid syndrome (15.3% vs 0.0%, P < 0.001), systemic lupus erythematous (8.5% vs 0.4%, P = 0.001), rheumatoid arthritis (5.1% vs 0.0%, P = 0.007), Hashimoto's thyroiditis (13.6% vs 3.6%, P = 0.006), or nonischemic cardiomyopathy (5.1% vs 0.0%, P = 0.007). Patients diagnosed with HIT were significantly older than controls ( P < 0.001). This novel study gives evidence to suggest an association between HIT and autoimmune disease and suggests a need for more research into the relationship between HIT and autoimmunity. These results could alter the anticoagulation management of venous thromboembolism and acute coronary syndrome in patients with a previously identified autoimmune disease. Copyright© Wisconsin Medical Society.

The effect of obesity on the rate of heparin-induced thrombocytopenia.

PubMed

Marler, Jacob L; Jones, G Morgan; Wheeler, Brian J; Alshaya, Abdulrahman; Hartmann, Jonathan L; Oliphant, Carrie S

2018-06-01

: Heparin-induced thrombocytopenia (HIT) occurs in patients receiving heparin-containing products due to the formation of platelet-activating antibodies to heparin and platelet factor 4. Diagnosis includes utilization of a scoring system known as the 4-T score, and HIT laboratory assays. Recently, obesity was identified as a potential factor associated with the development of HIT. The objective of this study was to evaluate the association of HIT with obesity in ICU and general medicine patients. We performed a chart review of adult patients within the Methodist Healthcare System, and included patients who had an ELISA and serotonin release assay laboratory tests reported within same hospital admission in which they also had documented receipt of heparin. Obese patients were compared with nonobese patients (BMI < 30) for the primary outcome of HIT occurrence, and secondary outcomes including rate of thrombosis, 4-T scores, and ELISA optical density values. We also generated a 5-T score by including one additional point for those with a BMI of 30 or more to determine the predictive value of this score in identifying HIT. Obesity was confirmed to be a risk factor for HIT, and the 5-T score model was also predictive of the development of HIT. However, the 5-T score was not statistically more predictive of HIT than the 4-T score. Predicting HIT remains challenging and novel markers of HIT are needed to improve HIT recognition. Although obesity did not improve the 4-T score, it may improve the predictability of other scoring systems, and further investigation is warranted.

Current insights into the laboratory diagnosis of HIT.

PubMed

Bakchoul, T; Zöllner, H; Greinacher, A

2014-06-01

Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction and prothrombotic disorder caused by immunization against platelet factor 4 (PF4) after complex formation with heparin or other polyanions. After antibody binding to PF4/heparin complexes, HIT antibodies are capable of intravascular platelet activation by cross-linking Fc gamma receptor IIa (FcγRIIa) on the platelet surface leading to a platelet count decrease and/or thrombosis. In contrast to most other immune-mediated disorders, the currently available laboratory tests for anti-PF4/heparin antibodies show a high sensitivity also for clinically irrelevant antibodies. This makes the diagnosis of HIT challenging and bears the risk to substantially overdiagnose HIT. The strength of the antigen assays for HIT is in ruling out HIT when the test is negative. Functional assays have a higher specificity for clinically relevant antibodies, but they are restricted to specialized laboratories. Currently, a Bayesian approach combining the clinical likelihood estimation for HIT with laboratory tests is the most appropriate approach to diagnose HIT. In this review, we give an overview on currently available diagnostic procedures and discuss their limitations. © 2014 John Wiley & Sons Ltd.

First Plasma Results from the HIT-SI Spheromak

NASA Astrophysics Data System (ADS)

Sieck, P. E.; Hamp, W. T.; Izzo, V. A.; Jarboe, T. R.; Nelson, B. A.; O'Neill, R. G.; Redd, A. J.; Smith, R. J.

2003-10-01

HIT-SI is the newest device in the Helicity Injected Torus (HIT) program. HIT-SI is a ``bow tie'' spheromak formed and sustained by Steady Inductive Helicity Injection (SIHI) current drive. SIHI injects helicity at a nearly constant rate with no open field lines intersecting the boundary. (T. R. Jarboe, Fusion Technology 36) (1), p. 85, 1999 HIT-SI has been designed with a bow tie geometry to achieve stable high-β (>10%) spheromak equilibria. (U. Shumlak and T. R. Jarboe, Phys. Plasmas 7) (7), p. 2959, 2000 Diagnostics currently include surface magnetic probes and flux loops, visible light imaging, H-alpha line radiation monitors, voltage measurements across insulating breaks, injector current Rogowski coils, and injector flux loops. HIT-SI is currently operating in parallel with experiments on HIT-II. At the conclusion of HIT-II operations, HIT-SI will inherit a multi-point Thomson Scattering system, a scanning two-chord FIR interferometer, and other advanced diagnostics, as well as more power supplies to extend the discharge duration. Results are presented which characterize injector operation and possible evidence for spheromak formation.

Ambulatory EHR functionality: a comparison of functionality lists.

PubMed

Drury, Barbara M

2006-01-01

There is a proliferation of lists intended to define and clarify the functionality of an ambulatory electronic health record system. These lists come from both private and public entities and vary in terminology, granularity, usability, and comprehensiveness. For example, functionality regarding a problem list includes the following possible definitions: * "Create and maintain patient-specific problem lists," from the HL7 Electronic Health Record Draft Standard for Trial Use. * "Provide a flexible mechanism for retrieval of encounter information that can be organized by diagnosis, problem, problem type," from the Bureau of Primary Health Care. * "The system shall associate encounters, orders, medications and notes with one or more problems," from the Certification Commission on Health Information Technology. * "Displays dates of problems on problem list," from COPIC Insurance Co. * "Shall automatically close acute problems using an automated algorithm," from the Physicians Foundations HIT Subcommittee. This article will compare the attributes of these five electronic health record functionality lists and their usefulness to different audiences-clinicians, application developers and payers.

Free Speech in a MySpace World

ERIC Educational Resources Information Center

Baule, Steven M.; Kriha, Darcy L.

2008-01-01

In the potential shadow of a "Bong Hits for Jesus" banner, complicated student speech and discipline issues arise almost daily on the Internet. Whether it is a mock MySpace page set up to make fun of a teacher or a direct threat to an assistant principal, it is often unclear exactly where school ground discipline ends and student free speech…

Managing Nonsuicidal Self-Injury in Schools: Use of a Structured Protocol to Manage the Behavior and Prevent Social Contagion

ERIC Educational Resources Information Center

Walsh, Barent; Muehlenkamp, Jennifer J.

2013-01-01

Nonsuicidal self-injury (NSSI) such as cutting, burning, self-hitting, and abrading is currently occurring at high rates in middle schools, high schools, and universities. This article focuses on understanding and managing NSSI strategically within middle and high school settings. The need for, and specific components of, a thorough staff training…

Alarms Sounded as Federal-Aid Ax Heaves into View

ERIC Educational Resources Information Center

Klein, Alyson

2012-01-01

Education advocates and the Obama administration are anxiously eyeing a series of across-the-board cuts set to hit a broad swath of federal domestic and military spending programs early next year, unless a sharply divided Congress can agree on a long-term plan to put the nation's fiscal house in order. Most education lobbyists expect such a deal…

Use of health information technology to advance evidence-based care: lessons from the VA QUERI program.

PubMed

Hynes, Denise M; Weddle, Timothy; Smith, Nina; Whittier, Erika; Atkins, David; Francis, Joseph

2010-01-01

As the Department of Veterans Affairs (VA) Health Services Research and Development Service's Quality Enhancement Research Initiative (QUERI) has progressed, health information technology (HIT) has occupied a crucial role in implementation research projects. We evaluated the role of HIT in VA QUERI implementation research, including HIT use and development, the contributions implementation research has made to HIT development, and HIT-related barriers and facilitators to implementation research. Key informants from nine disease-specific QUERI Centers. Documentation analysis of 86 implementation project abstracts followed up by semi-structured interviews with key informants from each of the nine QUERI centers. We used qualitative and descriptive analyses. We found: (1) HIT provided data and information to facilitate implementation research, (2) implementation research helped to further HIT development in a variety of uses including the development of clinical decision support systems (23 of 86 implementation research projects), and (3) common HIT barriers to implementation research existed but could be overcome by collaborations with clinical and administrative leadership. Our review of the implementation research progress in the VA revealed interdependency on an HIT infrastructure and research-based development. Collaboration with multiple stakeholders is a key factor in successful use and development of HIT in implementation research efforts and in advancing evidence-based practice.

Ranking the selectivity of PubChem screening hits by activity-based protein profiling: MMP13 as a case study.

PubMed

Nakai, Ryuichiro; Salisbury, Cleo M; Rosen, Hugh; Cravatt, Benjamin F

2009-02-01

High-throughput screening (HTS) has become an integral part of academic and industrial efforts aimed at developing new chemical probes and drugs. These screens typically generate several 'hits', or lead active compounds, that must be prioritized for follow-up medicinal chemistry studies. Among primary considerations for ranking lead compounds is selectivity for the intended target, especially among mechanistically related proteins. Here, we show how the chemical proteomic technology activity-based protein profiling (ABPP) can serve as a universal assay to rank HTS hits based on their selectivity across many members of an enzyme superfamily. As a case study, four metalloproteinase-13 (MMP13) inhibitors of similar potency originating from a publically supported HTS and reported in PubChem were tested by ABPP for selectivity against a panel of 27 diverse metalloproteases. The inhibitors could be readily separated into two groups: (1) those that were active against several metalloproteases and (2) those that showed high selectivity for MMP13. The latter set of inhibitors was thereby designated as more suitable for future medicinal chemistry optimization. We anticipate that ABPP will find general utility as a platform to rank the selectivity of lead compounds emerging from HTS assays for a wide variety of enzymes.

Upregulation of LncRNA-HIT promotes migration and invasion of non-small cell lung cancer cells by association with ZEB1.

PubMed

Jia, Xiaojing; Wang, Zhicheng; Qiu, Ling; Yang, Yanming; Wang, Yunlong; Chen, Zhishen; Liu, Zhongshan; Yu, Lei

2016-12-01

Lung cancer is the most common solid tumor and the leading cause of cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancer cases. The main reason of lung cancer-related deaths is due to tumor metastasis. But, the mechanisms of NSCLC metastasis remains poorly understood. LncRNAs play pivotal roles in multiple biological processes. LncRNA-HIT (HOXA transcript induced by TGFβ) was recently identified. LncRNA-HIT promotes cell migration, invasion, tumor growth, and metastasis. However, the detailed role of lncRNA-HIT in NSCLC remains unknown. In this study, for the first time, we revealed a novel role of lncRNA-HIT in the migration and invasion of NSCLC cells. The expression of lncRNA-HIT was significantly upregulated in NSCLC tissues and cell lines, and the expression level of lncRNA-HIT correlates with advanced disease stage and predicts unfavorable prognosis of NSCLC patients. Functional assays demonstrated that lncRNA-HIT markedly increased the ability of NSCLC cells to migrate and invade. Furthermore, the molecular mechanism by which lncRNA-HIT affects NSCLC cells was associated with regulation of ZEB1 stability. LncRNA-HIT functions as a prometastasis oncogene by directly associating with ZEB1 to regulate NSCLC. The interaction of lncRNA-HIT and ZEB1 may be a potential target for NSCLC therapy. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

When does adoption of health information technology by physician practices lead to use by physicians within the practice?

PubMed Central

McClellan, Sean R; Casalino, Lawrence P; Shortell, Stephen M; Rittenhouse, Diane R

2013-01-01

Objective We sought to determine the extent to which adoption of health information technology (HIT) by physician practices may differ from the extent of use by individual physicians, and to examine factors associated with adoption and use. Materials and methods Using cross-sectional survey data from the National Study of Small and Medium-Sized Physician Practices (July 2007–March 2009), we examined the extent to which organizational capabilities and external incentives were associated with the adoption of five key HIT functionalities by physician practices and with use of those functionalities by individual physicians. Results The rate of physician practices adopting any of the five HIT functionalities was 34.1%. When practices adopted HIT functionalities, on average, about one in seven physicians did not use those functionalities. One physician in five did not use prompts and reminders following adoption by their practice. After controlling for other factors, both adoption of HIT by practices and use of HIT by individual physicians were higher in primary care practices and larger practices. Practices reporting an emphasis on patient-centered management were not more likely than others to adopt, but their physicians were more likely to use HIT. Discussion Larger practices were most likely to have adopted HIT, but other factors, including specialty mix and self-reported patient-centered management, had a stronger influence on the use of HIT once adopted. Conclusions Adoption of HIT by practices does not mean that physicians will use the HIT. PMID:23396512

West Europe Report.

DTIC Science & Technology

1986-04-17

in the various plants the managers are becoming more active. One of the "businessmen of the year" designated by MERCADO magazine is none other than...primarily subsidies to municipalities , but the state may also withhold local tax money to force the municipalities to show restraint in their...expenditures. Doing so also hits private consumption indirectly. The problem here is that certainly many, but not all, municipalities have plenty of money. It

Spreadsheet Application Showing the Proper Elevation Angle, Points of Shot and Impact of a Projectile

ERIC Educational Resources Information Center

Benacka, Jan

2015-01-01

This paper provides the formula for the elevation angle at which a projectile has to be fired in a vacuum from a general position to hit a target at a given distance. A spreadsheet application that models the trajectory is presented, and the problem of finding the points of shot and impact of a projectile moving in a vacuum if three points of the…

FAF-Drugs3: a web server for compound property calculation and chemical library design

PubMed Central

Lagorce, David; Sperandio, Olivier; Baell, Jonathan B.; Miteva, Maria A.; Villoutreix, Bruno O.

2015-01-01

Drug attrition late in preclinical or clinical development is a serious economic problem in the field of drug discovery. These problems can be linked, in part, to the quality of the compound collections used during the hit generation stage and to the selection of compounds undergoing optimization. Here, we present FAF-Drugs3, a web server that can be used for drug discovery and chemical biology projects to help in preparing compound libraries and to assist decision-making during the hit selection/lead optimization phase. Since it was first described in 2006, FAF-Drugs has been significantly modified. The tool now applies an enhanced structure curation procedure, can filter or analyze molecules with user-defined or eight predefined physicochemical filters as well as with several simple ADMET (absorption, distribution, metabolism, excretion and toxicity) rules. In addition, compounds can be filtered using an updated list of 154 hand-curated structural alerts while Pan Assay Interference compounds (PAINS) and other, generally unwanted groups are also investigated. FAF-Drugs3 offers access to user-friendly html result pages and the possibility to download all computed data. The server requires as input an SDF file of the compounds; it is open to all users and can be accessed without registration at http://fafdrugs3.mti.univ-paris-diderot.fr. PMID:25883137

Directed Design of Experiments for Validating Probability of Detection Capability of a Testing System

NASA Technical Reports Server (NTRS)

Generazio, Edward R. (Inventor)

2012-01-01

A method of validating a probability of detection (POD) testing system using directed design of experiments (DOE) includes recording an input data set of observed hit and miss or analog data for sample components as a function of size of a flaw in the components. The method also includes processing the input data set to generate an output data set having an optimal class width, assigning a case number to the output data set, and generating validation instructions based on the assigned case number. An apparatus includes a host machine for receiving the input data set from the testing system and an algorithm for executing DOE to validate the test system. The algorithm applies DOE to the input data set to determine a data set having an optimal class width, assigns a case number to that data set, and generates validation instructions based on the case number.

Double-hit lymphomas constitute a highly aggressive subgroup in diffuse large B-cell lymphomas in the era of rituximab.

PubMed

Kobayashi, Tsutomu; Tsutsumi, Yasuhiko; Sakamoto, Natsumi; Nagoshi, Hisao; Yamamoto-Sugitani, Mio; Shimura, Yuji; Mizutani, Shinsuke; Matsumoto, Yosuke; Nishida, Kazuhiro; Horiike, Shigeo; Asano, Naoko; Nakamura, Shigeo; Kuroda, Junya; Taniwaki, Masafumi

2012-11-01

The incorporation of rituximab in immunochemotherapy has improved treatment outcomes for diffuse large B-cell lymphoma, but the prognosis for some diffuse large B-cell lymphomas remains dismal. Identification of adverse prognostic subgroups is essential for the choice of appropriate therapeutic strategy. We retrospectively investigated the impact of so-called 'double-hit' cytogenetic abnormalities, i.e. cytogenetic abnormalities involving c-MYC co-existing with other poor prognostic cytogenetic abnormalities involving BCL2, BCL6 or BACH2, on treatment outcomes for 93 consecutive diffuse large B-cell lymphoma patients. According to the revised international prognostic index, no patients were cytogenetically diagnosed with double-hit lymphomas in the 'very good' risk group or in the 'good' risk group, while 5 of 33 patients had double-hit lymphomas in the 'poor' risk group. All the double-hit lymphoma patients possessed both nodal and extranodal involvement. The overall complete response rate was 89.3%, overall survival 87.1% and progression-free survival 75.8% over 2 years (median observation period: 644 days). The complete response rates were 93.2% for the non-double-hit lymphoma patients and 40.0% for the double-hit lymphoma patients. Significantly longer progression-free survival and overall survival were observed for the 'very good' and the 'good' risk patients than for the 'poor' risk patients. Moreover, the progression-free survival of double-hit lymphoma was significantly shorter than that of the non-double-hit lymphoma 'poor' risk patients (P = 0.016). In addition, the overall survival of the double-hit lymphoma patients also tended to be shorter than that of the non-double-hit lymphoma 'poor' risk group. The diagnosis of double-hit lymphoma can help discriminate a subgroup of highly aggressive diffuse large B-cell lymphomas and indicate the need for the development of novel therapeutic strategies for double-hit lymphoma.

HIT-6 and MIDAS as measures of headache disability in a headache referral population.

PubMed

Sauro, Khara M; Rose, Marianne S; Becker, Werner J; Christie, Suzanne N; Giammarco, Rose; Mackie, Gordon F; Eloff, Arnoldas G; Gawel, Marek J

2010-03-01

The objective of this study was to compare the headache impact test (HIT-6) and the migraine disability assessment scale (MIDAS) as clinical measures of headache-related disability. The degree of headache-related disability is an important factor in treatment planning. Many quality of life and headache disability measures exist but it is unclear which of the available disability measures is the most helpful in planning and measuring headache management. We compared HIT-6 and MIDAS scores from 798 patients from the Canadian Headache Outpatient Registry and Database (CHORD). Correlation and regression analyses were used to examine the relationships between the HIT-6 and MIDAS total scores, headache frequency and intensity, and Beck Depression Inventory (BDI-II) scores. A positive correlation was found between HIT-6 and MIDAS scores (r = 0.52). The BDI-II scores correlated equally with the HIT-6 and the MIDAS (r = 0.42). There was a non-monotonic relationship between headache frequency and the MIDAS, and a non-linear monotonic relationship between headache frequency and the HIT-6 (r = 0.24). The correlation was higher between the intensity and the HIT-6 scores (r = 0.46), than MIDAS (r = 0.26) scores. Seventy-nine percent of patients fell into the most severe HIT-6 disability category, compared with the 57% of patients that fell into the most severe MIDAS disability category. Significantly more patients were placed in a more severe category with the HIT-6 than with the MIDAS (McNemar chi-square = 191 on 6 d.f., P < .0001). The HIT-6 and MIDAS appear to measure headache-related disability in a similar fashion. However, some important differences may exist. Headache intensity appears to influence HIT-6 score more than the MIDAS, whereas the MIDAS was influenced more by headache frequency. Using the HIT-6 and MIDAS together may give a more accurate assessment of a patient's headache-related disability.

78 FR 29135 - HIT Standards Committee Advisory Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting AGENCY: Office of...: HIT Standards Committee. General Function of the Committee: To provide recommendations to the National... Federal Health IT Strategic Plan, and in accordance with policies developed by the HIT Policy Committee...

76 FR 25355 - HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations AGENCY: Office of the National Coordinator for Health Information... Committee regarding health information technology standards, implementation specifications, and/or...

Post-hit dynamics of price limit hits in the Chinese stock markets

NASA Astrophysics Data System (ADS)

Wu, Ting; Wang, Yue; Li, Ming-Xia

2017-01-01

Price limit trading rules are useful to cool off traders short-term trading mania on individual stocks. The price dynamics approaching the limit boards are known as the magnet effect. However, the price dynamics after opening price limit hits are not well investigated. Here, we provide a detailed analysis on the price dynamics after the hits of up-limit or down-limit is open based on all A-share stocks traded in the Chinese stock markets. A "W" shape is found in the expected return, which reveals high probability of a continuous price limit hit on the following day. We also find that price dynamics after opening limit hits are dependent on the market trends. The time span of continuously hitting the price limit is found to an influence factor of the expected profit after the limit hit is open. Our analysis provides a better understanding of the price dynamics around the limit boards and contributes potential practical values for investors.

Organizational factors influencing health information technology adoption in long-term-care facilities.

PubMed

Wang, Tiankai; Wang, Yangmei; Moczygemba, Jackie

2014-01-01

Long-term care (LTC) is an important sector of the health care industry. However, the adoption of health information technology (HIT) systems in LTC facilities lags behind that in other sectors of health care. Previous literature has focused on the financial and technical barriers. This study examined the organizational factors associated with HIT adoption in LTC facilities. A survey of 500 LTC facilities in Texas enabled researchers to compile HIT indexes for further statistical analyses. A general linear model was used to study the associations between the clinical/administrative HIT indexes and organizational factors. The empirical outcomes show that the size of an LTC facility has a significant association with HIT adoption. Rural LTC facilities, especially freestanding ones, adopt less HIT than their urban counterparts, whereas freestanding LTC facilities have the lowest HIT adoption overall. There is not enough evidence to support ownership status as a significant factor in HIT adoption. Some implications are proposed, but further research is necessary.

Applying Human Factors Principles to Mitigate Usability Issues Related to Embedded Assumptions in Health Information Technology Design

PubMed Central

Lowry, Svetlana Z; Patterson, Emily S

2014-01-01

Background There is growing recognition that design flaws in health information technology (HIT) lead to increased cognitive work, impact workflows, and produce other undesirable user experiences that contribute to usability issues and, in some cases, patient harm. These usability issues may in turn contribute to HIT utilization disparities and patient safety concerns, particularly among “non-typical” HIT users and their health care providers. Health care disparities are associated with poor health outcomes, premature death, and increased health care costs. HIT has the potential to reduce these disparate outcomes. In the computer science field, it has long been recognized that embedded cultural assumptions can reduce the usability, usefulness, and safety of HIT systems for populations whose characteristics differ from “stereotypical” users. Among these non-typical users, inappropriate embedded design assumptions may contribute to health care disparities. It is unclear how to address potentially inappropriate embedded HIT design assumptions once detected. Objective The objective of this paper is to explain HIT universal design principles derived from the human factors engineering literature that can help to overcome potential usability and/or patient safety issues that are associated with unrecognized, embedded assumptions about cultural groups when designing HIT systems. Methods Existing best practices, guidance, and standards in software usability and accessibility were subjected to a 5-step expert review process to identify and summarize those best practices, guidance, and standards that could help identify and/or address embedded design assumptions in HIT that could negatively impact patient safety, particularly for non-majority HIT user populations. An iterative consensus-based process was then used to derive evidence-based design principles from the data to address potentially inappropriate embedded cultural assumptions. Results Design principles that may help identify and address embedded HIT design assumptions are available in the existing literature. Conclusions Evidence-based HIT design principles derived from existing human factors and informatics literature can help HIT developers identify and address embedded cultural assumptions that may underlie HIT-associated usability and patient safety concerns as well as health care disparities. PMID:27025349

Applying Human Factors Principles to Mitigate Usability Issues Related to Embedded Assumptions in Health Information Technology Design.

PubMed

Gibbons, Michael C; Lowry, Svetlana Z; Patterson, Emily S

2014-12-18

There is growing recognition that design flaws in health information technology (HIT) lead to increased cognitive work, impact workflows, and produce other undesirable user experiences that contribute to usability issues and, in some cases, patient harm. These usability issues may in turn contribute to HIT utilization disparities and patient safety concerns, particularly among "non-typical" HIT users and their health care providers. Health care disparities are associated with poor health outcomes, premature death, and increased health care costs. HIT has the potential to reduce these disparate outcomes. In the computer science field, it has long been recognized that embedded cultural assumptions can reduce the usability, usefulness, and safety of HIT systems for populations whose characteristics differ from "stereotypical" users. Among these non-typical users, inappropriate embedded design assumptions may contribute to health care disparities. It is unclear how to address potentially inappropriate embedded HIT design assumptions once detected. The objective of this paper is to explain HIT universal design principles derived from the human factors engineering literature that can help to overcome potential usability and/or patient safety issues that are associated with unrecognized, embedded assumptions about cultural groups when designing HIT systems. Existing best practices, guidance, and standards in software usability and accessibility were subjected to a 5-step expert review process to identify and summarize those best practices, guidance, and standards that could help identify and/or address embedded design assumptions in HIT that could negatively impact patient safety, particularly for non-majority HIT user populations. An iterative consensus-based process was then used to derive evidence-based design principles from the data to address potentially inappropriate embedded cultural assumptions. Design principles that may help identify and address embedded HIT design assumptions are available in the existing literature. Evidence-based HIT design principles derived from existing human factors and informatics literature can help HIT developers identify and address embedded cultural assumptions that may underlie HIT-associated usability and patient safety concerns as well as health care disparities.

PF4/heparin-antibody complex induces monocyte tissue factor expression and release of tissue factor positive microparticles by activation of FcγRI

PubMed Central

Glover, Sam L.; Jonas, William; McEachron, Troy; Pawlinski, Rafal; Arepally, Gowthami M.; Key, Nigel S.; Mackman, Nigel

2012-01-01

Heparin-induced thrombocytopenia (HIT) is a potentially devastating form of drug-induced thrombocytopenia that occurs in patients receiving heparin for prevention or treatment of thrombosis. Patients with HIT develop autoantibodies to the platelet factor 4 (PF4)/heparin complex, which is termed the HIT Ab complex. Despite a decrease in the platelet count, the most feared complication of HIT is thrombosis. The mechanism of thrombosis in HIT remains poorly understood. We investigated the effects of the HIT Ab complex on tissue factor (TF) expression and release of TF-positive microparticles in peripheral blood mononuclear cells and monocytes. To model these effects ex vivo, we used a murine mAb specific for the PF4/heparin complex (KKO), as well as plasma from patients with HIT. We found that the HIT Ab complex induced TF expression in monocytes and the release of TF-positive microparticles. Further, we found that induction of TF is mediated via engagement of the FcγRI receptor and activation of the MEK1-ERK1/2 signaling pathway. Our data suggest that monocyte TF may contribute to the development of thrombosis in patients with HIT. PMID:22394597

Utilizing Health Information Technology to Support Universal Healthcare Delivery: Experience of a National Healthcare System.

PubMed

Syed-Abdul, Shabbir; Hsu, Min-Huei; Iqbal, Usman; Scholl, Jeremiah; Huang, Chih-Wei; Nguyen, Phung Anh; Lee, Peisan; García-Romero, Maria Teresa; Li, Yu-Chuan Jack; Jian, Wen-Shan

2015-09-01

Recent discussions have focused on using health information technology (HIT) to support goals related to universal healthcare delivery. These discussions have generally not reflected on the experience of countries with a large amount of experience using HIT to support universal healthcare on a national level. HIT was compared globally by using data from the Ministry of the Interior, Republic of China (Taiwan). Taiwan has been providing universal healthcare since 1995 and began to strategically implement HIT on a national level at that time. Today the national-level HIT system is more extensive in Taiwan than in many other countries and is used to aid administration, clinical care, and public health. The experience of Taiwan thus can provide an illustration of how HIT can be used to support universal healthcare delivery. In this article we present an overview of some key historical developments and successes in the adoption of HIT in Taiwan over a 17-year period, as well as some more recent developments. We use this experience to offer some strategic perspectives on how it can aid in the adoption of large-scale HIT systems and on how HIT can be used to support universal healthcare delivery.

Novel 2-Phenoxyanilide Congeners Derived from a Hit Structure of the TCAMS: Synthesis and Evaluation of Their in Vitro Activity against Plasmodium falciparum.

PubMed

Weidner, Thomas; Nasereddin, Abed; Preu, Lutz; Grünefeld, Johann; Dzikowski, Ron; Kunick, Conrad

2016-02-17

The Tres Cantos Antimalarial Compound Set (TCAMS) is a publicly available compound library which contains 13533 hit structures with confirmed activity against Plasmodium falciparum, the infective agent responsible for malaria tropica. The TCAMS provides a variety of starting points for the investigation of new antiplasmodial drug leads. One of the promising compounds is TCMDC-137332, which seemed to be a good starting point due to its antiplasmodial potency and its predicted physicochemical properties. Several new analogues based on a 2-phenoxyanilide scaffold were synthesized by standard amide coupling reactions and were fully characterized regarding their identity and purity by spectroscopic and chromatographic methods. Furthermore, the results of the biological evaluation of all congeners against Plasmodium falciparum NF54 strains are presented. The findings of our in vitro screening could not confirm the presumed nanomolar antiplasmodial activity of TCMDC-137332 and its derivatives.

Footprinting of Inhibitor Interactions of In Silico Identified Inhibitors of Trypanothione Reductase of Leishmania Parasite

PubMed Central

Venkatesan, Santhosh K.; Dubey, Vikash Kumar

2012-01-01

Structure-based virtual screening of NCI Diversity set II compounds was performed to indentify novel inhibitor scaffolds of trypanothione reductase (TR) from Leishmania infantum. The top 50 ranked hits were clustered using the AuPoSOM tool. Majority of the top-ranked compounds were Tricyclic. Clustering of hits yielded four major clusters each comprising varying number of subclusters differing in their mode of binding and orientation in the active site. Moreover, for the first time, we report selected alkaloids and dibenzothiazepines as inhibitors of Leishmania infantum TR. The mode of binding observed among the clusters also potentiates the probable in vitro inhibition kinetics and aids in defining key interaction which might contribute to the inhibition of enzymatic reduction of T[S] 2. The method provides scope for automation and integration into the virtual screening process employing docking softwares, for clustering the small molecule inhibitors based upon protein-ligand interactions. PMID:22550471

Open Source Drug Discovery: Highly Potent Antimalarial Compounds Derived from the Tres Cantos Arylpyrroles

PubMed Central

2016-01-01

The development of new antimalarial compounds remains a pivotal part of the strategy for malaria elimination. Recent large-scale phenotypic screens have provided a wealth of potential starting points for hit-to-lead campaigns. One such public set is explored, employing an open source research mechanism in which all data and ideas were shared in real time, anyone was able to participate, and patents were not sought. One chemical subseries was found to exhibit oral activity but contained a labile ester that could not be replaced without loss of activity, and the original hit exhibited remarkable sensitivity to minor structural change. A second subseries displayed high potency, including activity within gametocyte and liver stage assays, but at the cost of low solubility. As an open source research project, unexplored avenues are clearly identified and may be explored further by the community; new findings may be cumulatively added to the present work. PMID:27800551

Synthesis and evaluation of a series of 6-chloro-4-methylumbelliferyl glycosides as fluorogenic reagents for screening metagenomic libraries for glycosidase activity.

PubMed

Chen, Hong-Ming; Armstrong, Zachary; Hallam, Steven J; Withers, Stephen G

2016-02-08

Screening of large enzyme libraries such as those derived from metagenomic sources requires sensitive substrates. Fluorogenic glycosides typically offer the best sensitivity but typically must be used in a stopped format to generate good signal. Use of fluorescent phenols of pKa < 7, such as halogenated coumarins, allows direct screening at neutral pH. The synthesis and characterisation of a set of nine different glycosides of 6-chloro-4-methylumbelliferone are described. The use of these substrates in a pooled format for screening of expressed metagenomic libraries yielded a "hit rate" of 1 in 60. Hits were then readily deconvoluted with the individual substrates in a single plate to identify specific activities within each clone. The use of such a collection of substrates greatly accelerates the screening process. Copyright © 2015 Elsevier Ltd. All rights reserved.

A study of the feasibility of Internet administration of a computerized health survey: the headache impact test (HIT).

PubMed

Bayliss, M S; Dewey, J E; Dunlap, I; Batenhorst, A S; Cady, R; Diamond, M L; Sheftell, F

2003-12-01

Headache impact test (HIT) is a precise, practical tool that quantifies the impact of headache on respondents' lives. It is the first widely-available dynamic health assessment (DynHA). Applications of this brief, precise survey include population based screening for disabling headaches, tracking of individual patient scores over time, disease management programs and others. We use data from Internet HIT assessments during the fall of 2000 to (1) evaluate characteristics of respondents and assessments, (2) assess the utility of joint administration of HIT and the SF-8 Health Survey (SF-8) to screen for migraine and depression, and (3) explore associations between HIT scores and subsequent healthcare-related attitudes and behaviors. We analyzed Internet HIT surveys completed between 9/1 and 11/30/2000 (n = 19,195). Subsamples include respondents who also completed (1) a 12-item Internet survey assessing severity, frequency, cause and management of headaches; (2) an e-mail survey measuring healthcare-related behaviors; (3) the SF-8; or (4) the website registration process, providing age and gender data. We used analysis of variance (ANOVA) to evaluate HIT score differences associated with age, gender, headache severity or frequency, and healthcare-related behaviors and attitudes and chi2 tests to assess the prevalence and comorbidity of migraine and depression. Three-quarters of respondents achieved a precise HIT score in < or = 5 items. Most had moderate/severe headaches; 65% had headaches at least monthly. HIT scores were directly related to headache severity and frequency. Most respondents were females, with significantly higher HIT scores than males. Most HIT respondents were between ages 25 and 54 (HIT scores were higher for younger respondents). Sixty four percent screened positive for migraine; 20% for depression. Both conditions were more prevalent among females than males. Comorbid migraine and depression was 50% more prevalent among females and increased with age until age 50. Patients with worse headache impact were more likely to seek care, discuss headaches with their providers and find HIT useful. It is feasible to use Internet-based dynamic assessments to measure health status. These data complement previous results showing that HIT differentiates respondents according to headache characteristics (severity and frequency). HIT plus SF-8 yields a practical screen for migraine and depression in headache patients and may lead to more effective treatment for patients with these conditions. Preliminary findings suggest that the experience of taking HIT on the Internet may motivate headache patients to seek care and discuss headaches with their providers.

Approved Methods and Algorithms for DoD Risk-Based Explosives Siting

DTIC Science & Technology

2007-02-02

glass. Pgha Probability of a person being in the glass hazard area Phit Probability of hit Phit (f) Probability of hit for fatality Phit (maji...Probability of hit for major injury Phit (mini) Probability of hit for minor injury Pi Debris probability densities at the ES PMaj (pair) Individual...combined high-angle and combined low-angle tables. A unique probability of hit is calculated for the three consequences of fatality, Phit (f), major injury

Validation of single-fluid and two-fluid magnetohydrodynamic models of the helicity injected torus spheromak experiment with the NIMROD code

NASA Astrophysics Data System (ADS)

Akcay, Cihan; Kim, Charlson C.; Victor, Brian S.; Jarboe, Thomas R.

2013-08-01

We present a comparison study of 3-D pressureless resistive MHD (rMHD) and 3-D presureless two-fluid MHD models of the Helicity Injected Torus with Steady Inductive helicity injection (HIT-SI). HIT-SI is a current drive experiment that uses two geometrically asymmetric helicity injectors to generate and sustain toroidal plasmas. The comparable size of the collisionless ion skin depth di to the resistive skin depth predicates the importance of the Hall term for HIT-SI. The simulations are run with NIMROD, an initial-value, 3-D extended MHD code. The modeled plasma density and temperature are assumed uniform and constant. The helicity injectors are modeled as oscillating normal magnetic and parallel electric field boundary conditions. The simulations use parameters that closely match those of the experiment. The simulation output is compared to the formation time, plasma current, and internal and surface magnetic fields. Results of the study indicate 2fl-MHD shows quantitative agreement with the experiment while rMHD only captures the qualitative features. The validity of each model is assessed based on how accurately it reproduces the global quantities as well as the temporal and spatial dependence of the measured magnetic fields. 2fl-MHD produces the current amplification Itor/Iinj and formation time τf demonstrated by HIT-SI with similar internal magnetic fields. rMHD underestimates Itor/Iinj and exhibits much a longer τf. Biorthogonal decomposition (BD), a powerful mathematical tool for reducing large data sets, is employed to quantify how well the simulations reproduce the measured surface magnetic fields without resorting to a probe-by-probe comparison. BD shows that 2fl-MHD captures the dominant surface magnetic structures and the temporal behavior of these features better than rMHD.

Cutaneous double-hit B-cell lymphoma: an aggressive form of B-cell lymphoma with a propensity for cutaneous dissemination.

PubMed

Magro, Cynthia M; Wang, Xuan; Subramaniyam, Shivakumar; Darras, Natasha; Mathew, Susan

2014-04-01

Diffuse large cell B-cell lymphoma of the skin is most commonly represented by diffuse large cell variants of primary cutaneous follicle center cell lymphoma and the leg-type lymphoma. In a minority of cases, the infiltrates are an expression of stage 4 disease of established extracutaneous B-cell lymphoma. We describe 3 patients with an aggressive form of B-cell lymphoma secondarily involving the skin. Two of the patients were in the ninth decade of life, whereas 1 patient was 34 years of age. In the elderly patients, there was an antecedent and/or concurrent history of follicular lymphoma, whereas in the younger patient, the tumor was a de novo presentation of this aggressive form of lymphoma. The elderly patients succumbed to their disease within less than a year from the time of diagnosis, whereas 1 patient is alive but with persistent and progressive disease despite chemotherapeutic intervention. The infiltrates in all 3 cases were diffuse and composed of large malignant hematopoietic cells that exhibited a round nucleus with a finely dispersed chromatin. Phenotypically, the tumor cells were Bcl-2 and CD10 positive, whereas Bcl-6 and Mum-1 showed variable positivity. One case showed combined Mum-1 positivity along with an acute lymphoblastic lymphoma phenotype, including the absence of CD20 expression. In each case, there was a c-MYC and BCL2/IGH rearrangement diagnostic of double-hit lymphoma. In one case, there was an additional BCL6 rearrangement, defining what is in essence triple-hit lymphoma. In conclusion, double-hit lymphoma is an aggressive form of B-cell neoplasia resistant to standard chemotherapy regimens, which in many but not all cases represents tumor progression in the setting of a lower grade B-cell malignancy.

Registration of central paths and colonic polyps between supine and prone scans in computed tomography colonography: Pilot study

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

Li Ping; Napel, Sandy; Acar, Burak

2004-10-01

Computed tomography colonography (CTC) is a minimally invasive method that allows the evaluation of the colon wall from CT sections of the abdomen/pelvis. The primary goal of CTC is to detect colonic polyps, precursors to colorectal cancer. Because imperfect cleansing and distension can cause portions of the colon wall to be collapsed, covered with water, and/or covered with retained stool, patients are scanned in both prone and supine positions. We believe that both reading efficiency and computer aided detection (CAD) of CTC images can be improved by accurate registration of data from the supine and prone positions. We developed amore » two-stage approach that first registers the colonic central paths using a heuristic and automated algorithm and then matches polyps or polyp candidates (CAD hits) by a statistical approach. We evaluated the registration algorithm on 24 patient cases. After path registration, the mean misalignment distance between prone and supine identical anatomic landmarks was reduced from 47.08 to 12.66 mm, a 73% improvement. The polyp registration algorithm was specifically evaluated using eight patient cases for which radiologists identified polyps separately for both supine and prone data sets, and then manually registered corresponding pairs. The algorithm correctly matched 78% of these pairs without user input. The algorithm was also applied to the 30 highest-scoring CAD hits in the prone and supine scans and showed a success rate of 50% in automatically registering corresponding polyp pairs. Finally, we computed the average number of CAD hits that need to be manually compared in order to find the correct matches among the top 30 CAD hits. With polyp registration, the average number of comparisons was 1.78 per polyp, as opposed to 4.28 comparisons without polyp registration.« less

Development and experimental test of support vector machines virtual screening method for searching Src inhibitors from large compound libraries.

PubMed

Han, Bucong; Ma, Xiaohua; Zhao, Ruiying; Zhang, Jingxian; Wei, Xiaona; Liu, Xianghui; Liu, Xin; Zhang, Cunlong; Tan, Chunyan; Jiang, Yuyang; Chen, Yuzong

2012-11-23

Src plays various roles in tumour progression, invasion, metastasis, angiogenesis and survival. It is one of the multiple targets of multi-target kinase inhibitors in clinical uses and trials for the treatment of leukemia and other cancers. These successes and appearances of drug resistance in some patients have raised significant interest and efforts in discovering new Src inhibitors. Various in-silico methods have been used in some of these efforts. It is desirable to explore additional in-silico methods, particularly those capable of searching large compound libraries at high yields and reduced false-hit rates. We evaluated support vector machines (SVM) as virtual screening tools for searching Src inhibitors from large compound libraries. SVM trained and tested by 1,703 inhibitors and 63,318 putative non-inhibitors correctly identified 93.53%~ 95.01% inhibitors and 99.81%~ 99.90% non-inhibitors in 5-fold cross validation studies. SVM trained by 1,703 inhibitors reported before 2011 and 63,318 putative non-inhibitors correctly identified 70.45% of the 44 inhibitors reported since 2011, and predicted as inhibitors 44,843 (0.33%) of 13.56M PubChem, 1,496 (0.89%) of 168 K MDDR, and 719 (7.73%) of 9,305 MDDR compounds similar to the known inhibitors. SVM showed comparable yield and reduced false hit rates in searching large compound libraries compared to the similarity-based and other machine-learning VS methods developed from the same set of training compounds and molecular descriptors. We tested three virtual hits of the same novel scaffold from in-house chemical libraries not reported as Src inhibitor, one of which showed moderate activity. SVM may be potentially explored for searching Src inhibitors from large compound libraries at low false-hit rates.

The effect of training on the use of tobacco-use cessation guidelines in dental settings

PubMed Central

Walsh, Margaret M.; Belek, Marilyn; Prakash, Preeti; Grimes, Barbara; Heckman, Barbara; Kaufman, Nathan; Meckstroth, Richard; Kavanagh, Ms. Catherine; Murray, Jana; Weintraub, Jane A.; Silverstein, Steven; Gansky, Stuart A.

2014-01-01

Background An increase in the number of dentists conducting tobacco-use cessation treatment is needed. The authors assessed the effects of high-intensity training (HIT) or low-intensity training (LIT) and reimbursement on general dentists’ tobacco-use–related attitudes and treatment behaviors. Methods The authors randomly selected 265 dentists in three states and assigned them to one of five groups: HIT workshop groups with and without tobacco-use cessation counseling reimbursement, LIT mailed self-study groups with and without reimbursement or a control group. Outcomes at follow-up were dentists’ self-reported tobacco-use–related attitudes and behaviors and patients’ reports of dentists’ behaviors. Results Significantly more dentists in the intervention groups reported having positive attitudes and behaviors at follow-up than did dentists in the control group. Dentists in the HIT groups, however, reported assessing patients’ willingness to quit and assisting them with the quitting process significantly more often than did dentists in the LIT groups. Significantly more patients of dentists in the intervention groups who used tobacco reported receiving advice and assistance from their dentists than did patients of dentists in the control group. Adding reimbursement to HIT or LIT conditions did not provide additional intervention effect. Conclusion Dentists trained by means of a workshop or self-study program used components of a recommended guideline more frequently and felt more positive toward tobacco-use cessation counseling than did dentists in the control group. Clinical Implications Although the workshop training was more successful than the self-study training, the latter’s reach among dentists could have a more significant public health impact. The effect of reimbursement needs further study. PMID:22653940

Emerging Issues and Opportunities in Health Information Technology.

PubMed

Nardi, Elizabeth A; Lentz, Lisa Korin; Winckworth-Prejsnar, Katherine; Abernethy, Amy P; Carlson, Robert W

2016-10-01

When used effectively, health information technology (HIT) can transform clinical care and contribute to new research discoveries. Despite advances in HIT and increased electronic health record adoption, many challenges to optimal use, interoperability, and data sharing exist. Data standardization across systems is limited, and scanned medical note documents result in unstructured data that make reporting on quality measures for reimbursement burdensome. Different policies and initiatives, including the Health Information Technology for Economic and Clinical Health Act, the Medicare Access and CHIP Reauthorization Act, and the National Cancer Moonshot initiative, among others, all recognize the impact that HIT can have on cancer care. Given the growing role HIT plays in health care, it is vital to have effective and efficient HIT systems that can exchange information, collect credible data that is analyzable at the point of care, and improves the patient-provider relationship. In June 2016, NCCN hosted the Emerging Issues and Opportunities in Health Information Technology Policy Summit. The summit addressed challenges, issues, and opportunities in HIT as they relate to cancer care. Keynote presentations and panelists discussed moving beyond Meaningful Use, HIT readiness to support and report on quality care, the role of HIT in precision medicine, the role of HIT in the National Cancer Moonshot initiative, and leveraging HIT to improve quality of clinical care. Copyright © 2016 by the National Comprehensive Cancer Network.

Comparison of Health Information Technology Use Between American Adults With and Without Chronic Health Conditions: Findings From The National Health Interview Survey 2012

PubMed Central

Lauche, Romy; Sibbritt, David; Olaniran, Bolanle; Cook, Ronald; Adams, Jon

2017-01-01

Background Health information technology (HIT) is utilized by people with different chronic conditions such as diabetes and hypertension. However, there has been no comparison of HIT use between persons without a chronic condition, with one chronic condition, and multiple (≥2) chronic conditions (MCCs). Objective The aim of the study was to assess the difference in HIT use between persons without a chronic condition, with one chronic condition, and with MCCs, to describe the characteristics of HIT use among those with chronic conditions and to identify the predictors of HIT use of the persons with one chronic condition and MCCs. Methods A secondary data analysis was conducted in spring 2017 using the National Health Interview Survey (NHIS) 2012 Family Core and Sample Adult Core datasets that yielded 34,525 respondents aged 18 years and older. Measures included overall HIT use (ie, any use of the following five HIT on the Internet: seeking health information, ordering prescription, making appointment, emailing health provider, and using health chat groups), as well as sociodemographic and health-related characteristics. Sociodemographic and health characteristics were compared between HIT users and nonusers among those who reported having at least one chronic condition using chi-square tests. Independent predictors of HIT use were identified using multiple logistic regression analyses for those with one chronic condition, with MCCs, and without a chronic condition. Analyses were weighted and performed at significance level of .005. Results In 2012, adults with one health chronic condition (raw count 4147/8551, weighted percentage 48.54%) was significantly higher than among those with MCCs (3816/9637, 39.55%) and those with none of chronic condition (7254/16,337, 44.40%, P<.001). Seeking health information was the most prevalent HIT use. Chi-square tests revealed that among adults with chronic conditions, those who used HIT were significantly different from their counterpart peers who did not use HIT in terms of sociodemographic and health characteristics (P<.001). Overall, the significant factors related to HIT use were similar among the adults with one chronic condition, with MCCs, or without a chronic condition: younger age, female sex, non-Hispanic white, higher education level, and higher income level were shown to be positively related to the HIT use. Conclusions This study provides a snapshot of HIT use among those with chronic conditions and potential factors related to such use. Clinical care and public health communication efforts attempting to leverage more HIT use should acknowledge differential HIT usage as identified in this study to better address communication inequalities and persistent disparities in socioeconomic status. PMID:28982644

Comparison of Health Information Technology Use Between American Adults With and Without Chronic Health Conditions: Findings From The National Health Interview Survey 2012.

PubMed

Zhang, Yan; Lauche, Romy; Sibbritt, David; Olaniran, Bolanle; Cook, Ronald; Adams, Jon

2017-10-05

Health information technology (HIT) is utilized by people with different chronic conditions such as diabetes and hypertension. However, there has been no comparison of HIT use between persons without a chronic condition, with one chronic condition, and multiple (≥2) chronic conditions (MCCs). The aim of the study was to assess the difference in HIT use between persons without a chronic condition, with one chronic condition, and with MCCs, to describe the characteristics of HIT use among those with chronic conditions and to identify the predictors of HIT use of the persons with one chronic condition and MCCs. A secondary data analysis was conducted in spring 2017 using the National Health Interview Survey (NHIS) 2012 Family Core and Sample Adult Core datasets that yielded 34,525 respondents aged 18 years and older. Measures included overall HIT use (ie, any use of the following five HIT on the Internet: seeking health information, ordering prescription, making appointment, emailing health provider, and using health chat groups), as well as sociodemographic and health-related characteristics. Sociodemographic and health characteristics were compared between HIT users and nonusers among those who reported having at least one chronic condition using chi-square tests. Independent predictors of HIT use were identified using multiple logistic regression analyses for those with one chronic condition, with MCCs, and without a chronic condition. Analyses were weighted and performed at significance level of .005. In 2012, adults with one health chronic condition (raw count 4147/8551, weighted percentage 48.54%) was significantly higher than among those with MCCs (3816/9637, 39.55%) and those with none of chronic condition (7254/16,337, 44.40%, P<.001). Seeking health information was the most prevalent HIT use. Chi-square tests revealed that among adults with chronic conditions, those who used HIT were significantly different from their counterpart peers who did not use HIT in terms of sociodemographic and health characteristics (P<.001). Overall, the significant factors related to HIT use were similar among the adults with one chronic condition, with MCCs, or without a chronic condition: younger age, female sex, non-Hispanic white, higher education level, and higher income level were shown to be positively related to the HIT use. This study provides a snapshot of HIT use among those with chronic conditions and potential factors related to such use. Clinical care and public health communication efforts attempting to leverage more HIT use should acknowledge differential HIT usage as identified in this study to better address communication inequalities and persistent disparities in socioeconomic status. ©Yan Zhang, Romy Lauche, David Sibbritt, Bolanle Olaniran, Ronald Cook, Jon Adams. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 05.10.2017.

Effects of vascular flow and PEEP in a multiple hit model of lung injury in isolated perfused rabbit lungs.

PubMed

Piacentini, Enrique; López-Aguilar, Josefina; García-Martín, Carolina; Villagrá, Ana; Saenz-Valiente, Alicia; Murias, Gastón; Fernández-Segoviano, Pilar; Hotchkiss, John R; Blanch, Lluis

2008-07-01

High vascular flow aggravates lung damage in animal models of ventilator-induced lung injury. Positive end-expiratory pressure (PEEP) can attenuate ventilator-induced lung injury, but its continued effectiveness in the setting of antecedent lung injury is unclear. The objective of the present study was to evaluate whether the application of PEEP diminishes lung injury induced by concurrent high vascular flow and high alveolar pressures in normal lungs and in a preinjury lung model. Two series of experiments were performed. Fifteen sets of isolated rabbit lungs were randomized into three groups (n = 5): low vascular flow/low PEEP; high vascular flow/low PEEP, and high vascular flow/high PEEP. Subsequently, the same protocol was applied in an additional 15 sets of isolated rabbit lungs in which oleic acid was added to the vascular perfusate to produce mild to moderate lung injury. All lungs were ventilated with peak airway pressure of 30 cm H2O for 30 minutes. Outcome measures included frequency of gross structural failure, pulmonary hemorrhage, edema formation, changes in static compliance, pulmonary vascular resistance, and pulmonary ultrafiltration coefficient. In the context of high vascular flow, application of a moderate level of PEEP reduced pulmonary rupture, edema formation, and lung hemorrhage. The protective effects of PEEP were not observed in lungs concurrently injured with oleic acid. Under these experimental conditions, PEEP attenuates lung injury in the setting of high vascular flow. The protective effect of PEEP is lost in a two-hit model of lung injury.

Evaluation of flow cytometric HIT assays in relation to an IgG-Specific immunoassay and clinical outcome.

PubMed

Kerényi, Adrienne; Beke Debreceni, Ildikó; Oláh, Zsolt; Ilonczai, Péter; Bereczky, Zsuzsanna; Nagy, Béla; Muszbek, László; Kappelmayer, János

2017-09-01

Heparin-induced thrombocytopenia (HIT) is a severe side effect of heparin treatment caused by platelet activating IgG antibodies generated against the platelet factor 4 (PF4)-heparin complex. Thrombocytopenia and thrombosis are the leading clinical symptoms of HIT. The clinical pretest probability of HIT was evaluated by the 4T score system. Laboratory testing of HIT was performed by immunological detection of antibodies against PF4-heparin complex (EIA) and two functional assays. Heparin-dependent activation of donor platelets by patient plasma was detected by flow cytometry. Increased binding of Annexin-V to platelets and elevated number of platelet-derived microparticles (PMP) were the indicators of platelet activation. EIA for IgG isotype HIT antibodies was performed in 405 suspected HIT patients. Based on negative EIA results, HIT was excluded in 365 (90%) of cases. In 40 patients with positive EIA test result functional tests were performed. Platelet activating antibodies were detected in 17 cases by Annexin V binding. PMP count analysis provided nearly identical results. The probability of a positive flow cytometric assay result was higher in patients with elevated antibody titer. 71% of patients with positive EIA and functional assay had thrombosis. EIA is an important first line laboratory test in the diagnosis of HIT; however, HIT must be confirmed by a functional test. Annexin V binding and PMP assays using flow cytometry are functional HIT tests convenient in a clinical diagnostic laboratory. The positive results of functional assays may predict the onset of thrombosis. © 2016 International Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

Creating a safe place for pediatric care: A no hit zone.

PubMed

Frazier, Erin R; Liu, Gilbert C; Dauk, Kelly L

2014-07-01

Our goal was to create and implement a program, Kosair Children's Hospital's No Hit Zone, which trains health care workers in de-escalation techniques to address parental disruptive behaviors and physical discipline of children commonly encountered in the hospital environment. The Child Abuse Task Force, a multidisciplinary group, along with key hospital administrators developed specific content for the policy, as well as marketing and educational materials. The No Hit Zone policy designates Kosair Children's Hospital as "an environment in which no adult shall hit a child, no adult shall hit another adult, no child shall hit an adult, and no child shall hit another child. When hitting is observed, it is everyone's responsibility to interrupt the behavior as well as communicate system policy to those present." Via a multidisciplinary, collaborative approach, the No Hit Zone was successfully implemented at Kosair Children's Hospital in 2012. Cost was nominal, and the support of key hospital administrators was critical to the program's success. Education of health professionals on de-escalation techniques and intervention with families at the early signs of parental stress occurred via live sessions and online training via case-based scenarios. The No Hit Zone is an important program used to provide a safe and caring environment for all families and staff of Kosair Children's Hospital. Demand for the program continues, demonstrated by the establishment of No Hit Zones at other local hospitals and multiple outpatient clinics. This article offers information for other organizations planning to conduct similar initiatives. Copyright © 2014 by the American Academy of Pediatrics.

SHIELD-HIT12A - a Monte Carlo particle transport program for ion therapy research

NASA Astrophysics Data System (ADS)

Bassler, N.; Hansen, D. C.; Lühr, A.; Thomsen, B.; Petersen, J. B.; Sobolevsky, N.

2014-03-01

Purpose: The Monte Carlo (MC) code SHIELD-HIT simulates the transport of ions through matter. Since SHIELD-HIT08 we added numerous features that improves speed, usability and underlying physics and thereby the user experience. The "-A" fork of SHIELD-HIT also aims to attach SHIELD-HIT to a heavy ion dose optimization algorithm to provide MC-optimized treatment plans that include radiobiology. Methods: SHIELD-HIT12A is written in FORTRAN and carefully retains platform independence. A powerful scoring engine is implemented scoring relevant quantities such as dose and track-average LET. It supports native formats compatible with the heavy ion treatment planning system TRiP. Stopping power files follow ICRU standard and are generated using the libdEdx library, which allows the user to choose from a multitude of stopping power tables. Results: SHIELD-HIT12A runs on Linux and Windows platforms. We experienced that new users quickly learn to use SHIELD-HIT12A and setup new geometries. Contrary to previous versions of SHIELD-HIT, the 12A distribution comes along with easy-to-use example files and an English manual. A new implementation of Vavilov straggling resulted in a massive reduction of computation time. Scheduled for later release are CT import and photon-electron transport. Conclusions: SHIELD-HIT12A is an interesting alternative ion transport engine. Apart from being a flexible particle therapy research tool, it can also serve as a back end for a MC ion treatment planning system. More information about SHIELD-HIT12A and a demo version can be found on http://www.shieldhit.org.

Monte Carlo studies on photon interactions in radiobiological experiments

PubMed Central

Shahmohammadi Beni, Mehrdad; Krstic, D.; Nikezic, D.

2018-01-01

X-ray and γ-ray photons have been widely used for studying radiobiological effects of ionizing radiations. Photons are indirectly ionizing radiations so they need to set in motion electrons (which are a directly ionizing radiation) to perform the ionizations. When the photon dose decreases to below a certain limit, the number of electrons set in motion will become so small that not all cells in an “exposed” cell population can get at least one electron hit. When some cells in a cell population are not hit by a directly ionizing radiation (in other words not irradiated), there will be rescue effect between the irradiated cells and non-irradiated cells, and the resultant radiobiological effect observed for the “exposed” cell population will be different. In the present paper, the mechanisms underlying photon interactions in radiobiological experiments were studied using our developed NRUphoton computer code, which was benchmarked against the MCNP5 code by comparing the photon dose delivered to the cell layer underneath the water medium. The following conclusions were reached: (1) The interaction fractions decreased in the following order: 16O > 12C > 14N > 1H. Bulges in the interaction fractions (versus water medium thickness) were observed, which reflected changes in the energies of the propagating photons due to traversals of different amount of water medium as well as changes in the energy-dependent photon interaction cross-sections. (2) Photoelectric interaction and incoherent scattering dominated for lower-energy (10 keV) and high-energy (100 keV and 1 MeV) incident photons. (3) The fractions of electron ejection from different nuclei were mainly governed by the photoelectric effect cross-sections, and the fractions from the 1s subshell were the largest. (4) The penetration fractions in general decreased with increasing medium thickness, and increased with increasing incident photon energy, the latter being explained by the corresponding reduction in interaction cross-sections. (5) The areas under the angular distribution curves of photons exiting the medium layer and subsequently undergoing interactions within the cell layer became smaller for larger incident photon energies. (6) The number of cells suffering at least one electron hit increased with the administered dose. For larger incident photon energies, the numbers of cells suffering at least one electron hit became smaller, which was attributed to the reduction in the photon interaction cross-section. These results highlighted the importance of the administered dose in radiobiological experiments. In particular, the threshold administered doses at which all cells in the exposed cell array suffered at least one electron hit might provide hints on explaining the intriguing observation that radiation-induced cancers can be statistically detected only above the threshold value of ~100 mSv, and thus on reconciling controversies over the linear no-threshold model. PMID:29561871

Frontal P300 decrement and executive dysfunction in adolescents with conduct problems.

PubMed

Kim, M S; Kim, J J; Kwon, J S

2001-01-01

This study investigated the cognitive and cerebral function of adolescents with conduct problems by neuropsychological battery (STIM) and event-related potential (ERP). Eighteen adolescents with conduct disorder, and 18 age-matched normal subjects were included. Such cognitive functions as attention, memory, executive function and problem solving were evaluated using subtests of STIM. ERP was measured using an auditory oddball paradigm. The conduct group showed a significantly lower hit rate on the Wisconsin Card Sorting Test (WCST) than the control group. In addition, the conduct group showed reduced P300 amplitude at Fz and Cz, and prolonged P300 latency at Fz, and there was a significant correlation between P300 amplitude and Stroop test performance. These results indicate that adolescents with conduct problems have impairments of executive function and inhibition, and that these impairments are associated with frontal dysfunction.

78 FR 29134 - HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-17

... quality, clinical operations, implementation, consumer technology, nationwide health information networks and privacy and security. Other groups will be convened to address specific issues as needed. HIT...) Direct the appropriate workgroup or other special group to develop a report for the HIT Standards...

42 CFR 495.332 - State Medicaid health information technology (HIT) plan requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 false State Medicaid health information technology (HIT... HEALTH RECORD TECHNOLOGY INCENTIVE PROGRAM Requirements Specific to the Medicaid Program § 495.332 State Medicaid health information technology (HIT) plan requirements. Each State Medicaid HIT plan must include...

42 CFR 495.332 - State Medicaid health information technology (HIT) plan requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 false State Medicaid health information technology (HIT... HEALTH RECORD TECHNOLOGY INCENTIVE PROGRAM Requirements Specific to the Medicaid Program § 495.332 State Medicaid health information technology (HIT) plan requirements. Each State Medicaid HIT plan must include...

42 CFR 495.332 - State Medicaid health information technology (HIT) plan requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 false State Medicaid health information technology (HIT... HEALTH RECORD TECHNOLOGY INCENTIVE PROGRAM Requirements Specific to the Medicaid Program § 495.332 State Medicaid health information technology (HIT) plan requirements. Each State Medicaid HIT plan must include...

42 CFR 495.332 - State Medicaid health information technology (HIT) plan requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 5 2011-10-01 2011-10-01 false State Medicaid health information technology (HIT... HEALTH RECORD TECHNOLOGY INCENTIVE PROGRAM Requirements Specific to the Medicaid Program § 495.332 State Medicaid health information technology (HIT) plan requirements. Each State Medicaid HIT plan must include...

77 FR 37408 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... be open to the public. Name of Committee: HIT Standards Committee. General Function of the Committee... with policies developed by the HIT Policy Committee. Date and Time: The meeting will be held on July 19...

77 FR 65691 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on November 13, 2012, from 9...

76 FR 70455 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on December 14, 2011, from 9...

76 FR 79684 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-22

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on January 25, 2012, from 9 a...

77 FR 65690 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on December 19, 2012, from 9...

77 FR 45353 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-31

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on August 15, 2012, from 9:00...

77 FR 2727 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on February 29, 2012, from 9...

77 FR 73661 - HIT Standards Committee Advisory Meetings; Notice of Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-11

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meetings; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: These meetings will be held on the following dates and...

77 FR 60438 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-03

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on October 17, 2012, from 9 a...

77 FR 50690 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-22

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on September 19, 2012, from 9...

42 CFR 495.332 - State Medicaid health information technology (HIT) plan requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false State Medicaid health information technology (HIT... HEALTH RECORD TECHNOLOGY INCENTIVE PROGRAM Requirements Specific to the Medicaid Program § 495.332 State Medicaid health information technology (HIT) plan requirements. Each State Medicaid HIT plan must include...

75 FR 62399 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-08

..., implementation, and privacy and security. HIT Standards Committee Schedule for the Assessment of HIT Policy... recommendations received from the HIT Policy Committee regarding health information technology standards...), section 3003. Erin Poetter, Office of Policy and Planning, Office of the National Coordinator for Health...

Robust estimation of adaptive tensors of curvature by tensor voting.

PubMed

Tong, Wai-Shun; Tang, Chi-Keung

2005-03-01

Although curvature estimation from a given mesh or regularly sampled point set is a well-studied problem, it is still challenging when the input consists of a cloud of unstructured points corrupted by misalignment error and outlier noise. Such input is ubiquitous in computer vision. In this paper, we propose a three-pass tensor voting algorithm to robustly estimate curvature tensors, from which accurate principal curvatures and directions can be calculated. Our quantitative estimation is an improvement over the previous two-pass algorithm, where only qualitative curvature estimation (sign of Gaussian curvature) is performed. To overcome misalignment errors, our improved method automatically corrects input point locations at subvoxel precision, which also rejects outliers that are uncorrectable. To adapt to different scales locally, we define the RadiusHit of a curvature tensor to quantify estimation accuracy and applicability. Our curvature estimation algorithm has been proven with detailed quantitative experiments, performing better in a variety of standard error metrics (percentage error in curvature magnitudes, absolute angle difference in curvature direction) in the presence of a large amount of misalignment noise.

Egypt western desert activity hits high gear

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

Petzet, G.A.

1996-11-04

Exploration in Egypt`s western desert is turning up large oil and gas reserves in several sub-basins. Though not a threat to the Gulf of Suez`s oil production dominance, the western desert`s output is climbing. And gas production is also set to rise as more pipelines are built. The paper describes the geology, Qarun field production, further exploration at Qarun and the Khalda/Obaiyed gas.

Remote Sensing Survey and Evaluation of the American Pass and Blue Point Chute Weirs, Atchafalaya Channel Training Project, Louisiana

DTIC Science & Technology

1989-06-01

Calhoun the Estrella and the Arizona. The Calhoun fired on the Queen of the West, hitting a steam line and setting her on fire. Soon after she exploded...of most of Taylor’s forces from the region, four Union gunboats, the Calhoun the Estrella the Arizona and the Clifton, steamed up the Atchafalaya

Move Over, SI: Minority Sports Magazine to Debut at Year's End

ERIC Educational Resources Information Center

Yates, Eleanor Lee

2004-01-01

A new magazine focusing exclusively on issues facing Black, Hispanic and other athletes of color is set to hit the news-stands at the end of the year. "The Color of Sports can fill a significant void and have a tremendous influence on shaping the agenda of the sports industry," says Aaron Brooks, one of the magazine's investors and quarterback for…

Speed of Sound in Metal Pipes: An Inexpensive Lab

ERIC Educational Resources Information Center

Huggins, Elisha

2008-01-01

Our favorite demonstration for sound waves is to set up a compressional pulse on a horizontally stretched Slinky[TM]. One can easily watch the pulse move back and forth at a speed of the order of one meter per second. Watching this demonstration, it occurred to us that the same thing might happen in a steel pipe if you hit the end of the pipe with…

Cheminformatics meets molecular mechanics: a combined application of knowledge-based pose scoring and physical force field-based hit scoring functions improves the accuracy of structure-based virtual screening.

PubMed

Hsieh, Jui-Hua; Yin, Shuangye; Wang, Xiang S; Liu, Shubin; Dokholyan, Nikolay V; Tropsha, Alexander

2012-01-23

Poor performance of scoring functions is a well-known bottleneck in structure-based virtual screening (VS), which is most frequently manifested in the scoring functions' inability to discriminate between true ligands vs known nonbinders (therefore designated as binding decoys). This deficiency leads to a large number of false positive hits resulting from VS. We have hypothesized that filtering out or penalizing docking poses recognized as non-native (i.e., pose decoys) should improve the performance of VS in terms of improved identification of true binders. Using several concepts from the field of cheminformatics, we have developed a novel approach to identifying pose decoys from an ensemble of poses generated by computational docking procedures. We demonstrate that the use of target-specific pose (scoring) filter in combination with a physical force field-based scoring function (MedusaScore) leads to significant improvement of hit rates in VS studies for 12 of the 13 benchmark sets from the clustered version of the Database of Useful Decoys (DUD). This new hybrid scoring function outperforms several conventional structure-based scoring functions, including XSCORE::HMSCORE, ChemScore, PLP, and Chemgauss3, in 6 out of 13 data sets at early stage of VS (up 1% decoys of the screening database). We compare our hybrid method with several novel VS methods that were recently reported to have good performances on the same DUD data sets. We find that the retrieved ligands using our method are chemically more diverse in comparison with two ligand-based methods (FieldScreen and FLAP::LBX). We also compare our method with FLAP::RBLB, a high-performance VS method that also utilizes both the receptor and the cognate ligand structures. Interestingly, we find that the top ligands retrieved using our method are highly complementary to those retrieved using FLAP::RBLB, hinting effective directions for best VS applications. We suggest that this integrative VS approach combining cheminformatics and molecular mechanics methodologies may be applied to a broad variety of protein targets to improve the outcome of structure-based drug discovery studies.

A Systolic Array-Based FPGA Parallel Architecture for the BLAST Algorithm

PubMed Central

Guo, Xinyu; Wang, Hong; Devabhaktuni, Vijay

2012-01-01

A design of systolic array-based Field Programmable Gate Array (FPGA) parallel architecture for Basic Local Alignment Search Tool (BLAST) Algorithm is proposed. BLAST is a heuristic biological sequence alignment algorithm which has been used by bioinformatics experts. In contrast to other designs that detect at most one hit in one-clock-cycle, our design applies a Multiple Hits Detection Module which is a pipelining systolic array to search multiple hits in a single-clock-cycle. Further, we designed a Hits Combination Block which combines overlapping hits from systolic array into one hit. These implementations completed the first and second step of BLAST architecture and achieved significant speedup comparing with previously published architectures. PMID:25969747

Informing the Selection of Screening Hit Series with in Silico Absorption, Distribution, Metabolism, Excretion, and Toxicity Profiles.

PubMed

Sanders, John M; Beshore, Douglas C; Culberson, J Christopher; Fells, James I; Imbriglio, Jason E; Gunaydin, Hakan; Haidle, Andrew M; Labroli, Marc; Mattioni, Brian E; Sciammetta, Nunzio; Shipe, William D; Sheridan, Robert P; Suen, Linda M; Verras, Andreas; Walji, Abbas; Joshi, Elizabeth M; Bueters, Tjerk

2017-08-24

High-throughput screening (HTS) has enabled millions of compounds to be assessed for biological activity, but challenges remain in the prioritization of hit series. While biological, absorption, distribution, metabolism, excretion, and toxicity (ADMET), purity, and structural data are routinely used to select chemical matter for further follow-up, the scarcity of historical ADMET data for screening hits limits our understanding of early hit compounds. Herein, we describe a process that utilizes a battery of in-house quantitative structure-activity relationship (QSAR) models to generate in silico ADMET profiles for hit series to enable more complete characterizations of HTS chemical matter. These profiles allow teams to quickly assess hit series for desirable ADMET properties or suspected liabilities that may require significant optimization. Accordingly, these in silico data can direct ADMET experimentation and profoundly impact the progression of hit series. Several prospective examples are presented to substantiate the value of this approach.

77 FR 15760 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on April 18, 2012, from 9 a.m...

77 FR 27459 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on June 20, 2012, from 9 a.m...

The impact of health information technology adoption by outpatient facilities on pregnancy outcomes.

PubMed

Deily, Mary E; Hu, Tianyan; Terrizzi, Sabrina; Chou, Shin-Yi; Meyerhoefer, Chad D

2013-02-01

Examine whether health information technology (HIT) at nonhospital facilities (NHFs) improves health outcomes and decreases resource use at hospitals within the same heath care network, and whether the impact of HIT varies as providers gain experience using the technologies. Administrative claims data on 491,832 births in Pennsylvania during 1998-2004 from the Pennsylvania Health Care Cost Containment Council and HIT applications data from the Dorenfest Institute. Fixed-effects regression analysis of the impact of HIT at NHFs on adverse birth outcomes and resource use. Greater use of clinical HIT applications by NHFs is associated with reduced incidence of obstetric trauma and preventable complications, as well as longer lengths of stay. In addition, the beneficial effects of HIT increase the longer that technologies have been in use. However, we find no consistent evidence on whether or how nonclinical HIT in NHFs affects either resource use or health outcomes. Clinical HIT applications at NHFs may reduce the likelihood of adverse birth outcomes, particularly after physicians and staff gain experience using the technologies. © Health Research and Educational Trust.

The Impact of Health Information Technology Adoption by Outpatient Facilities on Pregnancy Outcomes

PubMed Central

Deily, Mary E; Hu, Tianyan; Terrizzi, Sabrina; Chou, Shin-Yi; Meyerhoefer, Chad D

2013-01-01

Objective Examine whether health information technology (HIT) at nonhospital facilities (NHFs) improves health outcomes and decreases resource use at hospitals within the same heath care network, and whether the impact of HIT varies as providers gain experience using the technologies. Data Sources Administrative claims data on 491,832 births in Pennsylvania during 1998–2004 from the Pennsylvania Health Care Cost Containment Council and HIT applications data from the Dorenfest Institute. Study Design Fixed-effects regression analysis of the impact of HIT at NHFs on adverse birth outcomes and resource use. Principal Findings Greater use of clinical HIT applications by NHFs is associated with reduced incidence of obstetric trauma and preventable complications, as well as longer lengths of stay. In addition, the beneficial effects of HIT increase the longer that technologies have been in use. However, we find no consistent evidence on whether or how nonclinical HIT in NHFs affects either resource use or health outcomes. Conclusions Clinical HIT applications at NHFs may reduce the likelihood of adverse birth outcomes, particularly after physicians and staff gain experience using the technologies. PMID:22742682

Plasma exchange to remove HIT antibodies: dissociation between enzyme-immunoassay and platelet activation test reactivities.

PubMed

Warkentin, Theodore E; Sheppard, Jo-Ann I; Chu, F Victor; Kapoor, Anil; Crowther, Mark A; Gangji, Azim

2015-01-01

Repeated therapeutic plasma exchange (TPE) has been advocated to remove heparin-induced thrombocytopenia (HIT) IgG antibodies before cardiac/vascular surgery in patients who have serologically-confirmed acute or subacute HIT; for this situation, a negative platelet activation assay (eg, platelet serotonin-release assay [SRA]) has been recommended as the target serological end point to permit safe surgery. We compared reactivities in the SRA and an anti-PF4/heparin IgG-specific enzyme immunoassay (EIA), testing serial serum samples in a patient with recent (subacute) HIT who underwent serial TPE precardiac surgery, as well as for 15 other serially-diluted HIT sera. We observed that post-TPE/diluted HIT sera-when first testing SRA-negative-continue to test strongly positive by EIA-IgG. This dissociation between the platelet activation assay and a PF4-dependent immunoassay for HIT antibodies indicates that patients with subacute HIT undergoing repeated TPE before heparin reexposure should be tested by serial platelet activation assays even when their EIAs remain strongly positive. © 2015 by The American Society of Hematology.

Progress and Plans for the HIT--SI Experiment

NASA Astrophysics Data System (ADS)

Sieck, P. E.; Gu, P.; Hamp, W. T.; Izzo, V. A.; Jarboe, T. R.; Nelson, B. A.; O'Neill, R. G.; Redd, A. J.; Rogers, J. A.; Smith, R. J.

2002-11-01

The next step in the Helicity Injected Torus (HIT) program is HIT--SI, a ``bow tie'' spheromak to be formed and sustained by Steady Inductive Helicity Injection (SIHI). SIHI injects helicity at a nearly constant rate with no open field lines intersecting the boundary.(T. R. Jarboe, Fusion Technology 36) (1), p. 85, 1999 HIT--SI has been designed with a bow tie geometry to achieve stable high-β (>10%) spheromak equilibria.(U. Shumlak and T. R. Jarboe, Phys. Plasmas 7) (7), p. 2959, 2000 Injector dynamics depend greatly on reconnection rates in two locations: deep in the injector, and at the edge of the spheromak equilibrium. The first stage of HIT--SI operation concentrates on formation of a spheromak and sustainment for 1 ms, where the injector dynamics can be studied and the formation parameter space can be explored. Once these goals are met, the experiment will move into the second stage of operation, where the discharge duration will be extended and the device will inherit a suite of diagnostics from the existing HIT--II device.

An event-related potential study of memory for words spoken aloud or heard.

PubMed

Wilding, E L; Rugg, M D

1997-09-01

Subjects made old/new recognition judgements to visually presented words, half of which had been encountered in a prior study phase. For each word judged old, subjects made a subsequent source judgement, indicating whether they had pronounced the word aloud at study (spoken words), or whether they had heard the word spoken to them (heard words). Event-related potentials (ERPs) were compared for three classes of test item; words correctly judged to be new (correct rejections), and spoken and heard words that were correctly assigned to source (spoken hit/hit and heard hit/hit response categories). Consistent with previous findings (Wilding, E. L. and Rugg, M. D., Brain, 1996, 119, 889-905), two temporally and topographically dissociable components, with parietal and frontal maxima respectively, differentiated the ERPs to the hit/hit and correct rejection response categories. In addition, there was some evidence that the frontally distributed component could be decomposed into two distinct components, only one of which differentiated the two classes of hit/hit ERPs. The findings suggest that at least three functionally and neurologically dissociable processes can contribute to successful recovery of source information.

Factors associated with hit-and-run pedestrian fatalities and driver identification.

PubMed

MacLeod, Kara E; Griswold, Julia B; Arnold, Lindsay S; Ragland, David R

2012-03-01

As hit-and-run crashes account for a significant proportion of pedestrian fatalities, a better understanding of these crash types will assist efforts to reduce these fatalities. Of the more than 48,000 pedestrian deaths that were recorded in the United States between 1998 and 2007, 18.1% of them were caused by hit-and-run drivers. Using national data on single pedestrian-motor vehicle fatal crashes (1998-2007), logistic regression analyses were conducted to identify factors related to hit-and-run and to identify factors related to the identification of the hit-and-run driver. Results indicate an increased risk of hit-and-run in the early morning, poor light conditions, and on the weekend. There may also be an association between the type of victim and the likelihood of the driver leaving and being identified. Results also indicate that certain driver characteristics, behavior, and driving history are associated with hit-and-run. Alcohol use and invalid license were among the leading driver factor associated with an increased risk of hit-and-run. Prevention efforts that address such issues could substantially reduce pedestrian fatalities as a result of hit-and-run. However, more information about this driver population may be necessary. Copyright © 2011. Published by Elsevier Ltd.

Comparison of Video Head Impulse Test (vHIT) Gains Between Two Commercially Available Devices and by Different Gain Analytical Methods.

PubMed

Lee, Sang Hun; Yoo, Myung Hoon; Park, Jun Woo; Kang, Byung Chul; Yang, Chan Joo; Kang, Woo Suk; Ahn, Joong Ho; Chung, Jong Woo; Park, Hong Ju

2018-06-01

To evaluate whether video head impulse test (vHIT) gains are dependent on the measuring device and method of analysis. Prospective study. vHIT was performed in 25 healthy subjects using two devices simultaneously. vHIT gains were compared between these instruments and using five different methods of comparing position and velocity gains during head movement intervals. The two devices produced different vHIT gain results with the same method of analysis. There were also significant differences in the vHIT gains measured using different analytical methods. The gain analytic method that compares the areas under the velocity curve (AUC) of the head and eye movements during head movements showed lower vHIT gains than a method that compared the peak velocities of the head and eye movements. The former method produced the vHIT gain with the smallest standard deviation among the five procedures tested in this study. vHIT gains differ in normal subjects depending on the device and method of analysis used, suggesting that it is advisable for each device to have its own normal values. Gain calculations that compare the AUC of the head and eye movements during the head movements show the smallest variance.

Using information from historical high-throughput screens to predict active compounds.

PubMed

Riniker, Sereina; Wang, Yuan; Jenkins, Jeremy L; Landrum, Gregory A

2014-07-28

Modern high-throughput screening (HTS) is a well-established approach for hit finding in drug discovery that is routinely employed in the pharmaceutical industry to screen more than a million compounds within a few weeks. However, as the industry shifts to more disease-relevant but more complex phenotypic screens, the focus has moved to piloting smaller but smarter chemically/biologically diverse subsets followed by an expansion around hit compounds. One standard method for doing this is to train a machine-learning (ML) model with the chemical fingerprints of the tested subset of molecules and then select the next compounds based on the predictions of this model. An alternative approach would be to take advantage of the wealth of bioactivity information contained in older (full-deck) screens using so-called HTS fingerprints, where each element of the fingerprint corresponds to the outcome of a particular assay, as input to machine-learning algorithms. We constructed HTS fingerprints using two collections of data: 93 in-house assays and 95 publicly available assays from PubChem. For each source, an additional set of 51 and 46 assays, respectively, was collected for testing. Three different ML methods, random forest (RF), logistic regression (LR), and naïve Bayes (NB), were investigated for both the HTS fingerprint and a chemical fingerprint, Morgan2. RF was found to be best suited for learning from HTS fingerprints yielding area under the receiver operating characteristic curve (AUC) values >0.8 for 78% of the internal assays and enrichment factors at 5% (EF(5%)) >10 for 55% of the assays. The RF(HTS-fp) generally outperformed the LR trained with Morgan2, which was the best ML method for the chemical fingerprint, for the majority of assays. In addition, HTS fingerprints were found to retrieve more diverse chemotypes. Combining the two models through heterogeneous classifier fusion led to a similar or better performance than the best individual model for all assays. Further validation using a pair of in-house assays and data from a confirmatory screen--including a prospective set of around 2000 compounds selected based on our approach--confirmed the good performance. Thus, the combination of machine-learning with HTS fingerprints and chemical fingerprints utilizes information from both domains and presents a very promising approach for hit expansion, leading to more hits. The source code used with the public data is provided.

Fluence inhomogeneities due to a ripple filter induced Moiré effect.

PubMed

Ringbæk, Toke Printz; Brons, Stephan; Naumann, Jakob; Ackermann, Benjamin; Horn, Julian; Latzel, Harald; Scheloske, Stefan; Galonska, Michael; Bassler, Niels; Zink, Klemens; Weber, Uli

2015-02-07

At particle therapy facilities with pencil beam scanning, the implementation of a ripple filter (RiFi) broadens the Bragg peak, so fewer energy steps from the accelerator are required for a homogeneous dose coverage of the planning target volume (PTV). However, sharply focusing the scanned pencil beams at the RiFi plane by ion optical settings can lead to a Moiré effect, causing fluence inhomogeneities at the isocenter. This has been experimentally proven at the Heidelberg Ionenstrahl-Therapiezentrum (HIT), Universitätsklinikum Heidelberg, Germany. 150 MeV u(-1) carbon-12 ions are used for irradiation with a 3 mm thick RiFi. The beam is focused in front of and as close to the RiFi plane as possible. The pencil beam width is estimated to be 0.78 mm at a 93 mm distance from the RiFi. Radiographic films are used to obtain the fluence profile 30 mm in front of the isocenter, 930 mm from the RiFi. The Monte Carlo (MC) code SHIELD-HIT12A is used to determine the RiFi-induced inhomogeneities in the fluence distribution at the isocenter for a similar setup, pencil beam widths at the RiFi plane ranging from σχ(RiFi to 1.2 mm and for scanning step sizes ranging from 1.5 to 3.7 mm. The beam application and monitoring system (BAMS) used at HIT is modelled and simulated. When the width of the pencil beams at the RiFi plane is much smaller than the scanning step size, the resulting inhomogeneous fluence distribution at the RiFi plane interfers with the inhomogeneous RiFi mass distribution and fluence inhomogeneity can be observed at the isocenter as large as an 8% deviation from the mean fluence. The inverse of the fluence ripple period at the isocenter is found to be the difference between the inverse of the RiFi period and the inverse of the scanning step size. We have been able to use MC simulations to reproduce the spacing of the ripple stripes seen in films irradiated at HIT. Our findings clearly indicate that pencil beams sharply focused near the RiFi plane result in fluence inhomogeneity at the isocenter. In the normal clinical application, such a setting should generally be avoided.

Think of HIT.

PubMed

Warkentin, Theodore E

2006-01-01

Heparin-induced thrombocytopenia, or HIT, can present in many ways, ranging from common-isolated thrombocytopenia, venous thromboembolism, acute limb ischemia-to less common but specific presentations-necrotizing skin lesions at heparin injection sites, post-bolus acute systemic reactions, and adrenal hemorrhagic necrosis (secondary to adrenal vein thrombosis). Many patients with HIT have mild or moderate thrombocytopenia: the median platelet count nadir is 60 x 10(9)/L, and ranges from 15 to 150 x 10(9)/L in 90% of patients, most of whom evince a 50% or greater fall in the platelet count. HIT that begins after stopping heparin ("delayed-onset HIT") is increasingly recognized. Factors influencing risk of HIT include type of heparin (unfractionated heparin > low-molecular-weight heparin), type of patient (surgical > medical), and gender (female > male). Since timely diagnosis and treatment of HIT may reduce the risk of adverse outcomes, this review focuses on those clinical circumstances that should prompt the clinician to "think of HIT." Coumarin anticoagulants such as warfarin are ineffective in acute HIT and can even be deleterious by predisposing to micro-thrombosis via protein C depletion (venous limb gangrene and skin necrosis syndromes). Thus, it is important to avoid or postpone coumarin while managing HIT hypercoagulability, focusing on agents that inhibit thrombin directly (lepirudin, argatroban) or that inhibit its generation (danaparoid, fondaparinux). Post-marketing experience suggests that standard dosing of lepirudin is too high; current recommendations are to avoid the initial lepirudin bolus and to begin with lower infusion rates, even in patients without overt renal dysfunction.

Prospective evaluation of automatized PF4/heparin immunoassays HemosIL HIT-ab (PF4-H) for the diagnosis of heparin-induced thrombocytopenia.

PubMed

Jourdy, Y; Nougier, C; Rugeri, L; Bordet, J C; Sobas, F; Negrier, C

2015-04-01

Recently, rapid immunoassays have been developed to allow the detection of antibodies anti-PF4/heparin. In this prospective study, we evaluated the performances of a automatized immunoassay (HemosIL HIT-Ab) in comparison with an ELISA (Zymutest HIA IgG) used for the diagnosis of heparin-induced thrombocytopenia (HIT) in association with the 4T's score. According to the 4T's score, samples with score ≤3 had no further analysis. Two immunological assays Zymutest HIA IgG and HemosIL HIT-Ab were performed in samples with score ≥4. In patients with at least one positive immunological assay or two negative immunological assays but with high-pretest probability (4T's score ≥6), HIT was screened by one functional assay using washed platelets. The sensitivities of both assays were excellent and comparable (100%). The specificity was 92.3% for ELISA and 91.2% for HemosIL HIT-Ab. The analysis of the operating characteristics showed that both assays have almost identical ROCs (AUROC, 0.9951 and 0.9853, respectively, for ELISA and HemosIL HIT-Ab) and the calculating of the κ coefficient revealed a good agreement (0.67). Performance characteristics of the HemosIL HIT-Ab are comparable to the Zymutest HIA IgG. The HemosIL HIT-Ab can be used in association with the 4T's score to rule out HIT. © 2014 John Wiley & Sons Ltd.

Reliability and Validity of the Persian HIT-6 Questionnaire in Migraine and Tension-type Headache.

PubMed

Zandifar, Alireza; Banihashemi, Mahboobeh; Haghdoost, Faraidoon; Masjedi, Samaneh S; Manouchehri, Navid; Asgari, Fatemeh; Najafi, Mohammad R; Ghorbani, Abbas; Zandifar, Samaneh; Saadatnia, Mohammad; White, Michelle K

2014-09-01

Headache Impact Test (HIT-6) measures the impact headaches in a 1-month period. We validated the Persian translation of HIT-6, compared the HIT-6 psychometric analysis between migraine and tension-type headache (TTH) patients, and evaluated the capability of HIT-6 to differentiate between TTH, chronic migraine, and episodic migraine. Qualified participants, including 274 patients diagnosed with migraine or TTH, were required to complete HIT-6, SF-36v2, and a symptoms questionnaire on their first visit. At 3 and 8 weeks from first visit, participants completed HIT-6. Internal consistency (Cronbach's α) and test-retest reproducibility (Pearson's correlation coefficient) were used to assess reliability. Convergent validity was also assessed. Tension-type headache, episodic, and chronic migraines included 24.5%, 61.9%, and 13.6% of the participants, respectively. Internal consistency among all patients, TTH, and migraine in the first visit were 0.74, 0.77, and 0.73, respectively. Test-retest reliability for HIT-6 between visit 1 and 2 showed a moderate level of correlation (r = 0.50). Convergent validity and also item total correlation were acceptable. There was no significant difference in HIT-6 total score between TTH and migraine. Persian HIT-6 is a valid and reliable questionnaire for the evaluation of headache. However, it cannot differentiate between chronic migraine, episodic migraine, and TTH in Iranian population. © 2013 World Institute of Pain.

The role of health information technology in advancing care management and coordination in accountable care organizations.

PubMed

Wu, Frances M; Shortell, Stephen M; Rundall, Thomas G; Bloom, Joan R

To be successful, accountable care organizations (ACOs) must effectively manage patient care. Health information technology (HIT) can support care delivery by providing various degrees of coordination. Few studies have examined the role of HIT functionalities or the role of different levels of coordination enabled by HIT on care management processes. We examine HIT functionalities in ACOs, categorized by the level of coordination they enable in terms of information and work flow, to determine which specific HIT functionalities and levels of coordination are most strongly associated with care management processes. Retrospective cross-sectional analysis was done using 2012 data from the National Survey of Accountable Care Organizations. HIT functionalities are categorized into coordination levels: information capture, the lowest level, which coordinates through standardization; information provision, which supports unidirectional activities; and information exchange, which reflects the highest level of coordination allowing for bidirectional exchange. The Care Management Process index (CMP index) includes 13 questions about the extent to which care is planned, monitored, and supported by providers and patients. Multiple regressions adjusting for organizational and ACO contractual factors are used to assess relationships between HIT functionalities and the CMP index. HIT functionality coordinating the most complex interdependences (information exchange) was associated with a 0.41 standard deviation change in the CMP index (β = .41, p < .001), but the associations for information capture (β = -.01, p = .97) and information provision (β = .15, p = .48) functionalities were not significant. The current study has shed some light on the relationship between HIT and care management processes by specifying the coordination roles that HIT may play and, in particular, the importance of information exchange functionalities. Although these represent early findings, further research can help policy makers and clinical leaders understand how to prioritize HIT development given resource constraints.

Heparin-induced thrombocytopenia: reducing misdiagnosis via collaboration between an inpatient anticoagulation pharmacy service and hospital reference laboratory.

PubMed

Burnett, Allison E; Bowles, Harmony; Borrego, Matthew E; Montoya, Tiffany N; Garcia, David A; Mahan, Charles

2016-11-01

Misdiagnosis of heparin-induced thrombocytopenia (HIT) is common and exposes patients to high-risk therapies and potentially serious adverse events. The primary objective of this study was to evaluate the impact of collaboration between an inpatient pharmacy-driven anticoagulation management service (AMS) and hospital reference laboratory to reduce inappropriate HIT antibody testing via pharmacist intervention and use of the 4T pre-test probability score. Secondary objectives included clinical outcomes and cost-savings realized through reduced laboratory testing and decreased unnecessary treatment of HIT. This was a single center, pre-post, observational study. The hospital reference laboratory contacted the AMS when they received a blood sample for an enzyme-linked immunosorbent HIT antibody (HIT Ab). Trained pharmacists prospectively scored each HIT Ab ordered by using the 4T score with subsequent communication to physicians recommending for or against processing and reporting of lab results. Utilizing retrospective chart review and a database for all patients with a HIT Ab ordered during the study period, we compared the incidence of HIT Ab testing before and after implementation of the pharmacy-driven 4T score intervention. Our intervention significantly reduced the number of inappropriate HIT Ab tests processed (176 vs. 63, p < 0.0001), with no increase in thrombotic or hemorrhagic events. Overall incidence of suspected and confirmed HIT was <3 and <0.005 %, respectively. Overall cost savings were $75,754 (US) or 62 % per patient exposed to heparin between the pre and post intervention groups. Collaboration between inpatient pharmacy AMS and hospital reference laboratories can result in reduction of misdiagnosis of HIT and significant cost savings with similar safety.

Increased Health Information Technology Adoption and Use Among Small Primary Care Physician Practices Over Time: A National Cohort Study.

PubMed

Rittenhouse, Diane R; Ramsay, Patricia P; Casalino, Lawrence P; McClellan, Sean; Kandel, Zosha K; Shortell, Stephen M

2017-01-01

Implementation and meaningful use of health information technology (HIT) has been shown to facilitate delivery system transformation, yet implementation is far from universal. This study examined correlates of greater HIT implementation over time among a national cohort of small primary care practices in the United States. We used data from a 40-minute telephone panel survey of 566 small primary care practices having 8 or fewer physicians to investigate adoption and use of HIT in 2007-2010 and 2012-2013. We used generalized estimating equations (GEE) to estimate the association of practice characteristics and external incentives with the adoption and use of HIT. We studied 18 measures of HIT functionalities, including record keeping, clinical decision support, patient communication, and health information exchange with hospitals and pharmacies. Overall, use of 16 HIT functionalities increased significantly over time, whereas use of 2 decreased significantly. On average, compared with physician-owned practices, hospital-owned practices used 1.48 (95% CI, 1.07-1.88; P <.001) more HIT processes. And relative to smaller practices, practices with 3 to 8 physicians used 2.49 (95% CI, 2.26-2.72; P <.001) more HIT processes. Participation in pay-for-performance programs, participation in public reporting of clinical quality data, and a larger proportion of revenue from Medicare were also associated with greater adoption and use of HIT. The new Medicare Access and CHIP Reauthorization Act (MACRA) will provide payment incentives and technical support to speed HIT adoption and use by small practices. We found that external incentives were, indeed, positively associated with greater adoption and use of HIT. Our findings also support a strategy of targeting assistance to smaller physician practices and those that are physician owned. © 2017 Annals of Family Medicine, Inc.

The costs of heparin-induced thrombocytopenia: a patient-based cost of illness analysis.

PubMed

Wilke, T; Tesch, S; Scholz, A; Kohlmann, T; Greinacher, A

2009-05-01

SUMMARY BACKGROUND AND OBJECTIVES: Due to the complexity of heparin-induced thrombocytopenia (HIT), currently available cost analyses are rough estimates. The objectives of this study were quantification of costs involved in HIT and identification of main cost drivers based on a patient-oriented approach. Patients diagnosed with HIT (1995-2004, University-hospital Greifswald, Germany) based on a positive functional assay (HIPA test) were retrieved from the laboratory records and scored (4T-score) by two medical experts using the patient file. For cost of illness analysis, predefined HIT-relevant cost parameters (medication costs, prolonged in-hospital stay, diagnostic and therapeutic interventions, laboratory tests, blood transfusions) were retrieved from the patient files. The data were analysed by linear regression estimates with the log of costs and a gamma regression model. Mean length of stay data of non-HIT patients were obtained from the German Federal Statistical Office, adjusted for patient characteristics, comorbidities and year of treatment. Hospital costs were provided by the controlling department. One hundred and thirty HIT cases with a 4T-score >or=4 and a positive HIPA test were analyzed. Mean additional costs of a HIT case were 9008 euro. The main cost drivers were prolonged in-hospital stay (70.3%) and costs of alternative anticoagulants (19.7%). HIT was more costly in surgical patients compared with medical patients and in patients with thrombosis. Early start of alternative anticoagulation did not increase HIT costs despite the high medication costs indicating prevention of costly complications. An HIT cost calculator is provided, allowing online calculation of HIT costs based on local cost structures and different currencies.

The use and role of open source software applications in public and not-for-profit hospitals in the United States.

PubMed

Vest, Joshua R; Stephens, James H

2013-01-01

The potential cost savings and customizability of open source software (OSS) may be particularly attractive for hospitals. However, numerous health-care-specific OSS applications exist, the adoption of OSS health information technology (HIT) applications is not widespread in the United States. This disconnect between the availability of promising software and low adoption raises the basic question: If OSS HIT is so advantageous, why are more health care organizations not using it? We interviewed the chief information officer, or equivalent position, at 17 not-for-profit and public hospitals across the United States. Through targeted recruitment, our sample included nine hospitals using OSS HIT and eight hospitals not using OSS HIT. The open-ended interview questions were guided by domains included in the fit-viability theory, an organizational-level innovation adoption framework, and those suggested by a review of the literature. Transcripts were analyzed using an inductive and comparative approach, which involved an open coding for relevant themes. Interviews described the state of OSS use in hospitals. Specifically, general OSS applications were widely used by IT professionals. In addition, hospitals using OSS HIT still relied heavily on vendor support. In terms of why decisions arose to use OSS HIT, several hospitals using OSS HIT noted the cost advantages. In contrast, hospitals avoiding OSS HIT were clear, OSS as a class did not fit with clinical work and posed too much risk. Perceptions of OSS HIT ranged from enthusiastic embracement to resigned adoption, to refusal, to abandonment. Some organizations were achieving success with their OSS HIT choices, but they still relied on vendors for significant support. The decision to adopt OSS HIT was not uniform but contingent upon views of the risk posed by the technology, economic factors, and the hospital's existing capabilities.

Recovery of Vestibulo-Ocular Reflex Symmetry After an Acute Unilateral Peripheral Vestibular Deficit: Time Course and Correlation With Canal Paresis.

PubMed

Allum, John H J; Cleworth, T; Honegger, Flurin

2016-07-01

We investigated how response asymmetries and deficit side response amplitudes for head accelerations used clinically to test the vestibular ocular reflex (VOR) are correlated with caloric canal paresis (CP) values. 30 patients were examined at onset of an acute unilateral peripheral vestibular deficit (aUPVD) and 3, 6, and 13 weeks later with three different VOR tests: caloric, rotating chair (ROT), and video head impulse tests (vHIT). Response changes over time were fitted with an exponential decay model and compared with using linear regression analysis. Recovery times (to within 10% of steady state) were similar for vHIT-asymmetry and CP (>10 weeks) but shorter for ROT asymmetry (<4 weeks). Regressions with CP were similar (vHIT asymmetry, R = 0.68, ROT, R = 0.62). Responses to the deficit side were also equally well correlated with CP values (R = 0.71). Specificity for vHIT and 20 degrees/s ROT deficit side responses was 100% in comparison to CP values, sensitivity was 74% for vHIT, 75% for ROT. A decrease in normal side responses occurred for ROT but not for vHIT at 3 weeks. Normal side responses were weekly correlated with CP for ROT (R = 0.49) but not for vHIT (R = 0.17). These results indicate that vHIT deficit side VOR gains are slightly better correlated with CP values than ROT, probably because of similar recovery time courses of vHIT and caloric responses and the lack of normal side vHIT changes. However, specificity and sensitivity is the same for vHIT and ROT tests.

High-Intensity Interval Training with Vibration as Rest Intervals Attenuates Fiber Atrophy and Prevents Decreases in Anaerobic Performance

PubMed Central

Mueller, Sandro Manuel; Aguayo, David; Zuercher, Matthias; Fleischmann, Oliver; Boutellier, Urs; Auer, Maria; Jung, Hans H.; Toigo, Marco

2015-01-01

Aerobic high-intensity interval training (HIT) improves cardiovascular capacity but may reduce the finite work capacity above critical power (W′) and lead to atrophy of myosin heavy chain (MyHC)-2 fibers. Since whole-body vibration may enhance indices of anaerobic performance, we examined whether side-alternating whole-body vibration as a replacement for the active rest intervals during a 4x4 min HIT prevents decreases in anaerobic performance and capacity without compromising gains in aerobic function. Thirty-three young recreationally active men were randomly assigned to conduct either conventional 4x4 min HIT, HIT with 3 min of WBV at 18 Hz (HIT+VIB18) or 30 Hz (HIT+VIB30) in lieu of conventional rest intervals, or WBV at 30 Hz (VIB30). Pre and post training, critical power (CP), W′, cellular muscle characteristics, as well as cardiovascular and neuromuscular variables were determined. W′ (−14.3%, P = 0.013), maximal voluntary torque (−8.6%, P = 0.001), rate of force development (−10.5%, P = 0.018), maximal jumping power (−6.3%, P = 0.007) and cross-sectional areas of MyHC-2A fibers (−6.4%, P = 0.044) were reduced only after conventional HIT. CP, V̇O2peak, peak cardiac output, and overall capillary-to-fiber ratio were increased after HIT, HIT+VIB18, and HIT+VIB30 without differences between groups. HIT-specific reductions in anaerobic performance and capacity were prevented by replacing active rest intervals with side-alternating whole-body vibration, notably without compromising aerobic adaptations. Therefore, competitive cyclists (and potentially other endurance-oriented athletes) may benefit from replacing the active rest intervals during aerobic HIT with side-alternating whole-body vibration. Trial Registration ClinicalTrials.gov Identifier: NCT01875146 PMID:25679998

Carrier transport and sensitivity issues in heterojunction with intrinsic thin layer solar cells on N-type crystalline silicon: A computer simulation study

NASA Astrophysics Data System (ADS)

Rahmouni, M.; Datta, A.; Chatterjee, P.; Damon-Lacoste, J.; Ballif, C.; Roca i Cabarrocas, P.

2010-03-01

Heterojunction with intrinsic thin layer or "HIT" solar cells are considered favorable for large-scale manufacturing of solar modules, as they combine the high efficiency of crystalline silicon (c-Si) solar cells, with the low cost of amorphous silicon technology. In this article, based on experimental data published by Sanyo, we simulate the performance of a series of HIT cells on N-type crystalline silicon substrates with hydrogenated amorphous silicon (a-Si:H) emitter layers, to gain insight into carrier transport and the general functioning of these devices. Both single and double HIT structures are modeled, beginning with the initial Sanyo cells having low open circuit voltages but high fill factors, right up to double HIT cells exhibiting record values for both parameters. The one-dimensional numerical modeling program "Amorphous Semiconductor Device Modeling Program" has been used for this purpose. We show that the simulations can correctly reproduce the electrical characteristics and temperature dependence for a set of devices with varying I-layer thickness. Under standard AM1.5 illumination, we show that the transport is dominated by the diffusion mechanism, similar to conventional P/N homojunction solar cells, and tunneling is not required to describe the performance of state-of-the art devices. Also modeling has been used to study the sensitivity of N-c-Si HIT solar cell performance to various parameters. We find that the solar cell output is particularly sensitive to the defect states on the surface of the c-Si wafer facing the emitter, to the indium tin oxide/P-a-Si:H front contact barrier height and to the band gap and activation energy of the P-a-Si:H emitter, while the I-a-Si:H layer is necessary to achieve both high Voc and fill factor, as it passivates the defects on the surface of the c-Si wafer. Finally, we describe in detail for most parameters how they affect current transport and cell properties.

"Hit-and-Run" transcription: de novo transcription initiated by a transient bZIP1 "hit" persists after the "run".

PubMed

Doidy, Joan; Li, Ying; Neymotin, Benjamin; Edwards, Molly B; Varala, Kranthi; Gresham, David; Coruzzi, Gloria M

2016-02-03

Dynamic transcriptional regulation is critical for an organism's response to environmental signals and yet remains elusive to capture. Such transcriptional regulation is mediated by master transcription factors (TF) that control large gene regulatory networks. Recently, we described a dynamic mode of TF regulation named "hit-and-run". This model proposes that master TF can interact transiently with a set of targets, but the transcription of these transient targets continues after the TF dissociation from the target promoter. However, experimental evidence validating active transcription of the transient TF-targets is still lacking. Here, we show that active transcription continues after transient TF-target interactions by tracking de novo synthesis of RNAs made in response to TF nuclear import. To do this, we introduced an affinity-labeled 4-thiouracil (4tU) nucleobase to specifically isolate newly synthesized transcripts following conditional TF nuclear import. Thus, we extended the TARGET system (Transient Assay Reporting Genome-wide Effects of Transcription factors) to include 4tU-labeling and named this new technology TARGET-tU. Our proof-of-principle example is the master TF Basic Leucine Zipper 1 (bZIP1), a central integrator of metabolic signaling in plants. Using TARGET-tU, we captured newly synthesized mRNAs made in response to bZIP1 nuclear import at a time when bZIP1 is no longer detectably bound to its target. Thus, the analysis of de novo transcripomics demonstrates that bZIP1 may act as a catalyst TF to initiate a transcriptional complex ("hit"), after which active transcription by RNA polymerase continues without the TF being bound to the gene promoter ("run"). Our findings provide experimental proof for active transcription of transient TF-targets supporting a "hit-and-run" mode of action. This dynamic regulatory model allows a master TF to catalytically propagate rapid and broad transcriptional responses to changes in environment. Thus, the functional read-out of de novo transcripts produced by transient TF-target interactions allowed us to capture new models for genome-wide transcriptional control.